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Background: Recent research highlighted the potential role of circulating cell-free DNA (cfDNA), resulted by apoptosis or cell necrosis, as a prognostic marker in the setting of different clinical conditions. Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Apoptosis of renal epithelial cells is proposed as a mechanism involved in CRS type 1. In this study, we investigated cfDNA levels in patients with acute heart failure (AHF) and CRS type 1 and the possible correlation between cfDNA levels and inflammatory and apoptotic parameters. Methods: We enrolled 17 AHF patients and 15 CRS type 1 who exhibited AKI at the time of admission (caused by AHF) or developed AKI during the first 48 h from admission. cfDNA was extracted from plasma and quantified by real-time polymerase chain reaction. Plasma levels of NGAL, tumor necrosis factor-α, interleukin (IL)-6, IL-18, and caspase-3 were measured. Results: We observed significantly higher levels of cfDNA in patients with CRS type 1 than patients with AHF. Caspase-3, IL-6, IL-18, and NGAL levels resulted significantly increased in patients with CRS type 1. Moreover, a positive correlation between cfDNA levels and caspase-3 levels was found, as well as between cfDNA levels and IL-6 and renal parameters. Conclusion: Our study explores the premise of cfDNA as a marker for apoptosis and inflammation in CRS type 1 patients. cfDNA could potentially serve as an index for noninvasive monitoring of tissue damage and apoptosis in patients with AKI induced by AHF.

We report the case of an adult patient, affected by complete transposition of great arteries with ventricular septal defect, who survived until 68 years of age without surgery, thanks to the presence of a common atrium and pulmonary stenosis. (Level of Difficulty: Advanced.), Graphical abstract, We report a case of an adult patient, affected by complete transposition of great arteries with ventricular septal defect, who survived until…

The XVth Banff Conference on Allograft Pathology meeting was held on September 23-27, 2019, in Pittsburgh, Pennsylvania, USA. During this meeting, two main topics in cardiac transplant pathology were addressed: (a) Improvement of endomyocardial biopsy (EMB) accuracy for the diagnosis of rejection and other significant injury patterns, and (b) the orphaned lesion known as Quilty effect or nodular endocardial infiltrates. Molecular technologies have evolved in recent years, deciphering pathophysiology of cardiac rejection. Diagnostically, it is time to integrate the histopathology of EMBs and molecular data. The goal is to incorporate molecular pathology, performed on the same paraffin block as a companion test for histopathology, to yield more accurate and objective EMB interpretation. Application of digital image analysis from hematoxylin and eosin (H&E) stain to multiplex labeling is another means of extracting additional information from EMBs. New concepts have emerged exploring the multifaceted significance of myocardial injury, minimal rejection patterns supported by molecular profiles, and lesions of arteriolitis/vasculitis in the setting of T cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR). The orphaned lesion known as Quilty effect or nodular endocardial infiltrates. A state-of-the-art session with historical aspects and current dilemmas was reviewed, and possible pathogenesis proposed, based on advances in immunology to explain conflicting data. The Quilty effect will be the subject of a multicenter project to explore whether it functions as a tertiary lymphoid organ.

Amyloidosis is a group of progressive and devastating disorders resulting from misfolded proteins extracellular deposition into tissues. When deposition of fibrils occurs in cardiac tissues, this systemic disease can lead to a very poor prognosis. In this review, we focused on the most common types of cardiac amyloidosis and their treatments. Early diagnosis remains critically important, and here we reviewed the diagnostic methods adopted starting from the non-invasive imaging techniques to more invasive approaches, and the typing of precursor proteins. Typing the different misfolding proteins is mandatory since therapy differs accordingly and thus guiding therapy. We highlighted the most updated and recent treatment strategies to cure amyloidosis.

Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury. In this study, we evaluate the role of lipopolysaccharide (LPS) and various inflammatory markers in the developing acute kidney injury (AKI) in acute heart failure (AHF) patients. We enrolled 31 AHF patients and 20 CRS type 1 (the cause of AKI was presumed to be related to cardiac dysfunction) and 17 healthy volunteers without AHF, AKI or CKD, as control group (CTR). We assessed levels of LPS, proinflammatory cytokines (TNF-α, IL-6, IL-18), and oxidative stress marker (myeloperoxidase, MPO). We observed a significant increase in LPS, TNF-α, IL-6, IL-18 and MPO levels in CRS type 1 and AHF group compared to CTR. LPS levels resulted significantly higher in CRS type 1 patients compared with AHF (118.2 pg/mL, IQR 77.8–217.6 versus 13.5 pg/mL, IQR 12.0–17.0, p = 0.008). We found a cytokines and oxidative stress dysregulation in CRS type 1 patients compared with AHF. Furthermore, we observed a strong positive significant correlation between LPS levels and IL-6 (Spearman’s rho = 0.79, p

Background Melkersson–Rosenthal syndrome (MRS) is a rare, neuro-mucocutaneous disease which presents as orofacial swelling, facial palsy and fissured tongue. These symptoms may occur simultaneously or, more frequently, with a oligosymptomatic or monosymptomatic pattern. Swelling, that is the most common initial finding, may mimic hereditary or acquired angioedema, a disorder caused by histamine or bradykinin-mediated plasma-leakage affecting subcutaneous and/or submucosal tissue. The differential diagnosis of MRS includes also chronic inflammatory and infective diseases characterized by granulomatous infiltration, as well as rosacea, contact dermatitis, allergic reactions and Bell’s palsy. Case presentation A 71-year old, non-allergic female patient with no familial and personal history of angioedema presented, a few days after a possible herpes simplex or varicella-zoster virus infection, with monolateral facial paraesthesia and lower lip edema. After temporary remission of symptoms on oral steroids and antihistamines, she showed swelling recurrence refractory to valaciclovir therapy and a subsequent course of antihistamines. The clinical picture and a previous history of non-Hodgkin lymphoma prompted us to rule out an acquired form of paraneoplastic, C1-inhibitor (C1-INH) deficiency: C1q and both antigen and functional C1-INH tested normal, whilst we found low plasma levels of C3 and C4 possibly related to the parallel detection of antiphospholipid antibodies. Thus, we hypothesized a non-histaminergic, idiopathic form of angioedema and planned further therapy with tranexamic acid and the leukotriene receptor antagonist montelukast. Treatment failure with both drugs finally suggested a Melkersson–Rosenthal syndrome, which was confirmed by histologic findings of non caseating granulomas on lip biopsy. Conclusion Melkersson–Rosenthal syndrome may occur with rather non-specific symptoms and overlap with alternative conditions, including recurrent angioedema. No specific biomarkers for MRS exist and clinical diagnosis is often of exclusion. The finding of complement or immune alterations, as in our patient, may be further confounding and justify the need for skin or mucosal biopsy to establish a correct diagnosis and prescribe targeted therapy.

Background and Aims Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in older white adults, with an incidence of 12 cases per millions of people per year. Primary MN (PMN, 75%-80% of MNs) is an organ-specific autoimmune disease caused by antibodies anti-PLA2R and anti-THSD7A. Regardless of treatment one third of patients progresses to end-stage renal disease and two third develop non-progressive chronic kidney disease. Renal biopsy is the gold standard for MN diagnosis. Several clinical and biochemical markers have been associated with the risk of progressive loss of kidney function while contrasting results have been obtained by the few studies which have examined the prognostic value of histologic findings. In this study the clinical outcome of patients with PMN has been considered based on the prognostic value of histological findings. Method Forty-nine patients with PMN of our Nephrology Unit at Padova University Hospital from 2003 to 2018 were considered. 16 patients were excluded from the study due to missing data. Age, comorbidities, proteinuria (g/day) and renal function (eGFR, CKD-EPI) were collected. eGFR decline and decrease of proteinuria were used as clinical outcomes. The follow-up was considered from renal biopsy to the last visit (in absence of GFR decline or decrease in proteinuria). Histological grading (0-3) was assigned to parameters (glomerulosclerosis (GS), tubular atrophy (TA), interstitial fibrosis (IF), vascular hyalinosis (VH)) and were evaluated separately or in combination (as GSTIV score). Morphometric analysis was used to quantify IF and expressed in percentage as the mean of area covered by pixel. Statistical analysis was performed using Fisher’s exact test and Mann-Whitney U-test where appropriate. Cox regression analyses (univariate and multivariate) were performed to identify variables associated with both renal outcomes and p ROC curves were used to determine interstitial fibrosis cut-off values predictive for both outcomes. Area under the curve (AUC) between 0.8 and 1.0 was considered as significant. Diagnostic accuracy was assessed by Specificity (Sp), Sensibility (Se), positive (PPV) and negative (NPV) predictive values and positive (LR+) and negative (LR-) likelihood ratios. Results Patients with no decrease of proteinuria had a greater degree of IF vs those with a full response (p=0.006). Univariate Cox analyses identified age ≥65 years (HR 4.92), pre-existing CKD (HR 12.98) and IF (HR3.05) as significant predictors of renal function decline in all patients. Multivariate Cox analysis confirmed these variables (age ≥65 years HR 3.05, CKD HR 6.35, IF HR 3.03). In patients without CKD only IF was significantly associated with eGFR decline in both Cox univariate and multivariate analysis (HR 4.34 and 5.05 respectively). ROC analysis showed that IF threshold of 17.80% identified patients with eGFR reduction (AUC 0.65, Se 0.50, Sp 0.79, PPV 0.75, NPV 0.45, LR+ 2.38, LR-0.63) and IF threshold of 18.04% the lack of proteinuria reduction (AUC 0.78, Se 0.70, Sp 0.83, PPV 0.67, NPV 0.80, LR+ 4.12, LR- 0.36). Conclusion Our study shows that IF could be used as a histologic predictor of renal and proteinuria outcomes. Biopsy report should therefore also include quantitative IF data that could be helpful for the choice of a more appropriate therapeutic approach.

The AAOMS in 2014 changed from BRONJ to the term Medication-Related Osteonecrosis of the Jaw (MRONJ), because of the growing number of osteonecrosis cases associated with other antiresorptive and antiangiogenic therapies. Even if the drugs involved are different, the histopathological findings are the same. Colonies of Actinomyces are encountered in most cases. The aim of the present study is to report on Actinomyces prevalence among the cases of MRONJ, taking into consideration also antiresorptive and antiangiogenic therapies in the literature and in our sample between 2005 and 2020. The review was performed using the database Medline the linkage between Actinomyces infection and MRONJ. The retrospective study was conducted on patients between with clinical and radiological manifestations of MRONJ May 2005 and February 2020. A total of 42 articles were found, 30 publications have been taken into consideration for the review. A total of 114 patients have been examined at the Padua Hospital. A total of 101 oncological patients presented the histological confirmation of MRONJ. 83 specimens revealed the presence of Actinomyces infection (82.18%). Actinomyces-associated lesions are frequent and present a wide spectrum of clinical manifestation.

Hypertrophic cardiomyopathy (HCM) and primary restrictive cardiomyopathy (RCM) have a similar genetic background as they are both caused mainly by variants in sarcomeric genes. These “sarcomeric cardiomyopathies” also share diastolic dysfunction as the prevalent pathophysiological mechanism. Starting from the observation that patients with HCM and primary RCM may coexist in the same family, a characteristic pathophysiological profile of HCM with restrictive physiology has been recently described and supports the hypothesis that familiar forms of primary RCM may represent a part of the phenotypic spectrum of HCM rather than a different genetic cardiomyopathy. To further complicate this scenario some infiltrative (amyloidosis) and storage diseases (Fabry disease and glycogen storage diseases) may show either a hypertrophic or restrictive phenotype according to left ventricular wall thickness and filling pattern. Establishing a correct etiological diagnosis among HCM, primary RCM, and hypertrophic or restrictive phenocopies is of paramount importance for cascade family screening and therapy.

Aim of the study was to evaluate the efficacy and safety of sectorial bone resection with piezoelectric device in patients with STAGE 1 and 2 (SIPMO/SICMF) ONJ. Materials and methods: A retrospective study was conducted in cancer and osteometabolic patients with ONJ of Stage 1 or Stage 2 according to SIPMO/SICMF 2.0 who underwent to sectorial bone resection with piezoelectric device and contextual first intention closure.All procedures were performed in local anesthesia and conscious sedation, in out-patients clinical setting.Treatment was considered efficient in case of complete epithelization of the site, complete resolution of symptoms and absence of exposure of bone. Piezoelectric device was used without other rotating handpieces.All patients were followed up at 2 weeks, 8 weeks and 6 months after the surgery.Results: 10 patients, from 45 to 83 (average 68.4) years old, 7 females and 3 males, were identified.Bisphosphonates were administrated in 7 cases (zoledronate) for oncological reasons, 2 patients for osteometabolic reasons (1 alendronate, 1 hybandronate) while in 1 case for algodystrophy (an off-label use of clodronate).8 mandibular sectorial osteotomies and 2 maxillary were performed, with a single recurrence.3 patients were heavy smokers: this surprising did not compromise the outcome.Conclusions: According to our case studies the use of piezoelectric device in sectorial bone resection in ONJ seem to be effective and easy to use.

We report five cases of sudden intrauterine death due to premature closure of the ductus arteriosus. In four cases, this was caused by dissecting the hematoma of the ductus arteriosus with intimal flap and obliteration of the lumen. In one case, the ductus arteriosus was aneurysmatic, with lumen occlusion caused by thrombus stratification. No drug therapy or free medication consumption were reported during pregnancy. The time of stillbirth ranged between 26 and 33 gestational weeks. We performed TUNEL analysis for apoptosis quantification. The dissecting features were intimal tears with flap formation in four of the cases, just above the origin of the ductus arteriosus from the pulmonary artery. The dissecting hematoma of the ductus arteriosus extended downward to the descending aorta and backward to the aortic arch with involvement of the left carotid and left subclavian arteries. TUNEL analysis showed a high number of apoptotic smooth muscle cells in the media in two cases. Abnormal ductal remodeling with absence of subintimal cushions, lacunar spaces rich in glycosaminoglycans (cystic medial necrosis), and smooth muscle cell apoptosis were the pathological substrates accounting for failure of remodeling process and dissection.

Cardiac allograft rejection following heart transplantation is challenging to diagnose. Tissue biopsies are the gold standard in monitoring the different types of rejection. The last decade has seen an increased emphasis on identifying non-invasive methods to improve rejection diagnosis and overcome tissue biopsy invasiveness. Liquid biopsy, as an efficient non-invasive diagnostic and prognostic oncological monitoring tool, seems to be applicable in heart transplant follow-ups. Moreover, molecular techniques applied on blood can be translated to tissue samples to provide novel perspectives on tissue and reveal new diagnostic and prognostic biomarkers. This review aims to provide a comprehensive overview of the state-of-the-art of the new methodologies in cardiac allograft rejection monitoring and investigate the future perspectives on invasive and non-invasive rejection biomarkers identification. We reviewed literature from the most used scientific databases, such as PubMed, Google Scholar, and Scopus. We extracted 192 papers and, after a selection and exclusion process, we included in the review 81 papers. The described limitations notwithstanding, this review show how molecular biology techniques and omics science could be deployed complementarily to the histopathological rejection diagnosis on tissue biopsies, thus representing an integrated approach for heart transplant patients monitoring.

The IPCCC is a standardized international system of paediatric and congenital cardiac nomenclature that should be used in all registries, databases and research studies in the domain of paediatric and congenital cardiac care, including those related to HLHS. This recommendation is level 1 class C [15, 16, 700]. Multi-institutional databases and registries allow benchmarking of data concerning death, patterns of practice, morbidity and postoperative length of stay [540]. As a level 1 class C recommendation, all paediatric and congenital cardiac teams should routinely assess their own data against national and international benchmarks using multi-institutional databases and registries [540, 697–699, 701].

In the complex pathogenesis of vitiligo, the exact mechanism of the dermatosis is still to be clarified. We previously demonstrated that a protein called melanoma inhibitory activity (MIA) is present in non-segmental vitiligo skin and seems to cause the detachment of melanocytes, consequently creating the depigmented macules. In this study, we present an animal model of vitiligo on the basis of the ability of the MIA protein to induce vitiligo-like lesions. Twenty pigmented mice were chosen for the experiments and received injections in the tail with saline (control group) or with saline + MIA protein (treated group). The control group did not show any sign of depigmentation. The treated group showed, instead, clear zones of complete depigmentation in the injected areas in each mouse, with the appearance of white patches with whitening of the hair and a clear-cut edge. Histological examination of the tail in the treated zone showed the absence of melanocytes, without the presence of any inflammatory cell or any sign of skin inflammation patterns, confirming the detachment of the melanocyte operated by the MIA protein. These data seem to confirm a possible role played by the MIA protein in the pathogenesis of vitiligo and may support the development of treatments able to inhibit its action as an alternative therapeutic strategy for this disorder.

Background: Circulating extracellular vesicles (EVs) are raising considerable interest as a non-invasive diagnostic tool, as they are easily detectable in biologic fluids and contain a specific set of nucleic acids, proteins, and lipids reflecting pathophysiologic conditions. We aimed to investigate differences in plasma-derived EV surface protein profiles as a biomarker to be used in combination with endomyocardial biopsies (EMBs) for the diagnosis of allograft rejection. Methods: Plasma was collected from 90 patients (53 training cohort, 37 validation cohort) before EMB. EV concentration was assessed by nanoparticle tracking analysis. EV surface antigens were measured using a multiplex flow cytometry assay composed of 37 fluorescently labeled capture bead populations coated with specific antibodies directed against respective EV surface epitopes. Results: The concentration of EVs was significantly increased and their diameter decreased in patients undergoing rejection as compared with negative ones. The trend was highly significant for both antibody-mediated rejection and acute cellular rejection (p < 0.001). Among EV surface markers, CD3, CD2, ROR1, SSEA-4, human leukocyte antigen (HLA)-I, and CD41b were identified as discriminants between controls and acute cellular rejection, whereas HLA-II, CD326, CD19, CD25, CD20, ROR1, SSEA-4, HLA-I, and CD41b discriminated controls from patients with antibody-mediated rejection. Receiver operating characteristics curves confirmed a reliable diagnostic performance for each single marker (area under the curve range, 0.727-0.939). According to differential EV-marker expression, a diagnostic model was built and validated in an external cohort of patients. Our model was able to distinguish patients undergoing rejection from those without rejection. The accuracy at validation in an independent external cohort reached 86.5%. Its application for patient management has the potential to reduce the number of EMBs. Further studies in a higher number of patients are required to validate this approach for clinical purposes. Conclusions: Circulating EVs are highly promising as a new tool to characterize cardiac allograft rejection and to be complementary to EMB monitoring.

Introduction and objectives: SerpinB3 is a cysteine protease inhibitor involved in several biological activities. It is progressively expressed in chronic liver disease, but not in normal liver. The role in vascular reactivity of this serpin, belonging to the same family of Angiotensin II, is still unknown. Our aim was to evaluate the in vivo and in vitro effects of SerpinB3 on systemic and splanchnic hemodynamics. Material and methods: Different hemodynamic parameters were evaluated by ultrasonography in two colonies of mice (transgenic for human SerpinB3 and C57BL/6J controls) at baseline and after chronic carbon tetrachloride (CCl4) treatment. In vitro SerpinB3 effect on mesenteric microvessels of 5 Wistar-Kyoto rats was analyzed measuring its direct action on: (a) preconstricted arteries, (b) dose–response curves to phenylephrine, before and after inhibition of angiotensin II type 1 receptors with irbesartan. Hearts of SerpinB3 transgenic mice and of the corresponding controls were also analyzed by morphometric assessment. Results: In SerpinB3 transgenic mice, cardiac output (51.6 ± 21.5 vs 30.1 ± 10.8 ml/min, p = 0.003), hepatic artery pulsatility index (0.85 ± 0.13 vs 0.65 ± 0.11, p

The objective of this study was to perform a quantitative analysis and to identify predictors of embolic filter debris (EFD) load during carotid artery stenting (CAS) in asymptomatic patients.All patients with asymptomatic carotid stenosis70% undergoing CAS between 2008 and 2016 were included in a prospective database. A distal filter protection device was used in all patients. At the end of the procedure, the filter was fixed in formalin and then analyzed with a stereomicroscope. Morphometric analysis was performed with Image-Pro Plus software (Media Cybernetics, Rockville, Md). The total area of the filter membrane and the area covered by particulate material were quantified. The quantity of membrane occupied by debris was expressed as percentage of covered surface area. Anatomic and clinical variables were evaluated for their association with EFD load using multiple logistic regression.Among the 278 patients undergoing CAS, an open-cell stent was implanted in 211 patients (76%); 67 patients (24%) received a closed-cell stent. Overall technical success and clinical success were both 99%; no perioperative death was reported. Stroke rate was 1.8% (major, n = 1 [0.4%]; minor, n = 4 [1.4%]); transient ischemic attacks occurred in 5% of cases (n = 14). The quantitative analysis of the filter revealed that EFD was present in 74% of cases (n = 207). The mean EFD load was 10% of the filter surface (median, 1; range, 0-80); it was 10% in 203 patients (73%), between 11% and 20% in 39 patients (14%), between 21% and 30% in 14 patients (5%), and31% in 22 (8%). Patients with any type of ischemic neurologic event after CAS (stroke and transient ischemic attack) had a significantly higher mean EFD load compared with uneventful cases (26.7% ± 19.0% vs 8.5% ± 13.5%; P .001). The observational frequency distribution analysis identified the presence of12.5% EFD load as the optimal cutoff for the association with clinically relevant perioperative ischemic events (sensitivity, 78%; specificity, 77%; area under the curve, 0.81). The multivariate analysis demonstrated that age75 years (odds ratio [OR], 2.56; P = .003), pre-existing ipsilateral ischemic cerebral lesions (OR, 2.09; P = .047), hypoechogenic plaque on the preoperative duplex ultrasound examination (OR, 6.05; P .001), and plaque length15 mm (OR, 1.79; P = .049) were independent predictors of EFD load12.5%.The majority of asymptomatic carotid stenoses treated with CAS have detectable embolic debris in the protecting filter. Age75 years, pre-existing ipsilateral cerebral ischemic lesions, hypoechogenic plaque, and plaque length15 mm should be taken into consideration as independent predictors of clinically relevant embolic debris during the procedure.

R2* cardiac magnetic resonance (CMR) allows the non-invasive measurement of myocardial iron. We calibrated cardiac R2* values against myocardial tissue–measured iron concentration by using a segmental approach and we assessed the iron distribution. Five hearts of thalassemia patients were donated after death/transplantation to the CoreLab of the Myocardial Iron Overload in Thalassemia Network. A multislice multiecho R2* approach was adopted. After CMR, used as guidance, the heart was cut in three short-axis slices and each slice was cut into different equiangular segments according to AHA segmentation and differentiated into endocardial and epicardial layers. Tissue iron concentration was measured by atomic absorption spectrometer technique. Fifty-five samples were used since only for two hearts all the 16 samples were analyzed. Mean iron concentration was 4.71 ± 4.67 mg/g dw. Segmental iron levels ranged from 0.24 to 13.78 mg/g dw. The coefficient of variability of iron for myocardial segments ranged from 8.08 to 24.54% (mean 13.49 ± 6.93%). Iron concentration was significantly higher in the epicardial than in the endocardial layer (5.99 ± 6.01 vs 4.84 ± 4.87 mg/g dw; p = 0.042). Four different circumferential regions (anterior, septal, inferior, and lateral) were defined. A circumferential heterogeneity was noted, with more iron in the anterior region, followed by the inferior region. The direct nonlinear fitting of R2* and [Fe] data led to the calibration curve: [Fe] = 0.0022 ∙ (R2*-ROI)1.462 (R-square = 0.956). Our data further validate R2* CMR using a segmental approach as a sensitive and early technique for quantifying iron distribution in the current clinical practice. • Calibration in humans for cardiovascular magnetic resonance R2* against myocardial iron concentration was provided. • A circumferential heterogeneity in cardiac iron distribution was detected: more iron was observed in the anterior region, followed by the inferior region. This finding corroborates the use of a segmental T2* CMR approach in the clinical practice to detect a heterogeneous iron distribution. • The comparison between the cardiac T2* values obtained with the region-based and the pixel-wise approaches showed a significant correlation and no significant difference but, in presence of significant iron load, the region-based approach resulted in significantly higher T2* values.

Purpose Circulating extracellular vesicles (EVs) are raising considerable interest as a non-invasive diagnostic tool.We aimed to investigate differences in plasma-derived EV surface protein profiles as a biomarker to be used in combination with endomyocardial biopsies (EMBs) for the diagnosis of allograft rejection. Methods Plasma was collected from 90 patients (53 training cohort, 37 validation cohort) before EMB. EV concentration was assessed by nanoparticle tracking analysis. EV surface antigens were measured using a multiplex flow cytometry assay composed of 37 fluorescently labeled capture bead populations coated with specific antibodies directed against respective EV surface epitopes. According to differential EV-markers expression two diagnostic model were built and validated through supervised learning algorithms (linear discriminant analysis-LDA- and random forest model- RF) Results The concentration of EVs was significantly increased and their diameter decreased in patients undergoing rejection as compared with negative ones. The trend was highly significant for both antibody-mediated rejection and acute cellular rejection (p Conclusion Circulating EVs are highly promising as a new tool to characterize cardiac allograft rejection and to be complementary to EMB monitoring

Purpose The aim of the study was to evaluate the trend of all the three type of rejection, cellular, humoral and mixed, during 6 years of follow-up , from 2012 to 2017 at the our transplant center, to evaluate pre-transplant clinical predictive factors for acute rejections and mortality. Methods We evaluated 149 patients heart transplanted adult patients transplanted from January 2012 and December 2017 at the university of Padua . Post transplant monitoring EMBs from 2012 to December 2018 were reevaluated . All the pre-transplant clinical were collected in a data base. The statistical analysis was subdivided in two parts. In the first part we analyzed the trend of the three different type of rejections, calculated the rate expressed as a average number of rejections for patients per year, with a Poisson distribution. In the second part we applied Machine learning method (ML), and algorithm Random Forest (RF) to analyzed the pre-transplant factors for the onset of acute rejections and for mortality. Results Of the 149 pts , 108(72,5%) were male and 41 (27,5%) female, mean age at transplantation 53,7±11,9 years for male and 46,2±15,4 for female. Two thousand and thirty three EMBs were performed during follow up with a mean number of 13,5±4,27 EMBs per patient. Of these , 1163 (57,2%) were negative for rejection, 31 (1,5%) positive for humoral rejection (pAMR+), 796 (39,2%) positive for ACR , 43 (2,1%) positive for mixed rejection. For all type of rejection there were a decreasing trend during the 6 years of follow up. The reduction in the mean number of rejection was 53,4% for acute rejection. Pre transplant predictive factors of cellular rejection were the pathology leading to heart transplant with a predictive value of 0,9%, age at transplant with a value of 0,8%. For humoral rejection the predictive factors were preforming antibodies anti HLA class II with a predictive value of 1,9%, previous pregnancies and miscarriage with a predictive value of 1,8% . The risk of mortality was influenced by age of donor with a risk value of 7,8%, the age at transplant with a risk value of 6,6%. Conclusion We have demonstrated that there is a decreasing trend of the three types of rejection during the last 6 years of follow up, in particular of cellular rejection. This is not in relation with changing in immunosuppressive drugs , but probably is due to pre and postoperative better management of heart transplant patients.

Purpose Vasculitis had been considered a histopathological marker in severe form of both cellular and humoral rejection. However, in mild forms of rejections, it has not been considered a diagnostic and prognostic histopathologic criterion. Aim of this study is to assess clinical relevance of vasculitis, in terms of mortality and cardiac allograft vasculopathy development, in the mild forms of rejection in heart transplanted patients. Methods We reviewed 2794 monitoring endomyocardial biopsies from 170 adult heart transplanted pts at our center. On endomyocardial biopsies, we evaluated the presence of vasculitis in the different types of rejection . Clinical data were collected during follow up. A Multi-State Markov model was applied to describe the rejection dynamic profile and hazard for mortality, persistence of rejection and CAV development.. We used as reference population the registry data of patients who underwent HTX from 2004 to 2018 provided by the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry Results Vasculitis was detected in 442 endomyocardial biopsies ( 442/2794, 15,8%) with an incremental percent distribution according to the severity of rejection. In ACR, vasculitis significantly increased the risk of mortality by 9% (HR [95% CI]: 1.09; [1.00-1.18]) the hazard of mortality if the patient was negative for ACR and by 14% (HR [95% CI]: 1.14; [1.02-1.37], if the patients was negative for ACR, and by 14% in a mild form of rejection (1R). Similar results were obtained for pAMR and mixed rejection. In ACR, pAMR and mixed rejection patients with vasculitis have a shorter life expectancy than patients without with a loss of four months at ten year follow up for ACR, and of 9 months for pAMR and mixed rejection. Conclusion Vasculitis when present, independently from the grade and type of rejection, carries a negative prognostic value. The worse histopathological feature was represented by the association of pAMR+ACR and vasculitis.

The Fontan operation is the current surgical procedure to treat single-ventricle congenital heart disease, by splitting the systemic and pulmonary circulations and thus permitting lifespan to adulthood for the majority of newborns. However, emerging data are showing that Fontan-associated liver disease (FALD) is an increasing related cause of morbidity and mortality in patients with the Fontan circuit. We described the clinical, laboratory, and transient elastography (TE) findings in a case series of adults with the Fontan circuit, and also correlated data with post-mortem histological features, aimed to define the prognostic value of TE in the staging of FALD. All patients presented signs of a long-standing Fontan failure, characterized by reoperation need, systemic ventricle dysfunction, and FALD stigmata (liver and spleen enlargement, portal vein and inferior vena cava dilation, and abnormal liver function tests). Liver and spleen stiffness (LS and SS) values were indicative of significant liver fibrosis/cirrhosis and the presence of suggestive portal hypertension (LS mean 35.9; range 27.3–44.7 kPa; SS mean 42.1, range 32.2–54.5 kPa). Post-mortem evaluations confirmed a gross hepatic architecture distortion in all cases. All patients died from severe complications related to liver dysfunction and bleeding. TE correlated well with pathological findings and FALD severity. We propose this validated and harmless technique to monitor liver fibrosis extension and portal hypertension over time in Fontan patients, and to identify the optimal timing for surgical reoperations or orthotopic-heart transplantation (OHT), avoiding a higher risk of morbidity and mortality in cases with severe FALD.

Background: Hypertrophic cardiomyopathy (HCM) is characterized by myocardial disarray, small vessel disease (SVD), and fibrosis. The relationship between SVD and replacement-type fibrosis is still unclear. Methods: Histopathologic assessment of replacement-type fibrosis and SVD in HCM patients with either end-stage heart failure (HF) or sudden cardiac death (SCD). Chronic ischemic heart disease (IHD) patients served as controls. Results: Forty HCM hearts, 10 HF and 30 SCD, were studied. Replacement-type fibrosis was detected in all HF and in 57% of SCD cases. In SCD, replacement-type fibrosis was associated with older age, greater septal thickness, SVD prevalence, and score (all p &lt, 0.05). Prevalence of SVD did not show significant differences among SCD, HF, and IHD (73%, 100% and 95%, respectively), while SVD score was higher in HF than IHD and SCD (2.4, 1.95, and 1.18, respectively) and in areas with replacement-type fibrosis vs. those without in HF (3.4 vs. 1.4) and SCD (1.4 vs. 0.8) (all p &lt, 0.05). Conclusions: SVD is a frequent feature in HCM independent of the clinical presentation. A higher SVD score is observed in HCM-HF and in areas with replacement-type fibrosis. Although SVD is part of the HCM phenotype, further remodeling of the microcirculation might occur secondarily to fibrosis.

The 13th Banff Conference on Allograft Pathology was held in Vancouver, British Columbia, Canada from October 5 to 10, 2015. The cardiac session was devoted to current diagnostic issues in heart transplantation with a focus on antibody‐mediated rejection (AMR) and small vessel arteriopathy. Specific topics included the strengths and limitations of the current rejection grading system, the central role of microvascular injury in AMR and approaches to semiquantitative assessment of histopathologic and immunophenotypic indicators, the role of AMR in the development of cardiac allograft vasculopathy, the important role of serologic antibody detection in the management of transplant recipients, and the potential application of new molecular approaches to the elucidation of the pathophysiology of AMR and potential for improving the current diagnostic system. Herein we summarize the key points from the presentations, the comprehensive, open and wide‐ranging multidisciplinary discussion that was generated, and considerations for future endeavors., This article summarizes the Banff conference on heart transplantation with a focus on antibody‐mediated rejection, strengths and limitations of the current rejection grading system, the important role of serologic antibody detection and the potential application of new molecular approaches to the elucidation of the pathophysiology of antibody‐mediated rejection, and the potential for improving the current diagnostic system. See the companion report on page 28.

Cardiomyopathies with excessive trabeculations, often labelled as ‘left ventricular non-compaction’, can lead to complications, including heart failure, life-threatening heart rhythm disturbances, and cardiac emboli. The main patho-anatomical substrate is increased cardiac trabeculations. Cardiac imaging can depict the location and extent of trabeculations in the ventricle. Cardiovascular magnetic resonance is increasingly requested to confirm or exclude cardiomyopathy with excessive trabeculations when clinically suspected or in patients with a known family history. The ‘non-compaction-to-compaction ratio’ and the trabecular mass are the two most commonly used diagnostic approaches that have good diagnostic accuracy when used in patients with an intermediate pre-test probability. Increased trabeculations in the context of a low pre-test probability, and no other cardiac abnormalities considered associated with this cardiomyopathy, appear benign and may not represent disease.

We investigated the effects of human amniotic fluid stem cells (hAFS) and rat adipose tissue stromal vascular fraction GFP-positive cells (rSVC-GFP) in a model of cardio-renal syndrome type II (CRSII).RHF was induced by monocrotaline (MCT) in 28 Sprague-Dawley rats. Three weeks later, four million hAFS or rSVC-GFP cells were injected via tail vein. BNP, sCreatinine, kidney and heart NGAL and MMP9, sCytokines, kidney and heart apoptosis and cells (Cs) engraftment were evaluated. Cell-treated rats showed a significant reduction of serum NGAL and Creatinine compared to CRSII. In both hAFS and rSVC-GFP group, kidney protein expression of NGAL was significantly lower than in CRSII (hAFS p = 0.036 and rSVC-GFP p 0.0001) and similar to that of controls. In both hAFS and rSVC-GFP treated rats, we observed cell engraftment in the medulla and differentiation into tubular, endothelial and SMCs cells. Apoptosis was significantly decreased in cell-treated rats (hAFS 14.07 ± 1.38 and rSVC-GFP 12.67 ± 2.96 cells/mmCell therapy produced improvement in kidney function in rats with CRSII. This was the result of interstitial, vessel and tubular cell engraftment leading to tubular and vessel regeneration, decreased tubular cells apoptosis and mitigated pro-inflammatory milieu. Reduction of NGLA-MMP9 complexes mainly due to decrease MMPs activity prevented further negative heart remodeling.

This multicenter case-controlled pilot study evaluated myocardial inflammatory burden (IB) and phenotype in endomyocardial biopsies (EMBs) with and without pathologic antibody-mediated rejection (pAMR). Sixty-five EMBs from five European heart transplant centers were centrally reviewed as positive (grade 2, n = 28), suspicious (grade 1, n = 7) or negative (n = 30) for pAMR. Absolute counts of total, intravascular (IV) and extravascular (EV) immunophenotyped mononuclear cells were correlated with pAMR grade, capillary C4d deposition, donor specific antibody (DSA) status and acute cellular rejection (ACR). In pAMR+ biopsies, equivalent number of IV CD3+ T lymphocytes (23 ± 4/0.225 mm(2) ) and CD68+ macrophages (21 ± 4/0.225 mm(2) ) were seen. IB and cell phenotype correlated with pAMR grade, C4d positivity and DSA positivity (p < 0.0001). High numbers of IV T lymphocytes were associated with low grade ACR (p = 0.002). In late-occurring AMR EV plasma cells occurring in 34% of pAMR+ EMBs were associated with higher IB. The IB in AMR correlated with pAMR+, C4d positivity and DSA positivity. In pAMR+ equivalent numbers of IV T lymphocytes and macrophages were found. The presence of plasma cells was associated with a higher IB and occurrence of pAMR late after transplantation.

Light chain amyloidosis is characterized by the progressive deposition of immunoglobulin light chains into the extracellular tissue, leading to organ dysfunction. Usually, it is associated with an underlying clonal plasma cell dyscrasia and rarely with chronic lymphocytic leukaemia. Herein, we described the first report of a patient with relapsed chronic lymphocytic leukaemia harbouring TP53 abnormalities who developed, histologically proven, systemic light chain amyloidosis who was treated with the PI3K inhibitor, idelalisib, and rituximab. Unfortunately, the patient had sudden death during sleep, likely caused by arrhythmia secondary to amyloid cardiomyopathy. Idelalisib was at least effective in reducing secretory free light chain, chronic lymphocytic leukaemia burden, and to improve the survival of patient.

Pulmonary hypertension (PH) is a haemodynamic and pathophysiological disorder associated with a variety of cardiovascular and respiratory conditions, including congenital heart disease (CHD). In this Chapter, we discuss the definition and pathophysiology of pulmonary arterial hypertension (PAH) related to CHD (PAH-CHD) and its evolution, from Victor Eisenmenger’s first report, to its systematic description by Paul Wood. We focus not only on lung histopathology, but also describe current knowledge on cardiac adaptation to PH and the effect of PAH on the large pulmonary arteries. Finally, we introduce the concept of operability of cardiac defects in the presence of PAH and describe current recommendations for identifying PAH-CHD patients who may benefit from repair of their defect, as opposed to those in whom the defect should not be closed.

Objectives This study sought to evaluate the safety and performance of the Igaki-Tamai (Igaki Medical Planning Company, Kyoto, Japan) biodegradable stent in patients with occlusive superficial femoral artery (SFA) disease. Background Poly-L-lactic acid (PLLA) biodegradable stents have been shown to be effective in the coronaries, but no data are available regarding their efficacy in the femoral artery. Methods A prospective, multicenter, nonrandomized study enrolled 30 patients with symptomatic de novo SFA disease undergoing implantation of Igaki-Tamai bioresorbable stents. Clinical examinations and duplex ultrasound were prospectively performed after 1, 6, 9, and 12 months. The main study endpoints were technical success, restenosis rate, rate of target lesion revascularization (TLR), changes in ankle-brachial index (ABI), and quality of life by evaluating the walking impairment questionnaire (WIQ). Safety was assessed by monitoring the occurrence of major adverse clinical events and serious adverse events. Results The mean age of the patients was 67.7 years, and 77% were male. The mean lesion length was 5.9 cm. Mean diameter stenosis was reduced from 89.9% to 6.2%, after stent implantation. Technical success was 96.7%. Binary restenosis rate for the 6 and 12 months follow-up was 39.3% and 67.9%, respectively. The TLR rate was 25.0% after 6 months and 57.1% after 12 months. All TLR were successful; the secondary patency rate after 1 year was 89.3%. Between baseline and 12 months, ABI increased in 53.6% of patients. Functional endpoints (WIQ), even if affected by a relatively high reintervention rate, showed improvement in most of the patients. Conclusions The GAIA (Evaluation of the Biodegradable Peripheral Igaki-Tamai Stent in the Treatment of De Novo Lesions in the Superficial Femoral Artery) study shows that when using biodegradable PLLA stents (Igaki-Tamai), the immediate angiographic results are comparable to the results of metal stents, achieving a high secondary patency rate after 1 year. Modifications of stent characteristics and technical modifications are needed with the goal to reduce the restenosis rate during the reabsorption period.

Giant cell myocarditis (GCM) is a very aggressive form of myocardial inflammation. While immunosuppressive therapy is usually able to keep under control the disease and prolong the average transplant-free survival in many patients, effective therapeutic strategies to prevent or treat the recurrence of GCM in transplanted organs are still to be defined. We report the case of a young woman with idiopathic GCM who, despite immediate aggressive immunosuppressive therapy, rapidly progressed to irreversible heart failure and required urgent heart transplantation. Yet, 2 months later, the disease recurred in the transplanted heart, despite an intensive four-drug antirejection regimen. The introduction of rituximab, an anti-CD20 monoclonal antibody, 375 mg/m(2) /week i.v. for four consecutive weeks and then every 4 months as maintenance therapy, determined a complete and steady clinical remission of the disease. After nineteen months since rituximab administration, the patient is doing well and repeated follow-up endo-myocardial biopsies confirmed the complete resolution of myocardial inflammation. Our experience seems to suggest that rituximab can be a reasonably effective and safe therapeutic option in GCM recurring in transplanted organs.

Cardiac allograft vasculopathy is regarded as a progressive and diffuse intimal hyperplastic lesion of arteries and veins that leads to insidious vessel narrowing and to allograft ischemic disease, such as acute myocardial infarction or sudden cardiac death. The coronary lesions in transplanted hearts are considered as a particular type of arteriosclerosis with many similarities but also significant differences compared to native coronary atherosclerosis. It is particularly difficult for pathologists to systematically classify the lesions and to elucidate their origins, since over time, the allograft immune responses cause vascular pathology characterized by not only the onset of de novo fibrocellular lesions but also remodeling of already-existing native atherosclerotic lesions in the donor heart. Intraplaque hemorrhages, which result from newly formed leaky microvessels, may cause rapid increase of stenosis and generate a substrate for plaque destabilization. Comparing cardiac allograft vasculopathy from explanted hearts at autopsy with native coronary atherosclerosis from hearts removed at transplantation has revealed that ongoing intraplaque hemorrhages are also an important feature of cardiac allograft vasculopathy and may be important factors in the rapid progression of cardiac allograft vasculopathy.

Objective Although the management of carotid disease is well established for symptomatic lesions ≥70%, the surgical treatment for a symptomatic ≤50% stenosis is not supported by data from randomized trials. Factors other than lumen narrowing, such as plaque instability, seem to be involved in cerebral and retinal ischemic events. This study analyzes the early-term and long-term outcomes of carotid endarterectomy (CEA) performed in patients with low-grade (≤50% on North American Symptomatic Carotid Endarterectomy Trial criteria) symptomatic carotid stenosis. Methods The study involves 57 consecutive patients undergoing CEA for symptomatic low-grade carotid disease at our institution over 5 years, and 21 (36.8%) had experienced more than one ischemic event. Overall, 48 (84.2%) had a minor stroke, and nine (15.8%) had an episode of retinal ischemia. Diagnosis was made by a vascular neurologist based on an ultrasound examination combined with noninvasive imaging studies, after ruling out other possible causes of embolization. Before CEA, all patients were receiving antiplatelet treatment, and 87% were taking statins. All patients underwent eversion CEA under general deep anesthesia, with selective shunting. All carotid plaques were examined histologically. Long-term follow-up (median, 28 months; mean, 32 ± 5 months; range, 3-56 months) was obtained for 55 patients. Results No 30-day strokes or deaths occurred, and no patients had recurrent neurologic events related to the revascularized hemisphere during the follow-up. No late carotid occlusions were detected, but one asymptomatic moderate restenosis was documented. There were seven late deaths (12.7%), none of which were stroke-related. Survival rates were 98% at 1 year and 90% at 3 years. All removed carotid plaques showed different features of ulceration or rupture, with underlying hemorrhage associated with a thrombus. Conclusions This study shows that CEA is a safe, effective, and durable treatment for patients with symptomatic low-grade carotid stenosis associated with unstable plaque. Patients had excellent protection against further ischemic events and survived long enough to justify the initial surgical risk. Plaque instability seems to play a major part in the onset of ischemic events, regardless the entity of lumen narrowing.

During the last 25 years, antibody-mediated rejection of the cardiac allograft has evolved from a relatively obscure concept to a recognized clinical complication in the management of heart transplant patients. Herein we report the consensus findings from a series of meetings held between 2010-2012 to develop a Working Formulation for the pathologic diagnosis, grading, and reporting of cardiac antibody-mediated rejection. The diagnostic criteria for its morphologic and immunopathologic components are enumerated, illustrated, and described in detail. Numerous challenges and unresolved clinical, immunologic, and pathologic questions remain to which a Working Formulation may facilitate answers.

AIMS: Heterozygous mutations in the transcription factor Nkx2.5 indicate a genetic cause for congenital heart diseases (CHDs) in human beings. The present study aimed to assess the prevalence of NKX2.5 mutations in Italian patients with sporadic non-syndromic and syndromic CHD, as well as to appraise any genotype-phenotype correlations. METHODS: One hundred Italian patients affected with CHD (90 had sporadic non-syndromic CHD and 10 had syndromic CHD) were screened for NKX2.5 mutations. The coding region and flanking regions involved in gene splicing of the CSX/NKX2.5 gene were amplified from genomic DNA by PCR, and mutational analysis was performed using denaturing high performance liquid chromatography and DNA sequencing. RESULTS: One previously reported NKX2.5 mutation (c.73C>T, p.R25C) was identified in two of the 100 CHD patients (2%). We have detected the p.R25C alteration in a woman showing aneurysm of the membranous septum, aortic coarctation and bicuspid aortic valve, that was a different phenotype from those previously reported, and for the first time in a patient with syndromic CHD with Down's syndrome (posterior ventricular septal defect, atrial septal defect, left superior cava vein ' sinus, and patent ductus arteriosus). CONCLUSION: Our results confirm that NKX2.5 mutations are not a common cause of CHD; furthermore, the p.R25C variation may increase susceptibility to development of CHD in patients with and without chromosomal abnormalities.

Noncompaction cardiomyopathy is a rare disorder, often associated with cardiac and noncardiac malformations. Hirschsprung's disease, a well-known aganglionosis, is associated with congenital heart diseases and has been reported to be due to impairment migration and differentiation of neural crest cells. Here, we present an 8-month-old male infant who died for cardiogenic shock after surgical resection of the involved bowel segment. The child was affected by both noncompaction cardiomyopathy and Hirschsprung's disease, two entities which can share a common neural crest-derived etiology.

Surgical aortic specimens are usually examined in Pathology Departments as a result of treatment of aneurysms or dissections. A number of diseases, genetic syndromes (Marfan syndrome, Loeys–Dietz syndrome, etc.), and vasculopathic aging processes involved in vascular injury can cause both distinct and nonspecific histopathologic changes with degeneration of the media as a common denominator. Terminology for these changes has varied over time leading to confusion and inconsistencies. This consensus document has established a revised, unified nomenclature for the variety of noninflammatory degenerative aortic histopathologies seen in such specimens. Older terms such as cystic medial necrosis and medionecrosis are replaced by more technically accurate terms such as mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation and/or loss, and smooth muscle cell nuclei loss. A straightforward system of grading is presented to gauge the extent of medial degeneration and synoptic reporting tables are provided. Herein we present a standardized nomenclature that is accessible to general pathologists and useful for future publications describing these entities.

We analysed specificity and sensitivity of confocal laser microscopy (CLSM) on tissue sections for a diagnosis of amyloidosis, in an attempt to reduce technical errors and better standardise pathological diagnosis. We first set up a protocol for the use of CLSM on this type of specimen, using a group of 20 amyloid negative and 20 positive samples. Of all specimens, 2, 4 and 8-μm sections were cut. Sections were stained with Congo red (CR) and thioflavin-T (ThT) and observed by cross-polarised light microscopy (CR-PL), epifluorescence microscopy (CRF-epiFM and ThT-epiFM) and CLSM (CRF-CLSM and ThT-CLSM). To validate the method in a diagnostic setting, we examined tissue samples from 116 consecutive patients with clinical suspicion of amyloidosis, selected from the period 2005 to 2014 from the database of the Pathology Unit of the University of Padua. The results were compared with those of transmission electron microscopy (TEM), which we consider as reference. We found that with CRF-CLSM, the false negative rate was reduced from 17 to 5%, while the sensitivity of detection increased to 12%. The results were in complete agreement with those of TEM ThT-CLSM; both sensitivity and specificity were 100%. Finally, ThT-CLSM results did not vary with section thickness, and small amounts of amyloid could even be detected in 2-μm sections. In conclusion, we found ThT-CLSM to be more sensitive as a screening method for amyloidosis than CR and ThT epifluorescence optical imaging. The method was easier to standardise, provided images with better resolution and resulted in more consistent pathologist diagnoses.

Surgery for congenital valve anomalies in children is a challenging topic. We aim to assess early and late functional outcomes of CorMatrix scaffold after repair of aortic and pulmonary valves (PV) in congenital heart disease in a prospective nonrandomized clinical study on children with congenital aortic (Group 1) or PV (Group 2) disease. Primary endpoints were reoperation or reintervention on semilunar valves and echocardiographic evidence of regurgitation or stenosis greater than mild. Results of PV repair in tetralogy of Fallot were compared with a control group of patients who underwent PV repair with polytetrafluoroethylene. A total of 22 consecutive selected patients with complex congenital heart disease were included: PV repair in 18 and aortic valve repair in 4. At discharge bidimensional echocardiography, semilunar valve regurgitation was mild in 50% of all patients. At a median follow-up of 23 months (4.3-51.3), reoperation for aortic valve replacement was necessary in 2; right ventricular outflow tract obstruction occurred in 3, requiring interventional treatment in 2. Pulmonary regurgitation degree worsened in most patients of Group 2 at follow up. When comparing patients with tetralogy of Fallot in Group 2 with patients who underwent PV repair with polytetrafluoroethylene, there were no significant differences in PV function at follow up. We conclude that CorMatrix scaffold for semilunar valve reconstruction does not present with significant advantages to traditional materials at mid term follow up. In addition, when used for pulmonary valve reconstruction, CorMatrix seems to show gradual functional deterioration in the mid term.

Light chain deposition disease (LCDD) is a rare plasma cell dyscrasia consisting of nonamyloidotic deposition of misfolded immunoglobulin light chain (LC) in tissues and organs. Heart involvement is a rare and late event in the course of the disease.1 Therefore, such a nonfibrillar deposition of LC in the myocardium has so far been described only in few endomyocardial biopsies. Potentially lethal ventricular arrhythmias and a nondiagnostic echocardiogram are 2 clinical hallmarks of the disease.1,2 In addition, no other in vivo imaging of the condition is presently available. A 52-year-old man was admitted to the emergency department for syncope at rest. ECG showed a sinus rhythm with negative T waves in inferolateral leads alternating with ventricular bigeminism and episodes of torsades de pointes triggered by R-on-T phenomenon (Figure 1A). The previous history included serum IgGκ + κ monoclonal gammopathies and nephrotic syndrome. The bone marrow biopsy showed 60% clonal plasma cells, and the kidney biopsy examination by immunofluorescence and immunoelectron microscopy was consistent with LCDD. Light microscopic finding of kidney biopsy showed glomeruli with increased mesangial cellularity and nodular expansion of mesangial matrix; mesangial nodules were positive at periodic acid Schiff and trichrome stain (Figure 2A …

This is one of the most important chapters for cardiac transplant pathologists as it treats the main cardiac diseases encountered in explanted native hearts in both adult and pediatric patients: ischemic heart disease, myocardial disease, congenital heart defects.

Many different noxae can affect the cardiac allograft prior to transplantation in relation to donor type or mode of death, donor management in Intensive Care Unit, during graft procurement and surgical procedure, and immediately after transplantation due to recipient’s general condition. All these can injure the graft and cause lesions comprehensively known as perioperative myocardial damage to the graft. This chapter summarizes the main histopathological substrates related to perioperative injury, which can be encountered at endomyocardial biopsy evaluation up to 6 weeks after transplantation or at autopsy after early death.

Autopsy still represents the gold standard procedure to identify the causes of death after transplantation and remains a key investigation in the integration of medical knowledge in cardiac transplantation. In this chapter, we have highlighted the major roles played by this irreplaceable procedure and dissected the many aspects, which should be evaluated during autopsy to reach a correct diagnosis, a full clinicopathological correlation with deep discussion with the clinicians before signing out the final report to ensure that all clinical questions have been addressed during autopsy, its role in the clinical governance of transplant centers for quality control and transplant-related clinical audit, education and research. With the protocol we have given also some practical information for carrying it out correctly and not to miss the unique opportunity for collecting tissues for further studies and setting of bioarchives and biobanking. The assessment of the technical aspects related to the surgical procedure, the identifications of complications related to transplantation and to the immunosuppression and the comorbidities are some of the points which will be addressed in more details.

Hypoplastic left heart syndrome (HLHS) [12] represents a complex congenital defect which is characterized by different entities as

The pulmonary valve atresia/critical valve stenosis is a congenital heart defect which develops during the fetal life and is characterized by a wide spectrum of severity as result of the blood flow remodeling process of the right ventricle outflow. In the atretic valve there is absence of communication between the right ventricle outflow and the size of the pulmonary trunk and the right ventricle can vary considerably. Very often massive hypertrophy of the right parietal wall contribute substantially to the hypoplasia of the ventricular cavity. The tricuspid valve is also affected, been very often diminutive and dysplastic.Three types of pulmonary valve morphology can be identified: type a: pulmonary valve atresia with imperforate valve; type b: critical pulmonary valve stenosis with three dysplastic valve leaflets; type c: critical pulmonary valve stenosis with bicuspid or unicuspid valve.

Valve replacement in children with functionally univentricular hearts remains challenging. The absence of small prostheses, the lack of growth, and the need for anticoagulation limit these procedures. We describe a 1-year follow-up of an extracellular matrix scaffold tube used as systemic atrio-ventricular valve in an infant.