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INTRODUCTION: Lesion Index (LSI) has been developed to predict lesion efficacy during radiofrequency (RF) catheter ablation. However, its value in predicting lesions size has still to be established. The aim of our study was to assess the lesions size reproducibility for prespecified values of LSI reached during RF delivery in an in vivo beating heart. METHODS: Ablation lesions were created with different values of LSI in seven domestic pigs by means of a contact force-sensing catheter (TactiCathTM , Abbott). Lesions were identified during RF delivery by means of a three-dimensional mapping system (EnSiteTM Precision, Abbott) and measured after heart explantation. Histology was carried out after gross examination on the first three lesions to confirm the accuracy of the macroscopic evaluation. RESULTS: A total of 64 myocardial lesions were created. Thirty-nine lesions were excluded from the analysis for the following reasons: histological confirmation of macroscopic lesion measurement (n = 3), transmurality (n = 24), unfavorable anatomic position (n = 10), not macroscopically identifiable (n = 2). In a final set of 25 nontransmural lesions, injury width and depth were, respectively, 4.6 ± 0.6 and 2.6 ± 0.8 mm for LSI = 4, 7.3 ± 0.8 and 4.7 ± 0.6 mm for LSI = 5, and 8.6 ± 1.2 and 7.2 ± 1.1 mm for LSI = 6. A strong linear correlation was observed between LSI and lesion width (r = .87, p < .00001) and depth (r = .89, p < .00001). Multiple linear regression analysis identified LSI as the only ablation parameter that significantly predicted lesion width (p < .001) and depth (p < .001). CONCLUSION: In our in vivo study, LSI proved highly predictive of lesion size and depth.
Subject(s)
Catheter Ablation , Animals , Catheter Ablation/adverse effects , Catheter Ablation/methods , Catheters , Heart , Humans , Reproducibility of Results , Sus scrofa , SwineABSTRACT
INTRODUCTION: Transcatheter mitral valve replacement (TMVR) is indicated in case of degenerated bioprosthesis in high-risk patients. However, durability of these valves still represents an important issue. METHODS: Early severe structural valve deterioration of a mitral porcine surgical bioprosthesis and of a subsequent bovine TMVR, both at 4 years follow-up, is here presented. RESULTS: Gross, histopathologic, and X-ray examination revealed massive calcification of both devices and fibrous tissue overgrowth involving the TMVR stent. CONCLUSIONS: Careful clinical evaluation and strict follow-up are mandatory to identify early signs of dysfunction and to intervene in a timely manner.
Subject(s)
Bioprosthesis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Animals , Cardiac Catheterization , Cattle , Humans , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Swine , Treatment OutcomeABSTRACT
Neurological manifestations are common in COVID-19, the disease caused by SARS-CoV-2. Despite reports of SARS-CoV-2 detection in the brain and cerebrospinal fluid of COVID-19 patients, it is still unclear whether the virus can infect the central nervous system, and which neuropathological alterations can be ascribed to viral tropism, rather than immune-mediated mechanisms. Here, we assess neuropathological alterations in 24 COVID-19 patients and 18 matched controls who died due to pneumonia/respiratory failure. Aside from a wide spectrum of neuropathological alterations, SARS-CoV-2-immunoreactive neurons were detected in the dorsal medulla and in the substantia nigra of five COVID-19 subjects. Viral RNA was also detected by real-time RT-PCR. Quantification of reactive microglia revealed an anatomically segregated pattern of inflammation within affected brainstem regions, and was higher when compared to controls. While the results of this study support the neuroinvasive potential of SARS-CoV-2 and characterize the role of brainstem inflammation in COVID-19, its potential implications for neurodegeneration, especially in Parkinson's disease, require further investigations.
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AIMS: Myocardial longitudinal strain (LS) by two-dimensional (2D) speckle-tracking echocardiography has a diagnostic and prognostic role in cardiac amyloidosis (CA). Typically, the apical segments of the left ventricle (LV) are less affected by LS abnormalities, a finding called relative apical sparing (RELAPS). Whether a variable burden of CA might explain the RELAPS remains unknown.We aimed to evaluate the extent, distribution, and deposition pattern of amyloid in autopsy hearts of CA patients and to correlate the histopathology findings with 2D echocardiography. METHODS AND RESULTS: This is a retrospective study of whole heart specimens of CA patients who died and underwent autopsy and 2D echocardiography. Amyloid burden quantification was assessed by histomorphometry in each segment at different LV levels. The LS analysis results were compared with the amyloid burden and the base-to-apex distribution.Histopathology investigation of 27 hearts with CA [immunoglobulin light chains (AL) 17 cases and transthyretin (ATTR) 10 cases] demonstrated an amyloid base-to-apex gradient. In 11 CA patients with 2D echocardiography, analysis of LS and histological amyloid burden allowed to identify different patterns: RELAPS (8 cases, 73%), with (2) or without (6) amyloid gradient, normal or mildly reduced LS with diffuse low amyloid (2, 18%), and severely reduced LS with diffuse high amyloid (1, 9%). CONCLUSION: The typical RELAPS pattern at echocardiography is not always explained by a base-to-apex gradient of amyloid burden at histopathology, suggesting that RELAPS might be an epiphenomenon of complex interactions among amyloid infiltration, myocardial structure, and adaptation.
Subject(s)
Amyloidosis , Cardiomyopathies , Humans , Retrospective Studies , Cardiomyopathies/pathology , Amyloidosis/diagnostic imaging , Amyloidosis/pathology , Myocardium/pathology , EchocardiographyABSTRACT
BACKGROUND: Chest pain is experienced by patients with cardiac amyloidosis (CA), but a systematic investigation of its frequency, underlying etiologies and clinical significance is lacking. METHODS: Clinical, echocardiographic, laboratory characteristics, available coronary arteries imaging and endomyocardial biopsy (EMB) findings of 174 patients with CA (n = 104 with transthyretin, ATTR; n = 70 with light chains, AL) were analyzed. RESULTS: Chest pain was reported in 66 (38%) CA patients. Compared to those without, patients with chest pain had more frequently a history of coronary artery disease (CAD) (27% vs 15%, p = 0.048) and heart failure (HF) symptoms (62% vs 43%, p = 0.015), higher high sensitivity troponin I (hs-cTnI, 101 vs 65 ng/L, p = 0.032) and higher brain natriuretic peptide (597 vs 407 ng/L, p = 0.024). Among CA patients with chest pain undergoing coronary arteries imaging (n = 37), obstructive CAD was detected in 14 (38%), 13 of whom with ATTR-CA. Of these 37 patients, EMB was available in 10 and vascular/perivascular amyloid deposition was detected in 4/5 (80%) of AL-CA patients and 1/5 ATTR-CA. Among patients with suspected acute coronary syndrome (n = 22), obstructive CAD was detected in 9/17 (53%) ATTR-CA and 0/5 AL-CA; hs-cTnI levels were similar between those with and without obstructive CAD. During a follow-up of 17 (8-34) months, chest pain was a significant predictor of HF hospitalization (HR1.86, 95% CI 1.02-3.39, p = 0.042), even after adjustment for CA subtype and CAD. CONCLUSION: Chest pain is a common symptom in patients with CA, reflects a more advanced cardiac impairment and predicts future HF hospitalization. The etiology of chest pain seems to differ, with obstructive CAD more frequent in ATTR-CA whilst amyloid vascular/perivascular involvement more common in AL-CA.
Subject(s)
Amyloidosis , Coronary Artery Disease , Heart Diseases , Immunoglobulin Light-chain Amyloidosis , Humans , Prognosis , Amyloidosis/complications , Amyloidosis/diagnosis , Amyloidosis/epidemiology , Chest Pain/diagnosis , Chest Pain/epidemiology , Chest Pain/etiology , Coronary Artery Disease/diagnosisABSTRACT
AIMS: Bioprosthetic heart valves (BHVs), made from glutaraldehyde-fixed heterograft materials, are subject to more rapid structural valve degeneration (SVD) in paediatric and young adult patients. Differences in blood biochemistries and propensity for disease accelerate SVD in these patients, which results in multiple re-operations with compounding risks. The goal of this study is to investigate the mechanisms of BHV biomaterial degeneration and present models for studying SVD in young patients and juvenile animal models. METHODS AND RESULTS: We studied SVD in clinical BHV explants from paediatric and young adult patients, juvenile sheep implantation model, rat subcutaneous implants, and an ex vivo serum incubation model. BHV biomaterials were analysed for calcification, collagen microstructure (alignment and crimp), and crosslinking density. Serum markers of calcification and tissue crosslinking were compared between young and adult subjects. We demonstrated that immature subjects were more susceptible to calcification, microstructural changes, and advanced glycation end products formation. In vivo and ex vivo studies comparing immature and mature subjects mirrored SVD in clinical observations. The interaction between host serum and BHV biomaterials leads to significant structural and biochemical changes which impact their functions. CONCLUSIONS: There is an increased risk for accelerated SVD in younger subjects, both experimental animals and patients. Increased calcification, altered collagen microstructure with loss of alignment and increased crimp periods, and increased crosslinking are three main characteristics in BHV explants from young subjects leading to SVD. Together, our studies establish a basis for assessing the increased susceptibility of BHV biomaterials to accelerated SVD in young patients.
Subject(s)
Bioprosthesis , Calcinosis , Heart Valve Prosthesis , Animals , Rats , Sheep , Heart Valves , Biocompatible Materials , CollagenABSTRACT
Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by progressive loss of the ventricular myocardium causing life-threatening ventricular arrhythmias, syncope and sudden cardiac death in young and athletes. About 40% of AC cases carry one or more mutations in genes encoding for desmosomal proteins, including Desmoplakin (Dsp). We present here the first stable Dsp knock-out (KO) zebrafish line able to model cardiac alterations and cell signalling dysregulation, characteristic of the AC disease, on which environmental factors and candidate drugs can be tested. Our stable Dsp knock-out (KO) zebrafish line was characterized by cardiac alterations, oedema and bradycardia at larval stages. Histological analysis of mutated adult hearts showed reduced contractile structures and abnormal shape of the ventricle, with thinning of the myocardial layer, vessels dilation and presence of adipocytes within the myocardium. Moreover, TEM analysis revealed "pale", disorganized and delocalized desmosomes. Intensive physical training protocol caused a global worsening of the cardiac phenotype, accelerating the progression of the disease. Of note, we detected a decrease of Wnt/ß-catenin signalling, recently associated with AC pathogenesis, as well as Hippo/YAP-TAZ and TGF-ß pathway dysregulation. Pharmacological treatment of mutated larvae with SB216763, a Wnt/ß-catenin agonist, rescued pathway expression and cardiac abnormalities, stabilizing the heart rhythm. Overall, our Dsp KO zebrafish line recapitulates many AC features observed in human patients, pointing at zebrafish as a suitable system for in vivo analysis of environmental modulators, such as the physical exercise, and the screening of pathway-targeted drugs, especially related to the Wnt/ß-catenin signalling cascade.
ABSTRACT
The Sorin Pericarbon Freedom (SPF) valve is a stentless bioprosthesis made from bovine pericardium, with a peculiar design aimed at preventing the mechanical failures observed with old models of stented pericardial bioprostheses. Herein, the case is described of a patient who presented with severe regurgitation of a SPF six years after aortic valve replacement, caused by commissural dehiscence. Both, microradiographic and histologic investigations, revealed mild calcific deposits and massive lipid infiltration, thus confirming that a patient-related mechanism such as 'atheromasia' can account for structural valve deterioration also in recipients of pericardial bioprostheses.
Subject(s)
Aortic Valve Insufficiency/surgery , Calcinosis/etiology , Equipment Failure Analysis , Heart Valve Prosthesis/adverse effects , Lipid Metabolism Disorders/etiology , Aged, 80 and over , Animals , Bioprosthesis/adverse effects , Cattle , Female , Humans , Pericardium/transplantationABSTRACT
BACKGROUND AND AIM OF THE STUDY: The study aim was to investigate leaflet escape in the TRI-Tech mechanical valve, as reported in three patients. METHODS: Among the three patients, one patient with a mitral prosthesis from which leaflet escape occurred underwent a successful reoperation. However, two patients with an aortic prosthesis from which leaflet escape occurred died suddenly. In addition, 150 unimplanted TRI-Tech valve prostheses were evaluated. RESULTS: Tab fracture was observed in all of the escaped leaflets, with a height asymmetry of 0.33 mm in the mitral valve, and 0.55 and 0.41 mm, respectively, in the two aortic valves. Height tab asymmetry was present in all unimplanted valves: this was <0.20 mm in 90% of valves, and >0.20 mm in 10% (in one valve the asymmetry was >0.35 mm). Height asymmetry was greatest in valves sized 21 to 25 mm. A review of data provided by the TRI-Tech quality control unit failed to demonstrate any reference to checking for tab symmetry. CONCLUSION: Significant tab malalignment was observed in the TRI-Tech valves in which tab fracture and leaflet escape had occurred. Tab asymmetry was also present in all unimplanted valves; this was >0.20 mm in 10% of units, and in one case was as high as in valves that had undergone leaflet escape. As tolerance for tab asymmetry is unknown and the risk of rupture is unpredictable, an interruption of the implant program with prophylactic replacement of the implanted TRI-Tech valves must be considered judicious.
Subject(s)
Aortic Valve , Equipment Failure Analysis , Heart Valve Prosthesis/adverse effects , Mitral Valve , Prosthesis Failure , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
A unique specimen of argyria is preserved in the Morgagni Museum of Pathological Anatomy at the University of Padua (Italy). It is a stuffed head belonging to a man who decided to cure his syphilis by himself with the so-called infernal stone (silver nitrate) every day for years, thus developing argyria in the second half of the nineteenth century. Paleopathological and historical studies were performed on the specimen to confirm the diagnosis of argyria. Furthermore, a morphological investigation of the specimen was conducted with histological and ultrastructural investigations, including environmental scanning electron microscopy and electron dispersive x-ray spectroscopy, recording high presence of silver in the dermis and epidermis and also other chemical elements correlated to the "infernal stone." A comparison with actual cases may also lead to a common feature: a potential dependence on the perceived benefits brought by silver compound that may sustain a further prolonged intake.
Subject(s)
Argyria , Argyria/diagnosis , Argyria/pathology , Humans , Italy , Male , Microscopy, Electron, Scanning , Museums , Silver NitrateABSTRACT
Background: The major limitation to the Ross operation is a progressive autograft dilation, possibly leading to reoperations. A murine model was created to evaluate pulmonary artery graft (PAG) adaptation to pressure overload. Methods: Lewis rats (n = 17) underwent heterotopic surgical implantation of a PAG, harvested from syngeneic animals (n = 17). A group of sham animals (n = 7) was used as a control. Seriated ultrasound studies of the PAG were performed. Animals were sacrificed at 1 week (n = 5) or 2 months (n = 15) and the PAG underwent mechanical and histopathological analyses. Results: Echography showed an initial increase in diameter (p < 0.001) and a decrease in peak systolic velocity (PSV). Subsequently, despite no change in diameter, an increase in PSV was observed (p < 0.01). After 1 week, the stiffness of the PAG and the aorta were similar, while at 2 months, the PAG appeared more rigid (p < 0.05). PAG's histological analysis at 2 months revealed intimal hyperplasia development. The tunica media showed focal thinning of the elastic lamellae and normally distributed smooth muscle cells. Conclusions: We demonstrated a stiffening of the PAG wall after its implantation in systemic position; the development of intimal hyperplasia and the thinning of the elastic lamellae could be the possible underlying mechanism.
ABSTRACT
AIM: This study used morphometric analyses to compare two methods for the intra-oral harvesting of particulate bone: Mectron Piezosurgery® and the Meta Micross®. MATERIALS AND METHODS: Twenty patients requiring bilateral germectomy of the lower third molars for orthodontic reasons were selected and a sample was harvested from each patient from a standardised donor site (the cortical bone in the area of the retromolar triangle). Ten samples were obtained for each method. The particulate collected were subjected to a histological examination and the samples were analysed considering the following parameters: the mean surface area of fragments, the mean surface area considered vital and the mean surface area considered non-vital, the mean percentage of area considered vital and the mean percentage of area considered non-vital, the mean number of normal osteocytes and the mean number of osteocytes with morphological changes identified per unit area (600,000 µm(2)). The results were analysed, calculating the mean and the corresponding standard deviations, and testing their significance using Student's t-test, and plotted in graphs. RESULTS: Mectron Piezosurgery® produced significantly larger particles (P<0.05) than the Meta Micross®, with a larger mean surface area considered vital and a significantly larger (P<0.05) surface area considered non-vital. Mectron Piezosurgery® also produced a smaller mean percentage of area considered vital (64.83%) and a larger mean percentage of area considered non-vital (35.17%) by comparison with the Meta Micross® (75.34% and 24.66%, respectively). The data also showed that the two methods produce a similar quantity of empty lacunae, and that the Mectron Piezosurgery® produces a larger quantity of osteocytes. CONCLUSIONS: The analyses conducted demonstrated that the particulate collected with the Meta Micross® had a smaller mean surface area of the fragments and a smaller surface area of bone considered non-vital than in the particulate collected using Mectron Piezosurgery®.
Subject(s)
Mandible/surgery , Osteotomy/methods , Tissue and Organ Harvesting/methods , Cell Count , Cell Survival , Coloring Agents , Humans , Mandible/pathology , Molar, Third/surgery , Osteocytes/pathology , Osteotomy/instrumentation , Tooth Extraction/methods , Tooth Germ/surgery , VibrationABSTRACT
The aorta is not a rigid tube, it is an "organ" with lamellar units, consisting of elastic fibers, extracellular matrix and smooth muscle cells in between as parenchyma. Several diseases may occur in the natural history of the aorta, requiring replacement of both semilunar cusps and ascending aorta. They may be congenital defects, such as bicuspid aortic valve and isthmal coarctation with aortopathy; genetically determined, such as Marfan and William syndromes; degenerative diseases, such as atherosclerosis and medial necrosis with aortic dilatation, valve incompetence and dissecting aneurysm; inflammatory diseases such as Takayasu arteritis, syphilis, giant cell and IgM4 aortitis; neoplasms; and trauma. Aortic homografts from cadavers, including both the sinus portion with semilunar cusps and the tubular portion, are surgically employed to replace a native sick ascending aorta. However, the antigenicity of allograft cells, in the lamellar units and interstitial cells in the cusps, is maintained. Thus, an immune reaction may occur, limiting durability. After proper decellularization and 6 months' implantation in sheep, endogenous cell repopulation was shown to occur in both the valve and aortic wall, including the endothelium, without evidence of inflammation and structural deterioration/calcification in the mid-term. The allograft was transformed into an autograft.
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BACKGROUND: Limited mid-term durability of 12A/LX Mitroflow bioprosthesis has been reported. Aim of the study was to ascertain the pathologic substrates and possible mechanisms of structural valve deterioration in explants from animals and humans. METHODS: Nine aortic 12A/LX Mitroflow bioprostheses preserved in hypotonic solution and three aortic 12A/LX bioprostheses, preserved in isotonic solution, were explanted from juvenile sheep, mean time from implant 95.66 ± 36.04 days and 132.33 ± 28.88 days from implant respectively. One stented unimplanted 12A/LX Mitroflow preserved in isotonic colution before glutaraldeyde fixation served as control. Ten aortic 12A/LX Mitroflow bioprostheses were explanted from humans because of severe dysfunction: five children, (3 females and 2 males, mean age 14.19 ± 4.77 years, range 11-21), 26 ± 8.24 months from implant and 5 adults (4 females and 1 male, mean age 57.4 ± 19.85 years, range 31-72), 64.4 ± 26.94 months from implant. X-ray, histology, and transmission electron microscopy were carried out as well as spectroscopy for calcium (Ca++) and phosphorus (P) content in human explants. RESULTS: Explants, from both animals and humans, showed cusp folding and stiffness, with coarse calcific deposits at gross examination and X-ray. Severe collagen denaturation, plasma insudation and massive calcification, involving both collagen and cell debris, were observed microscopically. Mean Ca++ content of 183.27 ± 62.48 and P content of 94.35 ±33.76 mg/g dry weight was found in children and Ca++ content of 205.49 ± 2.23 and P content of 99.75 ± 0.11 mg/g dry weight in adults. Obstructive fibrous tissue overgrowth was detected in 6 human cases. CONCLUSIONS: Collagen denaturation was observed in pericardial Mitroflow 12A/LX bioprosthesis with premature structural valve deterioration. Optimal collagen fixation and preservation as well as phospholipids reduction by removing cell debris, as employed in the novel CROWN PRT Mitroflow bioprosthesis, are expected to solve the flaw and achieve long-term durability.
Subject(s)
Bioprosthesis , Heart Valve Prosthesis , Adolescent , Animals , Bioprosthesis/adverse effects , Child , Collagen , Female , Heart Valve Prosthesis/adverse effects , Humans , Male , Prosthesis Failure , Sheep , Young AdultABSTRACT
Perceval S is a self-expandable, stent-mounted bioprosthetic valve (BPV), with glutaraldehyde treated bovine pericardium, processed with homocysteic acid as an anti-calcification treatment. The stent is crimpable but the valve insertion is done surgically via a shorter procedure which does not require sutures. OBJECTIVES: MATERIAL AND METHODS: RESULTS: CONCLUSIONS: Collapsing and ballooning do not alter cusp collagen periodicity. Structural valve deterioration with stenosis, due to dystrophic calcification and fibrous tissue overgrowth, seldom occurred in the mid-term. Glutaraldehyde fixed pericardium has the potential to undergo structural valve deterioration with time, similar to well-known BPV failure. This supports the recommendation to pursue improvement of tissue valve treatment with enhanced durability.
Subject(s)
Bioprosthesis , Calcinosis , Heart Valve Prosthesis , Animals , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Bioprosthesis/adverse effects , Calcinosis/surgery , Cattle , Collagen , Heart Valve Prosthesis/adverse effects , Humans , Pericardium/surgery , Prosthesis Design , Prosthesis FailureABSTRACT
The histological diagnosis of pleural epithelioid mesothelioma can be difficult in the case of rare variants or in the definition of neoplasm origin in patients with previous or concomitant tumours. Currently, several immunohistochemical reactions are available in the surgical pathologist's armamentarium that allow us to obtain a more sensitive and specific diagnosis of malignant pleural mesothelioma. However, in some cases, the final interpretation remains inconclusive. Historically, ultrastructural examination has represented a useful tool for the definition of the mesothelial nature of neoplastic cells due to their peculiar morphological characteristics. The recent international guidelines for pathological diagnosis of pleural mesothelioma suggest the use of electron microscopy when the immunohistochemical reactions are equivocal or when further support of a diagnosis of mesothelioma is needed. This paper presents three cases of pleural epithelioid mesothelioma whose diagnoses were finally supported by ultrastructural examination.
ABSTRACT
BACKGROUND: Aortic stentless bioprosthetic valve (SLBPV), either porcine or pericardial, minimizes transvalvular gradient and favors regression of left ventricular hypertrophy. The drawback consists of longer time for suturing. While structural valve deterioration (SVD) in stented porcine and pericardial BPVs has been extensively investigated, less information is available on SLBPVs. MATERIAL AND METHODS: We studied 82 SLBPVs explants, either porcine (Toronto SPV, [St. Jude Medical, MN, USA], CryolifeO'Brien Model 300 and CryoLife-O'Brien [Cryolife International, GA, USA], BioCor PVS [St. Jude Medical, MN, USA] Prima and Prima Plus [Edwards Lifesciences Corp. One Edwards Way, CA, formerly Baxter Inc, CA, USA]) or pericardial ([Pericarbon Freedom and Freedom Solo [Sorin-Biomedica, S.p.A., Saluggia, Italy]). RESULTS: By excluding cases with leak and endocarditis, we focused the investigation on 46 SLBPVs, which failed because of SVD. Gender was male in 29 (63%). Mean age of patients at time of implant was 59.8 years. Postoperative time of SVD was 115.0 months for porcine and 79.0 months for pericardial SLBPVs. Dysfunction requiring reoperation was mainly incompetence for porcine and stenosis for pericardial SLBPVs. Even pinpoint mineralization at the commissures resulted in sudden cusp tearing and incompetence. Cuspal atheromasia accounted for cusp tearing even in the absence of calcification. Mineralization showed progression with time in pericardial but not in porcine SLBPVs. CONCLUSIONS: Tissue mineralization remains the nightmare also of SLBPVs, with the peculiar features of pinpoint calcific deposits at commissures, tearing and abrupt incompetence in porcine SLBPVs and of massive cuspal mineralization and stenosis in pericardial SLBPVs.
Subject(s)
Aortic Valve Stenosis/pathology , Aortic Valve/pathology , Aortic Valve/surgery , Bioprosthesis , Calcinosis/pathology , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis , Pericardium/transplantation , Prosthesis Failure , Aged , Animals , Aortic Valve Stenosis/etiology , Aortic Valve Stenosis/surgery , Calcinosis/etiology , Calcinosis/surgery , Device Removal , Female , Heart Valve Prosthesis Implantation/adverse effects , Heterografts , Humans , Male , Middle Aged , Pericardium/pathology , Prosthesis Design , Retrospective Studies , Sus scrofa , Time FactorsABSTRACT
BACKGROUND: Arrhythmogenic cardiomyopathy (AC) is a myocardial disease due to desmosomal mutations whose pathogenesis is incompletely understood. OBJECTIVE: The purpose of this study was to identify molecular pathways underlying early AC by gene expression profiling in both humans and animal models. METHODS: RNA sequencing for differentially expressed genes (DEGs) was performed on the myocardium of transgenic mice overexpressing the Desmoglein2-N271S mutation before phenotype onset. Zebrafish signaling reporters were used for in vivo validation. Whole exome sequencing was undertaken in 10 genotype-negative AC patients and subsequent direct sequencing in 140 AC index cases. RESULTS: Among 29 DEGs identified at early disease stages, Lgals3/GAL3 (lectin, galactoside-binding, soluble, 3) showed reduced cardiac expression in transgenic mice and in 3 AC patients who suffered sudden cardiac death without overt structural remodeling. Four rare missense variants of LGALS3 were identified in 5 human AC probands. Pharmacologic inhibition of Lgals3 in zebrafish reduced Wnt and transforming growth factor-ß signaling, increased Hippo/YAP-TAZ signaling, and induced alterations in desmoplakin membrane localization, desmosome integrity and stability. Increased LGALS3 plasma expression in genotype-positive AC patients and CD98 activation supported the galectin-3 (GAL3) release by circulating macrophages pointing toward the stabilization of desmosomal assembly at the injured regions. CONCLUSION: GAL3 plays a crucial role in early AC onset through regulation of Wnt/ß-catenin signaling and intercellular adhesion.
Subject(s)
Arrhythmogenic Right Ventricular Dysplasia/genetics , DNA/genetics , Galectin 3/genetics , Mutation , Animals , Arrhythmogenic Right Ventricular Dysplasia/metabolism , DNA Mutational Analysis , Disease Models, Animal , Galectin 3/metabolism , Mice , Mice, Transgenic , PhenotypeABSTRACT
Glutaraldehyde-treated, surgical bioprosthetic heart valves undergo structural degeneration within 10-15 years of implantation. Analogous preliminary results were disclosed for percutaneous heart valves (PHVs) realized with similarly-treated tissues. To improve long-term performance, decellularised scaffolds can be proposed as alternative fabricating biomaterials. The aim of this study was to evaluate whether bovine and porcine decellularised pericardia could be utilised to manufacture bioengineered percutaneous heart valves (bioPHVs) with adequate hydrodynamic performance and leaflet resistance to crimping damage. BioPHVs were fabricated by mounting acellular pericardia onto commercial stents. Independently from the pericardial species used for valve fabrication, bioPHVs satisfied the minimum hydrodynamic performance criteria set by ISO 5840-3 standards and were able to withstand a large spectrum of cardiac output conditions, also during extreme backpressure, without severe regurgitation, especially in the case of the porcine group. No macroscopic or microscopic leaflet damage was detected following bioPHV crimping. Bovine and porcine decellularized pericardia are both suitable alternatives to glutaraldehyde-treated tissues. Between the two types of pericardial species tested, the porcine tissue scaffold might be preferable to fabricate advanced PHV replacements for long-term performance. CONDENSED ABSTRACT: Current percutaneous heart valve replacements are formulated with glutaraldehyde-treated animal tissues, prone to structural degeneration. In order to improve long-term performance, bovine and porcine decellularised pericardia were utilised to manufacture bioengineered replacements, which demonstrated adequate hydrodynamic behaviour and resistance to crimping without leaflet architectural alteration.
Subject(s)
Bioprosthesis , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Animals , Cattle , Heart Valves , Materials Testing , SwineABSTRACT
Acute aortic root thrombosis extended to coronary ostia is a rare but potentially life-threatening complication of aortic valve replacement with bioprosthetic substitutes. We aimed to present the case of a 72-year-old woman with symptomatic rheumatic valve disease and associated atrial fibrillation who underwent conventional mitroaortic valve replacement with two stented bioprostheses (pericardial and porcine, respectively). Eight days after surgery, she had cardiac arrest due to ventricular fibrillation, requiring immediate cardiopulmonary resuscitation. Left ventricle akinesia by echocardiography and troponin levels up to 35,000â¯ng/L pointed to coronary ischemia. Emergent coronary angiography showed a subocclusion of the left main trunk, with the suspicion of aortic root thrombosis. The patient was immediately reoperated, fresh thrombi were removed from the aortic root, and the aortic Magna Ease 21-mm bioprosthesis was replaced with a stentless Solo Smart 21-mm bioprosthesis. The patient died of septic complications.