Myxomas Research Articles

Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma.

High morbidity and mortality of cancer, especially colorectal cancer (CRC), in diabetic patients have been reported. In this study, we investigated the relationship between the presence of diabetes mellitus (blood hemoglobin A1C was 6.5% or higher at the time of diagnosis of CRC) and the progression and liver metastasis of CRC. Histopathological findings in the primary lesions, which were preferential to diabetes-complicated CRC (DM-CRC) and the liver metastasis, were also investigated. Of the 473 CRC patients who underwent curative surgical resection, 148 (31%) had diabetes. In DM-CRC cases, the stage was more advanced, with more cases in stage IV or postoperative disease recurrence. Histopathological findings correlated with liver metastasis in DM-CRC, including budding grade, perineural invasion, and myxomatous tumor stroma, and all were highly correlated with the stage. Additionally, myxomatous stroma showed the strongest correlation with liver metastasis in multivariate analysis. Myxomatous stroma in stage III cases correlated with liver recurrence. The myxomatous stroma was abundant in biglycan protein and contained numerous CD90-positive mesenchymal stem cells (MSCs). In human colon cancer cell line HT29, biglycan expression was induced by high sugar concentration, fatty acids, and insulin, and its contact co-culture with MSCs resulted in enhanced stemness and epithelial-mesenchymal transition phenotype. Thus, DM-CRC has higher malignant phenotypes compared to non-DM-CRC, and the involvement of diabetes-induced biglycan may act as a pathogenic factor.

Beneficial Effects of Mineralocorticoid Receptor Antagonism on Myocardial Fibrosis in an Experimental Model of the Myxomatous Degeneration of the Mitral Valve.

Mitral valve prolapse (MVP) patients develop myocardial fibrosis that is not solely explained by volume overload, but the pathophysiology has not been defined. Mineralocorticoid receptor antagonists (MRAs) improve cardiac function by decreasing cardiac fibrosis in other heart diseases. We examined the role of MRA in myocardial fibrosis associated with myxomatous degeneration of the mitral valve. Myocardial fibrosis has been analyzed in a mouse model of mitral valve myxomatous degeneration generated by pharmacological treatment with Nordexfenfluramine (NDF) in the presence of the MRA spironolactone. In vitro, adult human cardiac fibroblasts were treated with NDF and spironolactone. In an experimental mouse, MRA treatment reduced interstitial/perivascular fibrosis and collagen type I deposition. MRA administration blunted NDF-induced cardiac expression of vimentin and the profibrotic molecules galectin-3/cardiotrophin-1. In parallel, MRA blocked the increase in cardiac non-fibrillar proteins such as fibronectin, aggrecan, decorin, lumican and syndecan-4. The following effects are blocked by MRA: in vitro, in adult human cardiac fibroblasts, NDF-treatment-induced myofibroblast activation, collagen type I and proteoglycans secretion. Our findings demonstrate, for the first time, the contribution of the mineralocorticoid receptor (MR) to the development of myocardial fibrosis associated with mitral valve myxomatous degeneration. MRA could be a therapeutic approach to reduce myocardial fibrosis associated with MVP.

A Case of Suspected Pericardial Effusion caused by Left Atrial Rupture due to Myxomatous Mitral Valve Degeneration

A Case of Suspected Pericardial Effusion caused by Left Atrial Rupture due to Myxomatous Mitral Valve Degeneration

Assessment of Respiratory Rate in Dogs during the Sleep with Mitral Valve Endocardiosis, Complicated by Congestive Heart Failure Syndrome: the Degree of Adherence for this Test by Animal Owners and its Impact on Patient Survival

Relevance: Congestive heart failure in dogs is an urgent problem for Doctor of Modern Veterinary cardiology. Endocardiosis, or myxomatous mitral valve degeneration, is the most common acquired heart disease of dogs that has a potential adverse outcome. Accurate and timely diagnosis for this cardiopathology in dogs, and also effective monitoring of the progression of congestive heart failure syndrome are the most important problems of veterinary medicine. Purpose of research: To study the commitment of owners whose dogs with mitral valve endocardiosis to assess the respiratory rate of their pets during sleep and its impact on the survival of sick animals. Materials and methods. A prospective study of the survival rate of 181 dogs with mitral valve endocardiosis, complicated by congestive heart failure syndrome. Results: It was found that the degree of owners' commitment to assess the respiratory rate during sleep has a significant impact on the survival of dogs with mitral valve endocardiosis. The median life expectancy of sick dogs whose owners had a high commitment to monitoring respiratory function was significantly high. The survival time of sick dogs whose owners showed high adherence to the test was on average 604.8±53.1 days (variation from 0 to 1378; median – 452 days). In sick animals whose owners showed low adherence to assess the respiratory rate, the life expectancy was significantly low and averaged 279.9±28.9 days (variation from 0 to 1156; median – 122 days). In the Mann-Whitney test, this difference was found to be significant (p

Perspectives on surgical treatment of mitral valve disease.

A sound knowledge of the functional anatomy of the mitral valve and the alterations caused by different diseases is indispensable for surgeons treating patients with mitral valve disease. Rheumatic mitral valve disease remains the most common heart valvular disorder in developing countries, whereas mitral regurgitation due myxomatous degeneration of the valve is the most common in developed countries. The mitral valve should be repaired whenever possible, as long as the outcome is predictably better than that of replacement. The intraoperative decision to repair or replace is not always simple and depends on the experience of the surgeon and the pathological changes that caused mitral valve dysfunction.

Atrial myxomas arise from multipotent cardiac stem cells.

AimsCardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumours are a valuable research model because of the rarity of cardiac tumours, their clinical presentation and uncertain origin. Here, we assessed whether multipotent cardiac stem/progenitor cells (CSCs) give rise to atrial myxoma tissue.Methods and resultsTwenty-three myxomas were collected and analysed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos/CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately ≤10% of the c-kitpos/CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing, and sphere forming while exhibiting an abortive cardiac differentiation potential. Myxoma-derived CSCs possess a mRNA and microRNA transcriptome overall similar to normal myocardium-derived c-kitpos/CD45neg/CD31negCSCs , yet showing a relatively small and relevant fraction of dysregulated mRNA/miRNAs (miR-126-3p and miR-335-5p, in particular). Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumours in xenograft’s in immunodeficient NOD/SCID mice.ConclusionMyxoma-derived c-kitpos/CD45neg/CD31neg CSCs fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg/CD31neg CSCs. Taken together the data presented here suggest that human myxomas could be the first-described CSC-related human heart disease.

MicroRNAs and Their Potential Role as Biomarkers in Canine COngestive Heart Failure

Myxomatous mitral valvular degeneration (MMVD) is the most common heart disease in dogs, accounting for more than 70% of canine heart disease cases. It primarily affects middle‐aged small dogs, though, any dog can develop MMVD. It can affect all heart valves but is usually detected in mitral valves. Degenerative processes cause mitral valves to thicken and retract, creating an unwanted hole which blood can flow through. Tearing of mitral valves can lead to blood overflow and later, CHF in the heart’s left‐side. Currently, there are no medications proven to prevent, slow, or reverse the development of MMVD. Because of limited knowledge on MMVD, heart murmurs and coughing are the earliest means of detection. A microRNA (miRNA) is a small non‐coding RNA molecule, about 22 nucleotides long. We would test miRNA‐21, miRNA‐29a‐3p, miRNA‐210, and miRNA‐133a. If said miRNA significantly upregulated in CHF‐positive dog plasma, then upregulation of those miRNA could indicate development of MMVD. Plasma would be collected from dogs at an animal shelter. Plasma RNA would be purified using QIAzol Lysis Reagent. RT‐PCR would be used to reverse transcribe RNA to cDNA. SYBR Green (fluorescent dye) would detect miRNA amplification. If we can determine which miRNAs have a significantly high concentration in CHF‐positive dog plasma, we would be able to detect MMVD in pre‐developmental stages. For example, if a dog’s blood screening results show abnormal upregulation of miRNA precursor to MMVD, inhibitors of said miRNA could administered as a preventative measure.

Excellent long-term results with minimally invasive edge-to-edge repair in myxomatous degenerative mitral valve regurgitation.

Previous series of minimally invasive mitral valve repairs showed excellent results at up to 10 years of follow-up. The goal of this study was to assess the long-term durability beyond 10 years of the edge-to-edge repair for myxomatous degeneration performed through a minimally invasive approach. Ninety-seven consecutive patients (mean age 35 ± 9 years; left ventricular ejection fraction 63 ± 6%) with severe myxomatous mitral regurgitation (MR) underwent mitral valve repair through a right minithoracotomy between 1999 and 2006. MR was due to lesions involving the posterior leaflet (7.2% of patients), anterior leaflet (12.4%) and both leaflets (80.4%). No hospital deaths occurred. At hospital discharge all patients had no or trivial MR. Follow-up was 100% complete (median 15.5 years; interquartile range 13.6-17.0, max 19.3 years). The 16-year overall survival rate was 95.9 ± 2.02% [95% confidence interval (CI) 89.39-98.43]. At 16 years, the cumulative incidence function of cardiac death, with non-cardiac death as a competing risk, was 3.1 ± 1.75 (95% CI 0.83-8.02). Only 3 patients (4.1%) had redo operations for recurrent severe MR. At 16 years, the cumulative incidence functions of reoperation for and recurrence of MR ≥3+, with death as a competing risk, were 3.1 ± 1.76% (95% CI 0.83-8.02) and 5.6 ± 2.47% (95% CI 2.06-11.83), respectively. No predictors of recurrence of MR ≥3+ were identified. At the last follow-up, moderate MR (2+/4+) was detected in 17 patients (17.5%); most of the patients were in New York Heart Association functional class I-II (97%) and in sinus rhythm (90%). Minimally invasive mitral valve edge-to-edge repair through a right minithoracotomy for myxomatous degeneration appears to be an effective and durable approach even in the long-term follow-up (up to 19 years).

Dental Pulp Stem Cells for Tissue Engineered Heart Valve

Myxomatous mitral valve degeneration is the most acquired heart disease in dogs. To reduce the clinical progression of mitral valve degeneration and achieve the hemodynamic outcomes, many medical or surgical treatments have been motivated. The objectives of this study is to investigate the suitability of puppy deciduous teeth stem cells as a cell source for tissue engineered heart valves in dog with degenerative valve disease. Puppy deciduous teeth stem cells (pDSCs) were seeded on the scaffolds which made from polylactic acid (PLA), polycaprolactone (PLC) and silicone. The mechanical properties of the tissue engineered heart valves leaflets were characterized by biaxial tensile tests. Results showed that, deciduous teeth stem cells capable of differentiating into a variety of cell types. However, the ability of puppy deciduous teeth stem cells to differentiate declined with increasing passage number which correspond to the number of protein surface marker detection have been shown to decrease substantially by the fifth passage. PLA scaffold is significantly higher tensile strength than other materials. However, silicone showed the highest flaccidity. The results from this study may provide high regenerative capability and the essential information for future directions of heart valve tissue engineering.

A single nucleotide deletion resulting in a frameshift in exon 4 of TAB2 is associated with a polyvalular syndrome

Polyvalvularmyxomatous degeneration is a rare clinical condition. A 51-year-old male patient presented at our centre with all four heart valves with myxomatous degeneration and severe mitral and aortic regurgitation due to leaflet prolapse. The patient referred five further family members with valvular heart disease at different stages of presentation. The aim of this study was to investigate the genetic basis of this familial polyvalvularmyxomatous degeneration which was associated with mild dysmorphic facial anomalies and short stature. A detailed family history was recorded. Nine members of the family, affected or not by valvular heart disease, were studied clinically, echocardiographically and by detailed genetic analyses. Six of the nine family members had echocardiographic features of different degrees of degenerative heart valve disease. In addition, the affected subjects shared similar mild dysmorphic facial anomalies and short stature. Exome sequencing identified a rare heterozygous single nucleotide deletion in the TAB2 gene in all affected family members, which was absent in the unaffected members. A variant in the TAB2 gene is proposed as the cause of syndromic congenital heart disease, displaying congenital myxomatous degenerative heart valve disease, mild dysmorphic fascial anomalies and short stature in this family.

Hemangiosarcoma associated with Chemodectoma in an Old Pit Bull Bitch

Background: The prevalence of neoplasms in domestic animals has been augmenting over the years. Hemangiosarcoma, which most frequently affects large breed dogs, is a neoplasm with high metastatic power and corresponds to 5% of malignant neoplasms. Chemodectoma, a neoplasm that can have malignant or benign behavior, is uncommon, corresponding to less than 8% of all cardiac tumors, and originates from cardiac chemoreceptor cells and involves mainly the aortic and carotid bodies. The aim of this study is to describe the case of an elderly Pit Bull dog with hepatic hemangiosarcoma and chemodectoma associated with four other different tumors: hemangioma, papilloma, mastocitoma and melanoma.Case: A 14-year-old female Pit Bull, castrated, was presented to Veterinary Clinic of the Federal University of Santa Catarina (UFSC), Curitibanos Campus, Brazil. The owner referred apathy, hyporexia, and increased abdominal volume for two weeks. Physical examination showed emaciation and abdominal effusion. Abdominocentesis was performed, three liters of serosanguineous fluid was drained and a sample was sent for analysis. Complementary tests were requested and showed mild hypoalbuminemia, normocytic normochromic anemia, and lymphopenia. The ultrasound examination revealed thickening of vessels and hepatomegaly, in addition to the presence of an oval structure containing hyperechogenic cavitations. Diagnostic exploratory laparotomy was indicated, but the owner refused. Drug therapy was prescribed in a palliative manner and, during the clinical follow-up period, two abdominocentesis procedures and one thoracentesis procedure were performed, both resulting in simple transudate. Finally, the patient developed severe apathy, edema in all limbs, and died at home. Necroscopic examination was done and revealed hemoperitoneum and hemothorax; several nodules with diverse characteristics in the integument were noted, which were classified by histopathological analysis as follicular cyst, papilloma, cavernous hemangioma, mastocytoma, and melanoma. The histological sections of the liver sample showed hemangiosarcoma and those of the urinary bladder showed hemangiosarcoma metastases. In the heart, a nodule was found at the base of the aorta, which was characterized as chemodectoma. Besides that, there was myxomatous mitral valve degeneration. The necropsy report indicated that the cause of death was hypovolemic shock associated with complications from multiple tumors, particularly hepatic hemangiosarcoma and chemodectoma.Discussion: Hemangiosarcoma is a malignant tumor with invasive behavior. The patient was an elderly Pit Bull dog, a breed not described as being predisposed to this type of tumor. Similarly to other reports in the literature, there was abdominal effusion with rapid and recurrent evolution, progressive weight loss, and metastases in the urinary bladder. It is believed that thoracic effusion, limb edema, and hepatic venous congestion were probably caused by chemodectoma owing to right-sided congestive heart failure. Although not related to the cause of death of this patient, the presence of tumors like papilloma, mastocytoma, melanoma, and hemangioma is noteworthy because the canine had a total of six different types of neoplasms, rarely reported in Pit Bull dogs. This work emphasizes the importance of necroscopic evaluation, which, in this case, was essential for the definitive diagnosis.

Deficiency of Circulating Monocytes Ameliorates the Progression of Myxomatous Valve Degeneration in Marfan Syndrome.

Myxomatous valve degeneration (MVD) involves the progressive thickening and degeneration of the heart valves, leading to valve prolapse, regurgitant blood flow, and impaired cardiac function. Leukocytes composed primarily of macrophages have recently been detected in myxomatous valves, but the timing of the presence and the contributions of these cells in MVD progression are not known. We examined MVD progression, macrophages, and the valve microenvironment in the context of Marfan syndrome (MFS) using mitral valves from MFS mice (Fbn1C1039G/+), gene-edited MFS pigs (FBN1Glu433AsnfsX98/+), and patients with MFS. Additional histological and transcriptomic evaluation was performed by using nonsyndromic human and canine myxomatous valves, respectively. Macrophage ontogeny was determined using MFS mice transplanted with mTomato+ bone marrow or MFS mice harboring RFP (red fluorescent protein)-tagged C-C chemokine receptor type 2 (CCR2) monocytes. Mice deficient in recruited macrophages (Fbn1C1039G/+;Ccr2RFP/RFP) were generated to determine the requirements of recruited macrophages to MVD progression. MFS mice recapitulated histopathological features of myxomatous valve disease by 2 months of age, including mitral valve thickening, increased leaflet cellularity, and extracellular matrix abnormalities characterized by proteoglycan accumulation and collagen fragmentation. Diseased mitral valves of MFS mice concurrently exhibited a marked increase of infiltrating (MHCII+, CCR2+) and resident macrophages (CD206+, CCR2-), along with increased chemokine activity and inflammatory extracellular matrix modification. Likewise, mitral valve specimens obtained from gene-edited MFS pigs and human patients with MFS exhibited increased monocytes and macrophages (CD14+, CD64+, CD68+, CD163+) detected by immunofluorescence. In addition, comparative transcriptomic evaluation of both genetic (MFS mice) and acquired forms of MVD (humans and dogs) unveiled a shared upregulated inflammatory response in diseased valves. Remarkably, the deficiency of monocytes was protective against MVD progression, resulting in a significant reduction of MHCII macrophages, minimal leaflet thickening, and preserved mitral valve integrity. All together, our results suggest sterile inflammation as a novel paradigm to disease progression, and we identify, for the first time, monocytes as a viable candidate for targeted therapy in MVD.

423 Effects of mitral valve repair on left ventricular remodeling and ventricular arrhythmia in mitral valve prolapse patients: five-year follow-up

Abstract Introduction There is limited data on the efficacy of surgical repair in reducing ventricular arrhythmia (VA) in mitral valve prolapse (MVP) patients. Improvement in malignant ventricular arrhythmias has been reported only in isolated cases after mitral valve surgery. Our aim was to evaluate the possible effects of mitral valve repair on left ventricular (LV) reverse remodeling and incidence of VA in MVP patients in mid-term follow-up. Methods 30 consecutive patients (mean age 53.1 ± 9.4, 47% male) undergoing mitral valve repair for severe mitral regurgitation (MR) due to mitral valve prolapse were enrolled in our observational, prospective, single-center study. Resected abnormal segments of the mitral leaflets were examined by experienced pathologists for signs of myxomatous degeneration. Transthoracic echocardiography extended with speckle-tracking echocardiography and 24-hour Holter monitoring were performed pre- and postoperatively annually. Atrial fibrillation, PVCs and nonsustained ventricular tachycardia (VT) runs were reviewed. Results During 144 person-years of follow-up no deaths, and 3 cases (10%) of recurrent moderate or severe (≥2) MR occurred. The total number of PVCs and non-sustained ventricular tachycardia runs dropped significantly in 1st (p=.04, Wilcoxon matched pairs test) and 2nd (p=.03), years of postoperative follow-up. Postoperative incidence of PVC and VT correlates strongly with postoperative end-diastolic LV diameter (EDD rs=.70; p=.005), moderate negatively with LV ejection fraction (EF rs=-.55; p=.01), but not postoperative MR (p>.05). EDD (58.8 ± 7.6 mm vs. 49.9 ± 5.6 mm; p=.00001) and EDV (156.6 ± 32.1 ml vs. 104.1 ± 22.8 ml; p=.00001) decreased in 1st year after repair with non-significant changes in EF (63.8 ± 12.8% vs. 59.6 ± 14.5%; p=.20), global systolic longitudinal strain –13.8 ± 2.5% vs. –14.6 ± 2.7%; p=.20) and SR (–0.93 ± 0.12 s-1 vs. –0.98 ± 0.13 s-1; p=.09) values. In univariate analysis, postoperative end-diastolic LV diameter (p=.001), low EF (p=.003), myxomatous degeneration (p=.008) were identified as risk factors of persistent PVCs/VT after surgery. Conclusions Mitral valve repair in MVP with severe mitral regurgitation is associated with reduction in ventricular arrhythmia, which strongly correlates with postoperative LV dimensions and function. Further investigation in larger cohorts to evaluate the association between degenerative mitral valve disease and ventricular arrhythmia is needed.

Myxomatous degeneration of the bicuspid aortic-valve

Bicuspid aortic-valve (BAV) is the most common congenital malformation. Complications include aortic stenosis and regurgitation, endocarditis, aortic dilatation and dissection. Although BAV is associated with early valve degeneration, its pathophysiology remains unknown. The objective of this study was to examine at clinical, histological and molecular levels, a cohort of BAV patients with pure aortic regurgitation (AR-BAV). From 2011 to 2018, patients with BAV were prospectively included. We performed histological and transcriptomic analysis of explanted BAV and compared differences between characteristics of prolapsed leaflet and non-prolapsed leaflet, using a normal tricuspid valve leaflet at reference. Aortic-valves from patients with long term left ventricular assist device (LVAD) were used as a model of acquired aortic regurgitation. A total of 350 patients with BAV were included. Among 316 patients (90%) with dysfunctional BAV, 66 (21%) presented severe AR-BAV. Mechanism of AR was prolapse in 37 patients (56%). Histologically, analysis of 2 explanted AR-BAV showed disorganization of extracellular matrix, loss of laminar structure and proteoglycans accumulation on prolapsed leaflet. Inversely, trilaminar structure of the non-prolapsed aortic leaflet was preserved. Transcriptomic analysis revealed upregulation of genes involved in extracellular matrix homeostasis and downregulation of endothelial cell markers on the prolapsed leaflet. The aortic-valve LVAD analysis found histological and molecular results similar to those described in BAV prolapsed leaflet and was associated with occurrence AR. AR-BAV is a mood of BAV dysfunction that occurs in young male subjects, as a consequence of myxomatous degeneration similar to that described in mitral valve prolapse. LVAD model suggests that altered hemodynamic environment could account for the acquired nature of valve degeneration.

479 When 2 rights make a wrong

Abstract Background The presence of an intra-cardiac mass is always a cause for concern, with regards to not only aetiology, but also treatment of complications. We describe a case series of 2 right sided cardiac myxomas, where the first case described an unusual location for tumour occurrence, while the second case provided insights into complications of a cardiac myxoma. Methods The first case involved a 70 year old asymptomatic lady who was referred for an additional heart sound. A transthoracic echocardiogram (TTE) showed a large, mobile 1.5 X 1.2 cm mass, attached to the atrial surface of septal tricuspid valve leaflet, prolapsing in and out of the right sided chambers. This was confirmed on transoesophageal echocardiogram (TEE). Cardiac MRI (magnetic resonance imaging) showed a similar mass attached to the septal tricuspid leaflet with features consistent with a myxoma. She was referred to cardiothoracic surgery, and 2 lobulated tumours arising the septal tricuspid valve and adjacent posterior leaflet were seen. The tumours were resected and a bio-prosthetic tricuspid valve replacement implanted. Histology of the tumours showed myxomatous degeneration of tricuspid valve, consistent with cardiac myxoma. The second case was a 56 year old lady who had dyspnoea, pedal oedema and an elevated jugular venous pulse on examination. A TTE done showed a large 7 X 4 cm mass extending from the right atrium (RA) into the right ventricle (RV). The left ventricular ejection fraction was 35%. Cardiac MRI confirmed the presence of a large mass in the right ventricle that exerted pressure effects on the ventricular septum and RV anterior free wall. Intra-operatively, a large RA mass attached by a stalk to the fossa ovalis was seen. The mass was excised and histology was consistent with cardiac myxoma. A repeat transthoracic echocardiogram done 2 weeks later showed normalisation of the LVEF. See images below for more information. Conclusion While myxomas are the most common benign cardiac tumours, they occur less commonly in the right atrium, and much less so on the tricuspid valve. Clinical manifestations range from being completely asymptomatic, as in the 1st case, to non-specific constitutional symptoms such as fever or general malaise, and to life-threatening complications. These include embolism to the pulmonary circulation, causing sudden death, or to the systemic circulation through an intra-cardiac shunt, causing strokes. This risk is increased if the tumour is large, polypoidal and friable. Large tumours can also cause obstructive symptoms and heart failure. Thus timely diagnosis with multi-modality imaging tools, and definitive treatment with complete resection of the tumour are essential. Continued monitoring for recurrences of the tumour, which can occur in 1-5% of all cases, should be performed as well. Abstract 479 Figure. Right sided cardiac masses

Myxomatous degeneration of the left atrioventricular valve in a true parrot (Amazona aestiva): a case report

Owning wild species as pets is becoming more and more common. Consequently, experience in caring for them has grown, resulting in the diagnosis of numerous diseases. Among these are cardiovascular disorders, especially in parrots. However, the lack of specificity or the absence of clinical signs of these diseases make it difficult to assess cardiovascular issues during the physical examination of birds. This leads to underdiagnosis of these conditions, with the majority being diagnosed post-mortem. This study reports the cardiovascular findings in post-mortem examinations of individuals of the species Amazona aestiva (true parrot) of Centro de Triagem de Animais Silvestres do Rio de Janeiro (CETAS-RJ) and is the first record of myxomatous degeneration of the left atrioventricular valve in this species.

P680 Aortic arch myxoma with multiple peripheral embolism.

Abstract We report an unusual localisation of myxoma, the most common primary cardiac neoplasm. A 58-year-old woman was admitted to surgery department with exacerbation of abdominal discomfort and symptoms of lower limb claudication.The abdominal CT showed embolism in the upper mesenteric artery arms with intestinal ischemia, in the minor renal arteries with kidney infarcts and in the minor arteries of lower extremities. She was urgently, succesfully operated and partial resection of the small intestine was performed. The chest angio-CT conducted three days after the operation revealed additional structure in the aortic arch. Local aortic arch dissection with a thrombus was initially suspected. Echocardiography showed homogenous tumor on the minor curvature of the aortic arch, with a base of 11 mm of width, reaching down with the blood stream towards the descending aorta. The aortic wall was linear, with no signs of dissection or atherosclerotic lesions, echogenicity indicated rather solid mass. The patient was operated cardiosurgically and tumor of a myxoma type was confirmed intraoperatively. Another, small tumor of the same type was found below isthmus, in a descending aorta. Partial resection of aortic arch, alloplasty of aortic arch with the use of a dacron prosthesis were performed. The tumor below the isthmus was removed, without resection of aortic wall, due to the high risk associated with the widening of the procedure. Multimodality imaging with the essential role of echocardiography is useful especially in differential diagnostics of the atypically localized tumors causing diffuse peripheral embolization. Abstract P680 Figure. Aortic arch myxoma tumor

P4483Transforming growth factor-beta and arrhythmias in mitral valve prolapse patients

Abstract Transforming growth factor-β (TGF-β) is a multifunctional cytokine with fibrogenic properties. Also increased TGF-β signaling contributes to the development of myxomatous changes of the mitral valve (MV). Recent data suggests that TGF-β may play a potentially important role in the heart arrhythmogenesis. Our aim was to evaluate the possible proarrhythmic effects of TGF-β in patients with mitral valve prolapse (MVP) and severe mitral regurgitation (MR) undergoing MV repair. Methods 30 consecutive patients (mean age 53.1±9.4, 47% male) undergoing MV repair for severe MR due to MVP were enrolled in our observational, prospective, single-center study. Immunohistochemical characterization of mitral valve sections was performed with TGF-β1 and TGF-β2 primary antibodies. The levels of TGF-β1 and TGF-β2 in serum were determined by enzyme-linked immunosorbent assay Human Platinum ELISA.Transthoracic echocardiography and 24-hour Holter monitoring were performed pre- and postoperatively annually. Atrial fibrillation, PVCs and nonsustained ventricular tachycardia (VT) runs were reviewed. Results Resected MV leaflets showed the increase ofTGF-β1 and TGF-β2 positive cell count (33% and 38%, respectively). High level of TGF-β1 (>14.75 ng/ml) and/or TGF-β2 (>2.0 ng/ml) was detected in majority (77%) of patients and associated with thickening of posterior leaflet (r=0.67; p=0.016), residual valve prolapse (r=0.68; p=0.007) and recurrent MR (r=0.56; p=0.01), pre- and postoperative left atrial (p<0.001) and end-systolic LV diameter (p<0.001), and negatively with LV ejection fraction (p<0.001). Atrial fibrillation was documented in 20% patients before repair. Postoperative AF occurred in 17% and associates with postoperative left atrial diameter (rs=0.60; p=0.008) and MR degree (rs=0.51; p=0.01). Total number of PVCs and non-sustained ventricular tachycardia runs dropped significantly in 1st (p=0.04, Wilcoxon matched pairs test) and 2nd (p=0.03), years of postoperative follow-up. Postoperative incidence of PVCs and VT associates strongly with postoperative end-diastolic LV diameter (rs=0.70; p=0.005), moderate negatively with LV ejection fraction (rs=−0.55; p=0.01). TGF-β2 (but not TGF-β1) serum level were associated with postoperative incidence of atrial fibrillation (p<0.001), but not PVCs or VT. In univariate analysis, postoperative left atrial diameter (p=0.001), residual MR (p=0.003), myxomatous degeneration (p=0.008) and the serum level of TGF-β2 (p=0.001) were identified as risk factors of persistent atrial fibrillation after surgery. Conclusions High level of TGF-β2 is associated with persistent atrial (but not ventricular) arrhythmias in MVP patients after mitral valve repair, possibly through 1) progression of valve myxomatous after reconstructive surgery (via recurrent MR and LA enlargement) and 2) previously shown alteration of the electrophysiological phenotype of cardiac myofibroblasts.

A RARE CASE OF CULTURE NEGATIVE WHIPPLE’S ENDOCARDITIS

SESSION TITLE: Cardiovascular Cases SESSION TYPE: Med Student/Res Case Report PRESENTED ON: 10/22/2019 3:45 PM - 4:45 PM INTRODUCTION: Whipple’s disease is a rare opportunistic infection (1 out of 1,000,000). The classical presentation of Whipple’s disease involves joint arthropathy (migratory oligoarticular or polyarticular) and digestive disorders (diarrhea and weight loss). Cardiovascular disease involvement is noted about one third of the time (pericarditis, congestive heart failure [CHF], or rarely culture-negative endocarditis). This case highlights the importance of a high clinical index of suspicion for Tropheryma whipplei culture-negative endocarditis, in the setting of rheumatologic disease and abrupt worsening of cardiac function, without overt gastrointestinal symptoms. CASE PRESENTATION: An 84-year-old man with past medical history of prostate cancer, polymyalgia rheumatica (PMR), cryptogenic stroke, and mild mitral valve prolapse of posterior mitral valve leaflet was admitted for severe mitral insufficiency with recent acute CHF symptoms. Documented diagnosis of PMR occurred 18 months prior to acute CHF symptoms, for which the patient was treated with continuous, extensive prednisone taper, starting at 15 mg daily. Clinical presentation of acute CHF and transthoracic echocardiography showing myxomatous degeneration of posterior mitral leaflet, partially flail, with severe mitral regurgitation, prompted evaluation by cardiothoracic surgery. Patient underwent mitral valve repair and pathology was suggestive of nonbacterial thrombotic endocarditis with vegetative studding of mitral valve anterior leaflet. Serum polymerase chain reaction for T. whipplei was negative and the patient was initially treated with intravenous vancomycin and cefepime. Antibiotic regimen transitioned to intravenous ceftriaxone 2gm daily and ampicillin-sulbactam 3 gm every 6 hours for 6 weeks for seronegative endocarditis of unknown etiology. Genome sequencing of valvular tissue detected T. whipplei deoxyribonucleic acid (DNA) with 16s ribosomal ribonucleic acid (rRNA) gene primer set and Periodic acid-Schiff (PAS) staining was positive. This case of Whipple’s endocarditis is currently being treated with trimethoprim-sulfamethoxazole for an anticipated 12 months. DISCUSSION: This case illustrates the importance of considering T. whipplei as a causal agent of culture-negative endocarditis, especially in the presence of rheumatologic disease and absence of overt gastrointestinal symptoms. Furthermore, in cases of recently diagnosed rheumatologic disease with iatrogenic immunosuppression, risk factors for T. whipplei exposure should be evaluated. The limitations of serum polymerase chain reaction assay as a diagnostic tool for T. whipplei further supports a high suspicion should be maintained in culture-negative endocarditis. CONCLUSIONS: A history of culture-negative endocarditis, in the presence of recently diagnosed and treated rheumatologic disease, without gastrointestinal symptoms should raise suspicion for Whipple's Endocarditis. Reference #1: Fenollar, Florence, et al. “Whipples Disease.” New England Journal of Medicine, vol. 356, no. 1, 2007, pp. 55–66., https://doi.org/10.1056/nejmra062477. Reference #2: Alozie, Anthony, et al. “Arthralgia and Blood Culture-Negative Endocarditis in Middle Age Men Suggest Tropheryma Whipplei Infection: Report of Two Cases and Review of the Literature.” BMC Infectious Diseases, vol. 15, no. 1, 2015, https://doi.org/10.1186/s12879-015-1078-6. Reference #3: Gabus, Vincent, et al. “Tropheryma Whipplei Tricuspid Endocarditis: a Case Report and Review of the Literature.” Journal of Medical Case Reports, vol. 4, no. 1, 2010, https://doi.org/10.1186/1752-1947-4-245. DISCLOSURES: No relevant relationships by SIJAN BASNET, source=Web Response no disclosure on file for Ronald Herb; No relevant relationships by Abigayle Sullivan, source=Web Response No relevant relationships by Emily Zagorski, source=Web Response

Stress-induced remodelling of the mitral valve: a model for leaflet thickening and superimposed tissue formation in mitral valve disease.

In mitral valve prolapse (MVP), leaflet thickening has recently been suggested to be due, in addition to a myxomatous degeneration, to the presence of a superimposed tissue (SIT), defined as an additional fibrous layer on top of the original leaflet. The mechanisms of SIT formation are currently unknown. We hypothesized that SIT formation would result from excessive leaflet stress and we used a unique ex vivo model to assess the correlation between leaflet remodelling and the type and location of mechanical stress and to elucidate the mechanisms underlying SIT formation. Human diseased mitral valves (MVs; n = 21) were histologically analysed for SIT formation and original leaflet thickening. The SIT comprised of various compositions of extracellular matrix and could reach more than 50% of total leaflet thickness. Original leaflet and SIT thickness did not show significant correlation (r = -0.27, P = 0.23), suggesting different regulatory mechanisms. To study the role of the mechanical environment on MV remodelling, mouse MV were cultured in their natural position in the heart and subjected to various haemodynamic conditions representing specific phases of the cardiac cycle and the MVP configuration. SIT formation was induced in the ex vivo model, mostly present on the atrial side, and clearly dependent on the duration, type, and extent of mechanical stress. Specific stainings and lineage tracing experiments showed that SIT comprises of macrophages and myofibroblasts and is associated with the activation of the transforming growth factor-beta and bone morphogenetic protein signalling pathways. Migration of valvular interstitial cells and macrophages through breakages of the endothelial cell lining contributed to SIT formation. Mechanical stresses induce specific cellular and molecular changes in the MV that result in SIT formation. These observations provide the first insights in the mechanism of SIT formation and represent an initial step to identify potential novel and early treatment for MVP.