In Vitro and In Vivo Evaluation of Lyophilized Bioprosthetic Valve

Freeze-drying of biological tissues allows for dry storage and gamma ray sterilization, which may improve their use as a medical prosthesis. The objective of this study was to evaluate the rehydration characteristics and hydrodynamic performance of prosthetic valves before and after lyophilization. Two size 23 bovine pericardium aortic valve prostheses from different manufacturers were evaluated in a Shelhigh (Union, NJ, USA) pulse duplicator (80 ppm, 5 L/min) before and after lyophilization. Flow and transvalvular pressure gradient were registered in vitro and in vivo, and images of opening and closing of the prosthesis were obtained in the pulse duplicator in a digital camera. Rehydration was evaluated by comparison of dry valve weight with valve weight after 15 min, and 1, 24, 48, and 72 h in saline solution, inside the pulse duplicator. In vivo performance was assessed by surgical implantation in Santa Ines young male sheep in the pulmonary position after 30 min rehydration with 0.9% saline. Transvalvular pressure gradient and flow measurements were obtained immediately after implantation and 3 months after surgery when valves were explanted. Captured images showed a change in the profile opening and closing of valve prosthesis after lyophilization. The gradient measured (in vitro) in two valves was 17.08 +/- 0.57 and 18.76 +/- 0.70 mm Hg before lyophilization, and 34.24 +/- 0.59 and 30.40 +/- 0.97 mm Hg after lyophilization. Rehydration of both lyophilized valves was approximately 82%. Drying changed the profile of the opening and closing of valve prostheses, and increased on average by 83% the gradient in vitro tests. The result of the in vivo tests suggests maintaining pressure levels of the animal with the lyophilized prostheses within acceptable levels.

Cytotoxicity and Endothelial Cell Adhesion of Lyophilized and Irradiated Bovine Pericardium Modified With Silk Fibroin and Chitosan

Grafts of biological tissues have been used since the 1960s as an alternative to the mechanical heart prostheses. Nowadays, the most consolidated treatment to bovine pericardial (BP) bioprostheses is the crosslinking with glutaraldehyde (GA), although GA may induce calcification in vivo. In previous work, our group demonstrated that electron beam irradiation applied to lyophilized BP in the absence of oxygen promoted crosslinks among collagen fibers of BP tissue. In this work, the incorporation of silk fibroin (SF) and chitosan (CHIT) in the BP not treated with GA was studied. The samples were irradiated and then analyzed for their cytotoxicity and the ability of adhesion and growth of endothelial cells. Initially, all samples showed cytotoxicity. However, after a few washing cycles, the cytotoxicity due to acetic acid and ethanol residues was removed from the biomaterial making it suitable for the biofunctional test. The samples modified with SF/CHIT and electron beam irradiated favored the adhesion and growth of endothelial cells throughout the tissue.

Perfil ecocardiográfico do doente com estenose aórtica degenerativa

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular - Área de especialização: Ultrassonografia Cardiovascular.

Relationship of PON1 192 and 55 gene polymorphisms to calcific valvular aortic stenosis

Introduction and Objectives - Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical and pathophysiological risk factors of CAD and calcific aortic valve stenosis (CAVS), we postulated a link between PON1 alleles and CAVS progression. Methods - We investigated the association between PON1 55 and 192 single nucleotide polymorphisms (SNPs), their enzyme activity, and CAVS progression assessed by aortic valve area and transvalvular peak velocity in 67 consecutive patients with moderate CAVS and 251 healthy controls. Results - PON1 paraoxonase activity was higher in CAVS patients (P<0.001). The PON1 genotype Q192R SNP (P=0.03) and variant allele (R192) (P=0.01) frequencies differed between CAVS patients and controls. Significant association existed between PON1 enzyme activity, phenotypic effects of PON1 192 genotype polymorphisms, and CAVS progression, but not between PON1 55 and high-density lipoprotein (P=0.44) or low-density lipoprotein cholesterol (P=0.12), between 192 genotype and high-density lipoprotein (P=0.24) or low-density lipoprotein cholesterol (P=0.52). Conclusion - The PON1 genotype Q192R SNP has an important effect on CAVS disease progression. This study helps outline a genotype-phenotype relationship for PON1 in this unique population.

Mycoplasma pneumoniae and Chlamydia pneumoniae in calcified nodules of aortic stenotic valves

Aortic Valve Stenosis (AVS) has been explained as an atherosclerotic process of the valve as they often exhibit inflammatory changes with infiltration of macrophages, T lymphocytes and lipid infiltration. The present study investigated whether the bacteria Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP), detected previously in atherosclerotic plaques, are also present in AVS. Ten valves surgically removed from patients with AVS were analyzed by immunohistochemistry, in situ hybridization, and electron microscopy. The mean and standard deviation of the percentage areas occupied by CP antigens and MP - DNA were respectively 6.21 +/- 5.41 and 2.27 +/- 2.06 in calcified foci; 2.8 +/- 3.33 and 1.78+/- 3.63 in surrounding fibrotic areas, and 0.21 +/- 0.17 and 0.12 +/- 0.13 in less injured parts of the valve. There was higher amount of CP and MP in the calcified foci and in the surrounded fibrosis than in more preserved valvular regions. In conclusion, the fact that there were greater amounts of CP and MP in calcification foci of AVS favors the hypothesis that AS is not an inevitable degenerative process due to aging, but rather that it may be a response to the presence of these bacteria, similarly to the morphology detected in atherosclerosis damage.

Neonate Aortic Stenosis: Importance of Myocardial Perfusion in Prognosis

OBJECTIVE: To analyze our experience with percutaneous aortic balloon valvuloplasty in newborn infants with aortic stenosis, emphasizing the extraordinary importance of myocardial perfusion.METHODS: Over a 10-year-period, 21 neonates underwent percutaneous aortic balloon valvuloplasty. Age ranged from 2 to 27 days, weight ranged from 2.2 to 4.1 kg and 19 were males. All patients presented with congestive heart failure that could not be treated clinically. The onset of symptoms in the first week of life occurred in 9 patients considered as having critical aortic stenosis. Severe aortic stenosis occurred in 12 patients with the onset of symptoms in the second week of life.RESULTS: Mortality reached 100% in the patients with critical aortic stenosis. The procedure was considered effective in the 12 patients with severe aortic stenosis. Vascular complications included the loss of pulse in 12 patients and rupture of the femoral artery in 2 patients. Cardiac complications included acute aortic regurgitation in 2 patients and myocardial perforation in one. In an 8.2±1.3-year follow-up, 5 of the 12 patients died (2 patients due to septicemia and 3 patients due to congestive heart failure). Five of the other 7 patients underwent a new procedure and 2 required surgery.CONCLUSION: Percutaneous aortic valvuloplasty in neonates is not an effective procedure in the 1st week of life, because at this age the common presentation is cardiogenic shock. It is possible that, in those patients with critical aortic stenosis, dilation of the aortic valve during fetal life may change the prognosis of its clinical outcome.

Protective Effect of Aortic Stenosis on the Coronary Arteries. Hypothetic Considerations to an Old Enigma

Abstract A literature overview of angiographic studies has shown that the prevalence of significant coronary disease in patients with aortic stenosis (AS) varies from 20 to 60%. Early necropsy studies suggested that patients with AS had a lower than expected incidence of coronary artery disease (CAD), originating the concept of a protective effect of AS on the coronary arteries. The myth of AS protection against CAD would be better explained as endothelium-myocardial interaction (crosstalk) protection triggered by left ventricular overload. Therefore, the cGMP/NO pathway induced by the AS overload pressure would explain the low incidence of CAD, which is compatible with the amazing natural long-term evolution of this cardiac valve disease.

Traumatic mitral valve injury after blunt chest trauma: a case report and review of the literature.

Mitral valve injury after blunt chest trauma is a rare occurrence. We recently admitted a patient with severe traumatic mitral regurgitation who was successfully treated with surgery. Review of the literature aimed at taking an inventory of cases of traumatic nonpenetrating mitral insufficiency that were operated on, since the earliest report in 1964. Eighty-two cases were found and analyzed allowing for a better understanding of the epidemiology, etiology, natural history, pathology, and treatment of this rare condition. The most common lesions reach the papillary muscles (PM), followed by the chordae and then the mitral valve leaflets. Among the 82 cases reported that have been treated with surgery, 57% required a valve replacement. More than half of the patients had a PM injury with a complete or partial rupture. When the rupture is complete, and especially when it involves the anterior PM, the clinical picture is most always acute with clinically important hemodynamic repercussions, often necessitating emergency surgery, most of the time with mitral valve replacement. One must always suspect traumatic mitral injury after blunt chest trauma. The most common mitral lesions affect the PM. The clinical course can be indolent or devastating, and most often requires urgent or delayed surgical treatment, either with mitral valve repair or replacement.

Identification of reference genes for quantitative RT-PCR in ascending aortic aneurysms.

Hypertension and congenital aortic valve malformations are frequent causes of ascending aortic aneurysms. The molecular mechanisms of aneurysm formation under these circumstances are not well understood. Reference genes for gene activity studies in aortic tissue that are not influenced by aortic valve morphology and its hemodynamic consequences, aortic dilatation, hypertension, or antihypertensive medication are not available so far. This study determines genes in ascending aortic tissue that are independent of these parameters. Tissue specimens from dilated and undilated ascending aortas were obtained from 60 patients (age ≤70 years) with different morphologies of the aortic valve (tricuspid undilated n = 24, dilated n = 11; bicuspid undilated n = 6, dilated n = 15; unicuspid dilated n = 4). Of the studied individuals, 36 had hypertension, and 31 received ACE inhibitors or AT1 receptor antagonists. The specimens were obtained intraoperatively from the wall of the ascending aorta. We analyzed the expression levels of 32 candidate reference genes by quantitative RT-PCR (RT-qPCR). Differential expression levels were assessed by parametric statistics. The expression analysis of these 32 genes by RT-qPCR showed that EIF2B1, ELF1, and PPIA remained constant in their expression levels in the different specimen groups, thus being insensitive to aortic valve morphology, aortic dilatation, hypertension, and medication with ACE inhibitors or AT1 receptor antagonists. Unlike many other commonly used reference genes, the genes EIF2B1, ELF1, and PPIA are neither confounded by aortic comorbidities nor by antihypertensive medication and therefore are most suitable for gene expression analysis of ascending aortic tissue.

Mitral regurgitation.

Mitral regurgitation (MR) involves systolic retrograde flow from the left ventricle into the left atrium. While trivial MR is frequent in healthy subjects, moderate to severe MR constitutes the second most prevalent valve disease after aortic valve stenosis. Major causes of severe MR in Western countries include degenerative valve disease (myxomatous disease, flail leaflet, annular calcification) and ischaemic heart disease, while rheumatic disease remains a major cause of MR in developing countries. Chronic MR typically progresses insidiously over many years. Once established, however, severe MR portends a poor prognosis. The severity of MR can be assessed by various techniques, Doppler echocardiography being the most widely used. Mitral valve surgery is the only treatment of proven efficacy. It alleviates clinical symptoms and prevents ventricular dilatation and heart failure (or, at least, it attenuates further progression of these abnormalities). Valve repair significantly improves clinical outcomes compared with valve replacement, reducing mortality by approximately 70%. Reverse LV remodelling after valve repair occurs in half of patients with functional MR. Percutaneous, catheter-based to mitral valve repair is a novel approach currently under clinical scrutiny, with encouraging preliminary results. This modality may provide a valuable alternative to mitral valve surgery, especially in critically ill patients.

Resuscitated sudden cardiac death caused by left main coronary artery compression by an aneurysm of the sinus of Valsalva.

A 49-year-old woman, without known cardiovascular risk factors. Hoarseness of voice caused by a paralysis of left vocal cord. She was admitted to hospital because of acute coronary syndrome, associated to resuscitated cardiac arrest (asystolia documented) without later neurology sequels. Physical examination was anodyne. Echocardiographic study demonstrated a compatible image with a large left sinus of Valsalva aneurysm (SVA) (Panel A) and mild aortic regurgitation. Cardiac catheterization confirmed the presence of left SVA (Panel B) that produced extrinsic compression of the left main coronary artery (Panels C and D). Repair surgery was made by means of closing the aneurysmal orifice with a patch of dacron. Intra-operatory echocardiographic control study found severe aortic regurgitation, so valvular replacement with 19 mm mechanical prosthesis and extension of the valve annulus with patch of dacron was performed, associated with bypass with safena vein graft to left coronary artery. SVA is a very infrequent cardiac anomaly, generally with silent clinical course until it ruptures. Myocardial ischaemia caused by coronary artery compression is unusual. We described the case of a patient diagnosed of left SVA, whose initial clinical manifestation was the appearance of resuscitated sudden cardiac death in the context of an acute coronary syndrome.

Experience and intermediate-term results using the Contegra heterograft for right ventricular outflow reconstruction in adults.

OBJECTIVES: The Contegra bioprosthesis (valved heterologous bovine jugular vein) is used for reconstruction of the right ventricular outflow tract (RVOT) in congenital heart malformations and pulmonary valve replacement in different settings. Compared to pulmonary homografts, the Contegra conduit is readily available 'on the shelf'. So far, its use was mainly described in children. The aim of this study is to evaluate the feasibility and the outcome of Contegra graft implantation in the adult. METHODS: Between November 1999 and December 2007, a total of 32 Contegra grafts were implanted in 31 patients (24 men and 7 women), with a mean age of 35.7+/-10.5 years (range 18-54 years). All operations have been completed through median sternotomy with cardiopulmonary bypass. Indications included: Ross procedure for aortic valve disease (n=22); re-operation of corrected Fallot-tetralogy (n=5); isolated pulmonary valve disease (n=2); re-operation of double outlet right ventricle (DORV) (n=1); pulmonary stenosis in congenital dilated cardiomyopathy (DCM) (n=1). Conduit sizes included 22 mm (n=31), 20 mm (n=1). RESULTS: There was no hospital mortality and no valved conduit related early morbidity. In the median follow-up of 38 months (range 1-99 months) of 28 patients there was one late death, not conduit related (total mortality 3.6%). Re-operation for symptomatic graft stenosis was realised in two patients, 7 and 16 months after primo-implantation, corresponding to graft related late morbidity of 7.1%. CONCLUSIONS: In this small review of 32 operations using the Contegra graft for RVOT reconstruction in adult cardiac surgery for different indications, we observed good postoperative mid-term results concerning conduit function. Mean transpulmonary pressure gradients remain low (13.3+/-6.6 mmHg postoperative, 14.5+/-7.9 mmHg at follow-up). The use of the Contegra graft seems to be a good alternative to the homograft with low operative mortality and morbidity. Long-term outcome data are not available and further investigations must be performed to evaluate results.

Right-sided vegetation unmasks aortic endocarditis

Echocardiography is a key tool in the diagnosis of infective endocarditis. Although transthoracic echocardiography is the first step in the work-up, transoesophageal echocardiography is mandatory for the evaluation of the exact extent of the infectious process. Indeed, perivalvular abscess can fistulate towards different heart chambers, leading sometimes to critical clinical situations.

Eyes wide shut - unusual two stage repair of pectus excavatum and annuloaortic ectasia in a 37 year old marfan patient: Case report

We report about a 37 year old male patient with a pectus excavatum. The patient was in NYHA functional class III. After performed computed tomography the symptoms were thought to be related to the severity of chest deformation. A Ravitch-procedure had been accomplished in a district hospital in 2009. The crack of a metal bar led to a reevaluation 2010, in which surprisingly the presence of an annuloaortic ectasia (root 73 × 74 mm) in direct neighborhood of the formerly implanted metal-bars was diagnosed. Echocardiography revealed a severe aortic valve regurgitation, the left ventricle was massively dilated presenting a reduced ejection fraction of 45%. A marfan syndrome was suspected and the patient underwent a valve sparing aortic root replacement (David procedure) in our institution with an uneventful postoperative course. A review of the literature in combination with discussion of our case suggests the application of stronger recommendations towards preoperative cardiovascular assessment in patients with pectus excavatum.