Calcific Aortic Valve Stenosis and Atherosclerotic Calcification.

PURPOSE OF REVIEW: This review summarizes the pathophysiology of calcific aortic valve stenosis (CAVS) and surveys relevant clinical data and basic research that explain how CAVS arises. RECENT FINDINGS: Lipoprotein(a) [Lp(a)], lipoprotein-associated phospholipase A2 (Lp-PLA2), oxidized phospholipids (OxPL), autotaxin, and genetic driving forces such as mutations in LPA gene and NOTCH gene seem to play a major role in the development of CAVS. These factors might well become targets of medical therapy in the coming years. CVAS seems to be a multifactorial disease that has much in common with coronary artery disease, mainly regarding lipidic accumulation and calcium deposition. No clinical trials conducted to date have managed to answer the key question of whether Lp(a) lowering and anti-calcific therapies confer a benefit in terms of reducing incidence or progression of CAVS, although additional outcome trials are ongoing.

Pre- and post-surgical evaluation of the inflammatory response in patients with aortic stenosis treated with different types of prosthesis.

BACKGROUND: The inflammatory process in aortic valvular stenosis persists after surgery to replace the valve in almost half of the patients. No association has been found to its persistence. The main objective of this study was to evaluate the inflammatory response in patients with aortic stenosis through the determination of several biomarkers in plasma measured before and after the valvular replacement and to seek an association with the type of prosthesis used. METHODS: This is an observational study with a follow up of 6 months in subjects with severe aortic stenosis. Seric concentrations of TNFa, IL-1, IL-6 and ICAM and echocardiographic variables were quantified previous to the surgery and a week and 6 months after it. A group of control subjects paired by age and gender was included. RESULTS: Seventy-nine subjects were studied of which 57% were male; the average age was of 59 (± 11.4) years. Previous to surgery, the concentration of cytokines was higher in patients than in control subjects. A biological prosthesis was implanted in 48 patients and a mechanical prosthesis in 31. Both, types of prosthesis have components made of titanium. The echocardiograms 1 week and 6 months after the surgery showed a decrease in the mean aortic gradient and an increase in the valvular area (p = 0.001). Half of the patients still showed high proinflammatory cytokine levels. There were no differences according to the type of prosthesis implanted after adjustments for demographic variables, comorbidities and echocardiographic data. CONCLUSIONS: The inflammatory response caused by both types of valvular prothesis at 6 months after implantation were similar. Both types of prosthesis are recommended, they had similarities in hemodynamic profiles registered with Doppler echocardiography. Age of the patient or the suitability use of anticoagulants determines the type of prosthesis to be used.

Decreased levels of soluble receptor for advanced glycation end-products in aortic valve calcification patients.

The soluble receptor for advanced glycation end-products (sRAGE) shows a close relationship with atherosclerosis. The goal of this study was to compare the levels of sRAGE in patients with and without aortic valve calcification and to investigate the relationship between them. After transthoracic echocardiographic examination, 120 male patients with aortic valve calcification and 120 age-matched male controls without aortic valve calcification were included in our study. sRAGE levels were compared between groups. The prevalence of diabetes mellitus and coronary artery disease were significantly higher in the aortic valve calcification group than in the control group (63.3 versus 45%, P = 0.01, and 65 versus 51.7%, P < 0.01, respectively). The levels of sRAGE were lower in the aortic valve calcification group than in the control group (203.8 ± 34.6 versus 324.7 ± 41.6 pg/mL, P < 0.01). In multivariate analysis, age, coronary artery disease, and sRAGE levels were independent predictors of aortic valve calcification. Our study demonstrates that sRAGE, which was proven to be a potential marker of atherosclerosis, might have a role in the development of aortic valve calcification.

Função diastólica na estenose aórtica: correlação com NT-ProBNP e remodelamento pós-operatório / Correlation to NT-ProBNP and remodeling after cardiac surgery

FUNDAMENTO: A função diastólica em portadores de estenose aórtica (EAO) é pouco estudada. Não é possível estabelecer uma possível correlação entre biomarcadores e disfunção diastólica. OBJETIVO: Avaliar a função diastólica em portadores de EAO submetidos à troca valvar através de ecocardiografia transtorácica e correlacionar com valores de NT-proBNP. MÉTODOS: Estudamos 31 pacientes com EAO (11 homens), com idade entre 21 e 81 anos (média de 61±15 anos), submetidos a tratamento cirúrgico de EAO. Foi realizada dosagem sérica de NT-proBNP e o resultado, comparado com variáveis ecocardiográficas obtidas pelo Doppler pulsado em fluxo mitral, Doppler pulsado em veias pulmonares e Doppler tecidual, tanto no pré quanto no pós-operatório. RESULTADOS: Observou-se melhora na Fração de Ejeção (FE) de AE e Tempo de Relaxamento Isovolumétrico (TRIV), além de redução nos seguintes parâmetros: a) Relação da velocidade diastólica precoce mitral (onda E) com a velocidade do anel mitral (onda E´) (E/E'), b) Volume sistólico de átrio esquerdo (AE), c) Volume sistólico de AE indexado, d) Diâmetro diastólico de ventrículo esquerdo (DDVE), e) Diâmetro sistólico de VE (DSVE), f) Volume diastólico final (VDF), g) Massa indexada de VE e h) Relação Volume/Massa de ventrículo esquerdo (VE). Os valores do NT-proBNP correlacionaram-se de modo positivo com os diversos graus de disfunção diastólica, tanto no pré como no pós-operatório. CONCLUSÃO: 1) A cirurgia de troca valvar para correção de EAO resultou em melhora significativa da função diastólica ventricular. 2) Os valores de NT-proBNP correlacionaram-se positivamente com as variáveis ecocardiográficas que determinam disfunção diastólica, sendo o NT-proBNP um bom marcador para caracterizar essa disfunção em portadores de EAO.

BACKGROUND: Few data are available on diastolic function in patients with aortic stenosis (AOS) with indication of surgical treatment. A potential correlation between biomarkers and diastolic function has not been established. OBJECTIVE: The aim of our study was to evaluate diastolic function in patients with AOS waiting for aortic valve replacement (AVR) echocardiographically, and to verify its correlation with serum brain natriuretic peptide (NT-proBNP). METHODS: Thirty-one AOS patients (11 male), 21 to 81 years old (mean age, 61±15 years old) were studied before and after AVR. Diastolic function was assessed with Doppler methods: transvalvar mitral flow, tissue Doppler imaging (TDI) and pulmonary venous Doppler (PVD), correlating with serum brain natriuretic peptide (NT-proBNP) before and 6 months after AVR. RESULTS: Comparing pre to post-operative period, we observed an increase of the left atrial ejection fraction and isovolumetric relaxation time (IRT), and the decrease of the mitral velocity to early diastolic velocity of the mitral annulus ratio (E/E'), the difference between the pulmonary A wave duration and mitral A duration, left atrial systolic volume, left atrial systolic volume index, left ventricular diastolic diameter, left ventricular systolic diameter, end diastolic volume (LVEDV), left ventricular mass index, left ventricular volume and mass index ratio. The values of NT-proBNP were positively correlated to diastolic dysfunction, both before and after surgery. CONCLUSION: AOS patients' ventricular diastolic function improved after AVR. The biomarker NT-proBNP might be a useful biomarker of diastolic function in these patients, before and after AVR. NT-proBNP values show a positive correlation with echocardiographic variables that determine diastolic dysfunction, and is a good marker for the characterization of this dysfunction in AOS patients.

Correlation to NT-ProBNP and remodeling after cardiac surgery.

BACKGROUND: Few data are available on diastolic function in patients with aortic stenosis (AOS) with indication of surgical treatment. A potential correlation between biomarkers and diastolic function has not been established. OBJECTIVE: The aim of our study was to evaluate diastolic function in patients with AOS waiting for aortic valve replacement (AVR) echocardiographically, and to verify its correlation with serum brain natriuretic peptide (NT-proBNP). METHODS: Thirty-one AOS patients (11 male), 21 to 81 years old (mean age, 61±15 years old) were studied before and after AVR. Diastolic function was assessed with Doppler methods: transvalvar mitral flow, tissue Doppler imaging (TDI) and pulmonary venous Doppler (PVD), correlating with serum brain natriuretic peptide (NT-proBNP) before and 6 months after AVR. RESULTS: Comparing pre to post-operative period, we observed an increase of the left atrial ejection fraction and isovolumetric relaxation time (IRT), and the decrease of the mitral velocity to early diastolic velocity of the mitral annulus ratio (E/E'), the difference between the pulmonary A wave duration and mitral A duration, left atrial systolic volume, left atrial systolic volume index, left ventricular diastolic diameter, left ventricular systolic diameter, end diastolic volume (LVEDV), left ventricular mass index, left ventricular volume and mass index ratio. The values of NT-proBNP were positively correlated to diastolic dysfunction, both before and after surgery. CONCLUSION: AOS patients' ventricular diastolic function improved after AVR. The biomarker NT-proBNP might be a useful biomarker of diastolic function in these patients, before and after AVR. NT-proBNP values show a positive correlation with echocardiographic variables that determine diastolic dysfunction, and is a good marker for the characterization of this dysfunction in AOS patients.

Aortic stenosis and acquired von Willebrand disease: lack of association.

OBJECTIVES: The association between aortic stenosis (AS) and acquired von Willebrand disease type 2A has been described. It may be present in up to 90% of patients with AS. Shear stress has been proposed as the underlying mechanism; however, the physiopathology of this condition is not completely understood. No specific treatment has been studied in this specific population besides aortic valve replacement (AVR). As a coadjuvant therapy, some cardiac surgery centers use desmopressin routinely. The authors report the first stage of an ongoing study designed to compare the effects of desmopressin versus placebo in patients with severe AS scheduled for AVR. Because of the different incidences of the acquired von Willebrand type 2A reported in the literature, the first stage was conducted to describe the incidence of this clinical association in the present population, allowing the sample size for the second stage of the study to be obtained. DESIGN: A prospective cohort study. SETTING: A single academic medical center. PARTICIPANTS: Thirteen patients with severe AS scheduled for AVR. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients with severe AS scheduled for AVR were studied preoperatively with a von Willebrand laboratory panel. Results were negative for acquired von Willebrand disease type 2A in all patients. The second stage of the trial was stopped. CONCLUSION: Contrary to previous reports, no correlation was found between AS and acquired von Willebrand disease type 2A. Further studies are needed to ascertain whether this lack of association is caused by a specific characteristic of the present population, the small sample size, or other factors.

Incidência de distúrbios da condução atrioventricular e intraventricular após implante percutâneo da bioprótese valvar aórtica CoreValve / Incidence of atrioventricular and intraventricular conduction disorders after transcatheter aortic valve implantation with the CoreValve bioprosthesis

Introdução: O sistema de condução localizado no septo interventricular encontra-se anatomicamente contíguo ao anel valvar aórtico. Por isso, distúrbios na condução atrioventricular e intraventricular podem decorrer de inflamação, edema e estresse mecânico causados pelas hastes metálicas da bioprótese CoreValve. O objetivo deste estudo foi avaliar a incidência de distúrbios da condução atrioventricular e intraventricular após implante percutâneo da CoreValve. Método: Entre janeiro de 2008 e abril de 2010, 23 pacientes portadores de estenose aórtica foram submetidos a implante da CoreValve. A média de idade foi de 81 ± 8,3 anos, e 12 (52,1%) pacientes eram do sexo masculino. Resultados: Após o implante valvar, constataram-se as seguintes alterações na condução atrioventricular: 3 (13%) bloqueios atrioventriculares totais, 2 (8,7%) bloqueios atrioventriculares de 2º grau e 8 (34,8%) bloqueios atrioventriculares de 1º grau, sendo 4 (17,4%) novos e 4 preexistentes. Assim, distúrbios de condução mais avançados, como bloqueio atrioventricular de 2o grau e/ou bloqueio atrioventricular total ocorreram em 5 (21,7%) pacientes. Em relação aos distúrbios da condução intraventricular pós-implante, foram detectados 14 (60,9%) bloqueios completos de ramo esquerdo, sendo 2 (8,7%) com bloqueio completo de ramo direito e bloqueio completo de ramo esquerdo alternante. Nesta série, 7 (30,4%) pacientes foram submetidos a implante de marca-passo permanente, 6 (26,1%) deles por indicação absoluta. Todos os pacientes que apresentavam bloqueio completo de ramo direito antes do procedimento necessitaram do marca-passo permanente...

Background: There is a close anatomical relationship between the aortic valve annulus and the conduction system.Therefore, atrioventricular and intraventricular conduction disorders may occur as a result of inflammation, edema and mechanical stress caused by the metallic struts of the CoreValvebioprosthesis. The objective of this study was to evaluate the incidence of atrioventricular and intraventricular conduction disorders after percutaneous CoreValve implantation.Method: Between January 2008 and April 2010, 23 patients with aortic stenosis were submitted to CoreValve bioprosthesis implantation. Mean age was 81 ± 8.3 years and 12 (52.1%) patients were male. Results: After valve implantation, the following atrioventricular conduction disorderswere observed: 3 (13%) complete atrioventricular blocks, 2 (8.7%) 2nd degree atrioventricular blocks and 8 (34.8%) 1st degree atrioventricular blocks, of which 4 (17.4%) werenew and 4 were preexisting. Therefore, advanced conduction disorders, such as 2nd degree atrioventricular block and/orcomplete atrioventricular block were observed in 5 (21.7%) patients. As to post-implant intraventricular conductiondisorders, 14 (60.9%) left bundle branch blocks were observed, 2 (8.7%) of them with alternating right bundle branch block and left bundle branch block. In this series, 7 (30.4%) patients received a permanent pacemaker, 6 (26.1%) of them with absolute indication. All of the patients withright bundle branch block before the procedure required permanent pacemaker implantation. Conclusion: Atrioventricular conduction disorders and, specially, left bundle branch block are common after percutaneous implantation of the CoreValve prosthesis. Permanent pacemaker is required in approximately one fourth of the cases. The presence of pre-implant right bundle branch block is related to a greater risk of developing advanced conduction disorders.

Gastrointestinal bleeding diagnosed by red blood cell scintigraphy in a patient with aortic stenosis: a case of Heyde syndrome.

The authors report a case of small bowel bleeding diagnosed by Tc-99m-labeled red blood cell (RBC) scintigraphy during the postoperative period after aortic valve replacement. There is a relationship between aortic valve stenosis and gastrointestinal bleeding in elderly patients, called Heyde syndrome. The described patient had chronic anemia that worsened after surgery. RBC scintigraphy localized the source of bleeding from jejunal angiodysplasia confirmed by mesenteric angiography. This case illustrates the diagnostic information provided by RBC scintigraphy in this syndrome.