A clinical perspective on the utility of alpha 1 antichymotrypsin for the early diagnosis of calcific aortic stenosis.

BACKGROUND: Calcific aortic stenosis (CAS) is the most common heart valve disease in the elderly, representing an important economic and social burden in developed countries. Currently, there is no way to predict either the onset or progression of CAS, emphasizing the need to identify useful biomarkers for this condition. METHODS: We performed a multi-proteomic analysis on different kinds of samples from CAS patients and healthy donors: tissue, secretome and plasma. The results were validated in an independent cohort of subjects by immunohistochemistry, western blotting and selected reaction monitoring. RESULTS: Alpha 1 antichymotrypsin (AACT) abundance was altered in the CAS samples, as confirmed in the validation phase. The significant changes observed in the amounts of this protein strongly suggest that it could be involved in the molecular mechanisms underlying CAS. In addition, our results suggest there is enhanced release of AACT into the extracellular fluids when the disease commences. CONCLUSIONS: The significant increase of AACT in CAS patients suggests it fulfils an important role in the physiopathology of this disease. These results permit us to propose that AACT may serve as a potential marker for the diagnosis of CAS, with considerable clinical value.

A comprehensive study of calcific aortic stenosis: from rabbit to human samples.

The global incidence of calcific aortic stenosis (CAS) is increasing owing, in part, to a growing elderly population. The condition poses a great challenge to public health, because of the multiple comorbidities of these older patients. Using a rabbit model of CAS, we sought to characterize protein alterations associated with calcified valve tissue that can be ultimately measured in plasma as non-invasive biomarkers of CAS. Aortic valves from healthy and mild stenotic rabbits were analyzed by two-dimensional difference gel electrophoresis, and selected reaction monitoring was used to directly measure the differentially expressed proteins in plasma from the same rabbits to corroborate their potential as diagnostic indicators. Similar analyses were performed in plasma from human subjects, to examine the suitability of these diagnostic indicators for transfer to the clinical setting. Eight proteins were found to be differentially expressed in CAS tissue, but only three were also altered in plasma samples from rabbits and humans: transitional endoplasmic reticulum ATPase, tropomyosin α-1 chain and L-lactate dehydrogenase B chain. Results of receiver operating characteristic curves showed the discriminative power of the scores, which increased when the three proteins were analyzed as a panel. Our study shows that a molecular panel comprising three proteins related to osteoblastic differentiation could have utility as a serum CAS indicator and/or therapeutic target.

Chronic Type A Aortic Dissection and Giant Aortic Root Aneurysm After Aortic Valve Replacement.

We describe the case of a 61-year-old male with a giant aortic root aneurysm associated with chronic aortic Type A dissection. The patient had been operated on 16 years before due to aortic annuloectasia with mechanical valve replacement. The patient underwent revision aortic surgery with a Bentall-De Bono operation with Svensson modification, using a #21 On-X Valsalva mechanical valve conduit. The postoperative course was uneventful.

iTRAQ proteomic analysis of extracellular matrix remodeling in aortic valve disease.

Degenerative aortic stenosis (AS) is the most common worldwide cause of valve replacement. The aortic valve is a thin, complex, layered connective tissue with compartmentalized extracellular matrix (ECM) produced by specialized cell types, which directs blood flow in one direction through the heart. There is evidence suggesting remodeling of such ECM during aortic stenosis development. Thus, a better characterization of the role of ECM proteins in this disease would increase our understanding of the underlying molecular mechanisms. Aortic valve samples were collected from 18 patients which underwent aortic valve replacement (50% males, mean age of 74 years) and 18 normal control valves were obtained from necropsies (40% males, mean age of 69 years). The proteome of the samples was analyzed by 2D-LC MS/MS iTRAQ methodology. The results showed an altered expression of 13 ECM proteins of which 3 (biglycan, periostin, prolargin) were validated by Western blotting and/or SRM analyses. These findings are substantiated by our previous results demonstrating differential ECM protein expression. The present study has demonstrated a differential ECM protein pattern in individuals with AS, therefore supporting previous evidence of a dynamic ECM remodeling in human aortic valves during AS development.

Left ventricular-coronary sinus/right ventricular fistula late after mitral valve replacement.

Development of an intracardiac fistula is a rare complication after mitral valve replacement. In the literature we have found six cases of left ventricular-coronary sinus fistula and another one of left ventricular-coronary sinus and right atrial fistula. We report the history and course of a patient in whom a left ventricular-coronary sinus and right ventricular fistula developed late after mitral valve replacement. The current study examines this type of intracardiac shunt, and presents our report on a left ventricular-coronary sinus and right ventricular fistula complication.

Endocarditis con hemocultivos negativos: infección por Mycoplasma hominis / Culture-negative Endocarditis: mycoplasma hominis Infection

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[Prophylaxis of sternal dehiscence in obese patients through systematic application of Robicsek closure]. / Profilaxis de la dehiscencia esternal en obesos mediante la aplicación sistemática del cerclaje de tipo Robicsek.

INTRODUCTION: Sternal dehiscence is a relatively frequent complication in median sternotomy and causes high morbidity and mortality in cardiothoracic surgery. Obesity is one of the most important risk factors for sternal infection and dehiscence and its prevalence is increasingly frequent in patients undergoing cardiac surgery. The aim of the present study was to assess the clinical benefit of the prophylactic use of Robicsek sternal reinforcement in high-risk patients undergoing cardiac surgery. PATIENTS AND METHOD: Two hundred ninety consecutive patients who underwent median sternotomy in our center were analyzed. The indications for prophylactic sternal reinforcement were severe sternal osteoporosis or a body mass index (BMI) of > or = 30. The technique was used in 105 patients, 54 men and 51 women, with a mean age of 67.7 +/- 9.1 years and a mean BMI of 31.8 +/- 4.1. RESULTS: None of the patients in the reinforcement group developed noninfectious dehiscence; only one patient (1.7%) in this group showed sternal dehiscence due to osteomyelitis with good response to surgical debridement and intravenous antibiotics. CONCLUSION: Robicsek reinforcement reduces the incidence of sternal dehiscence in high-risk patients and its prophylactic use should be considered in patients with severe osteoporosis or a BMI of > or = 30.

Profilaxis de la dehiscencia esternal en obesos mediante la aplicación sistemática del cerclaje de tipo Robicsek / Prophylaxis of sternal dehiscence in obese patients through systematic application of robicsek closure

Introducción. La dehiscencia esternal es una complicación relativamente frecuente de la esternotomía media y que causa gran morbimortalidad en cirugía cardiotorácica. La obesidad se considera uno de los factores de riesgo más importantes de dehiscencia e infección esternal, y su prevalencia cada vez mayor en la población sometida a cirugía cardíaca. En el presente estudio se evalúa el beneficio clínico del uso profiláctico del refuerzo esternal de tipo Robicsek en los pacientes de alto riesgo que son intervenidos de cirugía cardíaca mayor. Pacientes y método. Se analiza a 290 pacientes consecutivos intervenidos mediante esternotomía media en nuestro centro. La indicación de refuerzo profiláctico esternal se estableció en casos de osteoporosis esternal severa o índice de masa corporal (IMC) >= 30, empleándose la técnica en 105 pacientes, 54 varones y 51 mujeres, cuya edad media era de 67,7 ± 9,1 años y con un IMC medio de 31,8 ± 4,1. Resultados. No hubo dehiscencias no infecciosas en el grupo con refuerzo de tipo Robicsek; sólo se produjo un caso (1,7%) de dehiscencia esternal debida a osteomielitis en el grupo reforzado, con buena respuesta a desbridamiento quirúrgico asociado con antibioterapia por vía intravenosa. Conclusión. El refuerzo de tipo Robicsek reduce la incidencia de dehiscencia esternal en los pacientes de alto riesgo y su indicación profiláctica debe ser considerada en casos de osteroporosis severa o IMC >= 30 (AU)

Introduction. Sternal deshidence is a relatively frequent complication in median sternotomy and causes high morbidity and mortality in cardiothoracic surgery. Obesity is one of the most important risk factors for sternal infection and deshidence and its prevalence is increasingly frequent in patients undergoing cardiac surgery. The aim of the present study was to assess the clinical benefit of the prophylactic use of robicsek sternal reinforcement in high-risk patients undergoing cardiac surgery. Patient and method. Two hundred ninety ninety consecutive patients who underwent median sternotomy in our center were analysed. The indications for prophylactic sternal reinforcement were severe sternal osteoporosis or a body mass indez (BMI) of >= 30. The technique was used in 105 patients, 54 men and 51 women, with a mean age of 67.7 +/- 9.1 years and a mean BMI of 31.8+/-4.1. Results. None of the patients in the reinforcement group developed non-infectious dehiscence; only one patient (1.7%) in this group showed sternal dehiscence due to osteomyelitis with good response to surgical debridement and intravenous antibiotics. Conclusion. Robicsek reinforcement reduces the incidence of sternal dehiscence in high-risk patients and its prophylactic use should be considered in patients with severe osteoporosis or a BMI of >=30 (AU)