Relationship between oxidative stress and three-dimensional echocardiographic changes in myxomatous mitral valves with severe regurgitation - a pilot study

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background. Reactive oxygen species (ROS) have been reported to contribute to the molecular pathogenesis of severe mitral regurgitation induced by myxomatous degeneration. Data about oxidative stress and the possible relationship with the extent of prolapsing and/or flail elements is scarce in the literature. The pathogenic mechanism may prompt the development of therapeutic approaches aimed at delaying extensive valvular alteration. Purpose. The aim of the study is to investigate the possible correlation between ROS expression in myxomatous mitral valves with severe regurgitation and the extent of valvular alteration. Material and methods. Samples from myxomatous mitral valves with ruptured chordae and severe regurgitation were harvested during surgical intervention for valve repair/replacement from 9 patients. Besides transthoracic echocardiography, all patients were evaluated before surgery by transesophageal echocardiography (TEE) with three-dimensional (3D) reconstruction of the mitral valve, using 3D zoom mode acquisition with qualitative and quantitative analysis through the 4D Auto MVQ technology. Tissue from the valvular samples was further analysed for the assessment of ROS by 2 methods: spectrophotometry (ferrous oxidation xylenol orange - FOX assay) and confocal microscopy (dihydroethidium staining). Results. Patients had a mean age of 51.88 ± 13.54 years, with a left ventricular ejection fraction of 62.55 ± 7.33%, left ventricular end-diastolic diameter of 5.4 ± 0.72cm and end-diastolic volume of 168.55 ± 62.57ml, a mitral annulus area of 17.91 ± 5.74 cm2 and a number of prolapsing/flail scallops varying between 1 and 5 (average of 2 ± 1 scallops). All patients had diffuse thickening of the mitral leaflets with at least one primary and one secondary ruptured chordae and flail of the P2 scallop. Two patients had significant prolapse of at least 2 anterior mitral leaflet scallops and three patients had supplemental significant prolapse and/or flail of at least 1 posterior scallop, besides flail of P2. The mean value for ROS in the valvular tissue was 9.46 ± 2.03nM H2O2/mg tissue/h at FOX assay. A significant positive correlation between the ROS values and the extent of prolapsing/flail segments was found (R = 0.67, p = 0.04). Conclusion. Besides the diagnosis and accurate preoperatory valve description, 3D TEE along with molecular investigations contribute to the understanding of myxomatous mitral valves’ pathogenesis. Oxidative stress increased in the mitral valves with advanced myxomatous degeneration. Whether this occurs as a cause or a consequence contributing to the disease progression as well as the sources of ROS are worth further investigation.