Relationship of Iron Deposition to Calcium Deposition in Human Aortic Valve Leaflets.

BACKGROUND: Intraleaflet hematomas are associated with advanced stages of aortic valve calcification and suspected to be involved in disease progression. However, the mechanism by which the entry of blood cells into the valves affects the biology of aortic valvular interstitial cells (VICs) remains to be elucidated. OBJECTIVES: This study sought to evaluate the putative link between intraleaflet hematoma and aortic valve calcification and to assess its pathophysiological implications. METHODS: The spatial relationship between calcium deposits and intraleaflet hematomas was analyzed by whole-mount staining of calcified and noncalcified human aortic valves, obtained in the context of heart transplantation and from patients who underwent surgical valve replacement. Endothelial microfissuring was evaluated by en face immunofluorescence and scanning electron microscopic analyses of the fibrosa surface. Red blood cell (RBC) preparations were used in vitro to assess, by immunofluorescence microscopy and Alizarin red staining, the potential impact of intraleaflet hematomas on phenotypic changes in VICs. RESULTS: Intraleaflet hematomas, revealed by iron deposits and RBCs into the fibrosa, secondary to endothelial microfissuring, were consistently found in noncalcified valves. The contact of primary VICs derived from these valves with RBCs resulted in a global inflammatory and osteoblastic phenotype, reflected by the up-regulation of interleukin-6, interleukin-1ß, bone sialoprotein, osteoprotegerin, receptor activator of nuclear factor kappa B, bone morphogenic protein 2, and muscle segment homeobox 2, the production of osteocalcin, and the formation of calcium deposits. CONCLUSIONS: The acquisition of an osteoblastic phenotype in VICs that come into contact with the senescent RBCs of intraleaflet hematomas may play a critical role in the initiation of calcium deposition into the fibrosa of human aortic valves.

Systematic transoesophageal echocardiography after mitral valve replacement: Rates and determinants of paravalvular regurgitation.

BACKGROUND: With the emergence of transcatheter mitral valve replacement, it appears crucial to provide contemporary references with which this new technology can be compared. At our institution, transoesophageal echocardiography is systematically performed before discharge after surgical mitral valve replacement. AIM: To evaluate the rate and determinants of paravalvular regurgitation after surgical mitral valve replacement. METHODS: We collected medical history, indication, type of surgery and in-hospital outcome in all consecutive patients who underwent a mitral valve replacement in the past 2 years at our institution. Paravalvular regurgitation was assessed semiquantitatively using transoesophageal echocardiography before discharge. RESULTS: We enrolled 399 patients (mean age 61±16 years; 58% women; 27% with a history of cardiac surgery). Mitral valve replacement was performed mainly for rheumatic disease (44%). Most patients were severely symptomatic (70% in New York Heart Association class III/IV). A mechanical prosthesis was implanted in 60% and a bioprosthesis in 40%. In-hospital mortality was 10%. Transoesophageal echocardiography was performed in 310 patients (77%); the main reasons for not performing transoesophageal echocardiography were frailty (n=40, 10%), early death (n=19, 5%) and contraindication for transoesophageal echocardiography (n=10, 3%). The overall rate of paravalvular regurgitation was 8% (n=25); a grade ≥2 was observed in five patients (2%), and two patients had to be reoperated on. Mitral annular calcification was the main factor associated with paravalvular regurgitation (P=0.01). CONCLUSIONS: Surgical mitral valve replacement was associated with significant in-hospital mortality and morbidity. Using systematic transoesophageal echocardiography assessment, paravalvular regurgitation was not uncommon (8%), and was significantly linked to mitral annulus calcification. However, clinically significant leakage (≥grade 2) was rare (2%).

Echocardiographic measurement of left atrial volume: Does the method matter?

BACKGROUND: Four two-dimensional echocardiographic methods (cube, ellipsoid, Simpson's and area-length) can be used to assess left atrial volume (LAV). AIMS: To compare absolute LAV measurements and evaluate agreement regarding the semiquantitative assessment of degree of left atrial (LA) enlargement, between methods. METHODS: We prospectively measured LAV in 51 healthy volunteers using the four methods, and defined thresholds for moderate (mean+2 standard deviations [SDs]) and severe (mean+4 SDs) LA enlargement for each method. In 372 patients referred for echocardiography, we compared absolute LAV measurements and agreement between methods. RESULTS: LAV was significantly different between methods in the healthy volunteer group (11 ± 4, 17 ± 3, 26 ± 6 and 28 ± 7 mL/m(2), respectively; P<0.0001), resulting in different thresholds for moderate and severe LA enlargement. LAV was also significantly different in the 372 patients (30 ± 20, 47 ± 27, 61 ± 34 and 65 ± 36 mL/m(2), respectively; P<0.0001). Agreement regarding degree of LA enlargement (none, moderate, severe), using the area-length method as reference, was modest with the cube method (kappa=0.41), correct with the ellipsoid method (kappa=0.60) and excellent with Simpson's method (kappa=0.83). CONCLUSION: The choice of the method had a major effect on assessment of degree of LA enlargement. Our results suggest that the cube and ellipsoid methods, which significantly underestimated LAV and provided modest agreement, should be disregarded. In contrast, Simpson's method and the area-length method were slightly different, but showed close agreement, and should be preferred, using dedicated thresholds (50 and 56 mL/m(2) respectively).