Eleonora Piasentini

Ascending aorta diameters measured by echocardiography using both leading edge-to-leading edge and inner edge-to-inner edge conventions in healthy volunteers

AIMS Reference ranges of ascending aorta diameters (AAoD) for two-dimensional echocardiography (2DE) using inner edge (IE) convention are lacking, preventing the comparison of AAoD measurements by 2DE with those obtained by other imaging modalities. METHODS AND RESULTS We used harmonic imaging 2DE to prospectively study 218 healthy volunteers (56% women, 42 ± 15 years, 18-80 years). Measurements were performed at the level of aortic root (AoR), sinotubular junction (STJ), and proximal tubular portion (TAo, 1 cm from the STJ) using both leading edge (LE) and IE conventions at end-diastole and end-systole. Feasibility of AAoD measurements between end-diastole and end-systole was similar at AoR and STJ levels, but it was significantly different at TAo level (82 vs. 96%, respectively, P < 0.0001). Ascending aorta diameters indexed to height were larger in men than in women (P < 0.0001). After adjusting for the effect of gender, only age and body surface area (BSA) were independent predictors of AAoD at multivariable analysis. Average end-diastolic AoR, STJ, and TAo diameters measured using IE convention were similar between genders (17 ± 2, 15 ± 2, and 15 ± 2 mm/m(2), respectively). Corresponding AAoD measured using the LE convention were 18 ± 2, 16 ± 2, and 17 ± 4 mm/m(2), respectively. On average, the end-systolic AAoD measured using LE were 2 mm larger than those performed using IE or at end-diastole. Mean aortic wall thickness was 2.4 ± 0.8 mm. CONCLUSION End-diastolic AAoD measured using IE were significantly smaller than those obtained either using LE convention or at end-systole. Gender-specific reference values for AAoD indexed for BSA should be used to identify ascending aorta pathology.

Cardiac sympathetic neurons provide trophic signal to the heart via β2-adrenoceptor-dependent regulation of proteolysis

AIMS Increased cardiac sympathetic neuron (SN) activity has been associated with pathologies such as heart failure and hypertrophy, suggesting that cardiac innervation regulates cardiomyocyte trophism. Whether continuous input from the SNs is required for the maintenance of the cardiomyocyte size has not been determined thus far. METHODS AND RESULTS To address the role of cardiac innervation in cardiomyocyte size regulation, we monitored the effect of pharmacological sympathetic denervation in mice on cardiac structure, function, and signalling from 24 h to 30 days in the absence of other pathological stimuli. SN ablation caused an immediate reduction in the cardiomyocyte size with minimal consequences on the resting contractile function. Atrophic remodelling was mediated by the ubiquitin-proteasome system through FOXO-dependent early induction of the muscle-specific E3 ubiquitin ligases Atrogin-1/MAFbx and MuRF1, which was followed by activation of the autophagy-lysosome system. MuRF1 was found to be determinant in denervation atrophy as remodelling did not develop in denervated MuRF1 knock-out (KO) hearts. These effects were caused by decreased basal stimulation of cardiomyocyte β2-adrenoceptor (AR), as atrophy was prevented by treatment of denervated mice with the β2-AR agonist clenbuterol. Consistent with these data, we also observed that β2-AR KO mice showed cardiac atrophy at rest. CONCLUSION Cardiac SNs are strong regulators of the cardiomyocyte size via β2-AR-dependent repression of proteolysis, demonstrating that the neuro-cardiac axis operates constitutively for the determination of the physiological cardiomyocyte size. These results are of great clinical relevance given the role of β-AR in cardiovascular diseases and their modulation in therapy.

Quantitative analysis of mitral annular geometry and function in healthy volunteers using transthoracic three-dimensional echocardiography.

BACKGROUND Quantitative assessment of the mitral annulus provides information regarding the pathophysiology of mitral regurgitation and aids in the planning of reparative surgery. Three-dimensional (3D) transthoracic echocardiographic data sets acquired with current scanners have enough spatial and temporal resolution to allow the quantitative analysis of the mitral annulus. Accordingly, the authors performed (1) a validation study to assess the agreement of quantitative analysis of the mitral annulus performed on 3D transthoracic echocardiography (TTE) and 3D transesophageal echocardiography (TEE) and (2) a normative study to obtain the reference values of 3D transthoracic echocardiographic parameters for mitral annular (MA) geometry and dynamics. METHODS Mitral valve data sets were obtained by 3D TEE and 3D TTE in 30 consecutive patients with clinically indicated TEE (validation study) and 3D TTE in 224 healthy volunteers (aged 18-76 years) (normative study). RESULTS In the validation study, MA measurements obtained by 3D TTE were similar to those obtained by 3D TEE (P = NS). In the normative study, MA analysis by 3D TTE was feasible (94.5%) and reproducible (intraclass correlation coefficient = 0.78-0.97). MA diameters, area, and circumference were correlated with body surface area (r > 0.50 for all) but not with age. Men had larger MA areas than women (4.9 ± 1.0 vs 4.5 ± 0.7 cm(2)/m(2), P = .004). During systole, MA area decreased by 29 ± 5%. This decrease was related mainly to anteroposterior diameter shortening (20 ± 7%). CONCLUSIONS MA quantitative analysis by 3D TTE was accurate compared with 3D TEE in unselected patients with mitral valve disease. In healthy subjects, it was highly feasible and reproducible. The availability of reference values for MA geometry and dynamics may foster the implementation of MA quantitative analysis by 3D TTE in clinical settings.

Relationship between mitral annulus function and mitral regurgitation severity and left atrial remodelling in patients with primary mitral regurgitation

AIMS To explore the relationship between the mitral annular (MA) remodelling and dysfunction, mitral regurgitation (MR) severity, left ventricular (LV) and atrial (LA) size and function in patients with organic MR (OMR). METHODS AND RESULTS A total of 52 patients (57 ± 15 years, 31 men) with mild to severe OMR and 52 controls underwent 3D transthoracic echocardiography acquisitions of the mitral valve (MV), LA, and LV. MA geometry and dynamics, LV and LA volumes, LV ejection fraction (LVEF) and emptying fractions (LAEF) were assessed using dedicated software packages. LA and LV myocardial deformations were assessed using 2D speckle-tracking echocardiography. OMR patients presented larger and more spherical MA than controls during the entire systole (P < 0.001). Although the MA non-planarity at early-systole was similar between OMR and controls (157 ± 13° vs. 153 ± 12°, P = NS), the MA became flatter from mid- to end-systole (153 ± 12 vs. 146 ± 10° and 157 ± 12 vs. 147 ± 8°, P < 0.01) in OMR. MA area fractional change was lower in patients with OMR (22 ± 5% vs. 28 ± 5%, P < 0.001), and correlated with the MR orifice and volume (r = -0.52 and r = -0.55). MA fractional area change correlated with LA minimum and maximum volumes (r = 0.77 and r = 0.70), total and active LAEF (r = 0.72 and r = 0.76), and LA negative strain and strain rate (r = 0.52 and r = 0.57), but not with the LVEF or LV global longitudinal strain. In a multivariate regression model using LAEF and LVEF, solely active LAEF correlated with the MA fractional area change (β = 0.51, P = 0.005). CONCLUSION In patients with OMR, MA reduced function correlates with the MR severity and the LA size and function, but not with the LV function.