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Advanced pharmacologic and interventional therapies have improved survival in heart failure. Implantable cardioverter-defibrillators (ICD) have been shown to reduce mortality in patients with heart failure, but the benefit appears to be uneven in this population. We reviewed the evidence showing the benefit of ICD therapy in heart failure patients, the main issues arising from these studies, and the possible answers for a better risk stratification. In addition, we showed that multimodality imaging could improve patient selection for the implantation of ICDs, in both primary and secondary prevention, beyond the selection using only the left ventricular ejection fraction, by concentrating on arrhythmic substrate.

Background LV volumes and LVEF measured by 3DE are more accurate and repeatable than those calculated with 2DE. However, the added prognostic value of 3DE LV volumes and EF remains to be clarified. Objectives To analyze if the left ventricular (LV) volumes and ejection fraction (EF) measured by three-dimensional echocardiography (3DE) have an incremental prognostic value over measurements obtained from two-dimensional echocardiography (2DE) in patients referred to a high-volume echocardiography laboratory. Methods We measured LV volumes and EF using both 2DE and 3DE in 725 consecutive patients (67% men; 59±18 years) with various clinical indications referred for a routine clinical study. Results LV volumes were significantly larger, and EF was lower when measured by 3DE than 2DE. During follow-up (3.6±1.2 years), 111 (15.3%) all-cause deaths and 248 (34.2%) cardiac hospitalizations occurred. Larger LV volumes and lower EF were associated with worse otcome independent of age, creatinine, hemoglobin, atrial fibrillation, and ischemic heart diseases). In stepwise Cox regression analyses, the association of both death and cardiac hospitalization with clinical data (CD: age, creatinine, hemoglobin, atrial fibrillation and ischemic heart disease) whose Harrel's C-index (HC) was 0.775, were augmented more by the LV volumes and EF obtained by 3DE than by 2DE parameters. The association of CD with death was not affected by LV end-diastolic volume (EDV) either measured by 2DE or 3DE. Conversely, it was incremented by 3DE LVEF (HC= 0.84, p Conclusions 3DE LVEF and ESV showed stronger association with outcome than 2DE parameters LVEF measured by 3DE had a prognostic discriminatory power than 2D LVEF. Moreover, 3DE LV volumes threshold values for LV dilation had a higher discriminatory power and prognostic value than the corresponding 2DE values reported in current guidelines.

Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (RCHOP) chemotherapy in non-Hodgkin's lymphoma (NHL) has risk of cardiotoxicity.To determine the role of myocardial work and biomarkers in subclinical diagnosis and prediction of cardiotoxicity.The 130 NHL patients (52 ± 9 years, 62% men) scheduled for RCHOP, with LVEF50%, were evaluated at baseline, after third cycle and chemotherapy completion for 3D LVEF, 2D myocardial deformation (longitudinal, radial, circumferential strain - LS, RS, CS) and myocardial work (global constructive work, waste work, work index and work efficiency - GCW, GWW, GWI, GWE). NT-pro-BNP and troponin I were determined.After chemotherapy ended, 37 patients (28%) (group I) developed asymptomatic cardiotoxicity (8 mild form, 25 moderate form, 4 severe form); 93 patients (group II) did not. After third cycle, all patients had decreased LS, CS, RS, GCW, GWI, GWE and increased GWW, persistent after chemotherapy completion, with significant changes in group I. After third cycle, GWE and GCW were the best independent predictors for LVEF reduction; GWE decrease with5% after third cycle predicted cardiotoxicity after chemotherapy completed (91% sensitivity, 94% specificity).In NHL, myocardial work can diagnose subclinical cardiotoxicity and predict LVEF decline. These parameters should be used for sensitive evaluation of myocardial function during chemotherapy.

Aim: Left atrium (LA) assessment has gained significant interest in recent years because of its diagnostic and prognostic role in cardiovascular diseases. We aimed to assess the feasibility and reproducibility of three-dimensional echocardiography (3DE) versus two-dimensional echocardiography (2DE) for LA volumes (LAV) when measurements were performed by users with different levels of expertise in 3DE. Method:We prospectively recruited 35 consecutive patients referred to our echocardiography laboratory. Subjects underwent two separate 2DE and 3DE acquisitions of the LA in the same day by different users. Left atrial volumes were measured by the two users, who had similar levels of training in 2DE but different levels of training in 3DE – one advanced user and one beginner user. Results: Our results showed a good intra-observer reproducibility for 2DE (r=0.98) and an equally good reproducibility for 3DE LAVs when measured by the beginner user (r=0.97). Similarly, there was a good inter-observer reproducibility for the 2DE LAVs when measured by observers with similar levels of expertise in 2DE (r=0.98). However, similarly reproducible results were obtained for the 3DE LAVs when measured by users with significantly different levels of training in 3DE (r=0.98). Furthermore, there was a lower, yet acceptable (r>0.8), reproducibility for the 2DE LAVs when measured on separately acquired datasets by users who acquired the respective datasets, both with advanced level of training in 2DE. However, reproducibility was superior for 3DE LAVs when measured by the beginner and advanced users in 3DE (r=0.97). Conclusion: We conclude that 3DE is a technique that promises to improve patients’ overall assessment, showing a good feasibility and better reproducibility than 2DE for the measurement of LAVs, regardless of level of training in the method.

Left ventricular non-compaction (LVNC) with preserved ejection fraction (EF) is still a controverted entity. We aimed to characterize structural and functional changes in LVNC with heart failure with preserved EF (HFpEF). Methods: We enrolled 21 patients with LVNC and HFpEF and 21 HFpEF controls. For all patients, we performed CMR, speckle tracking echocardiography (STE), and biomarker assessment for HFpEF (NT-proBNP), for myocardial fibrosis (Galectin-3), and for endothelial dysfunction [ADAMTS13, von Willebrand factor, and their ratio]. By CMR, we assessed native T1 and extracellular volume (ECV) for each LV level (basal, mid, and apical). By STE, we assessed longitudinal strain (LS), globally and at each LV level, base-to-apex gradient, LS layer by layer, from epicardium to endocardium, and transmural deformation gradient. Results: In the LVNC group, mean NC/C ratio was 2.9 ± 0.4 and the percentage of NC myocardium mass was 24.4 ± 8.7%. LVNC patients, by comparison with controls, had higher apical native T1 (1061 ± 72 vs. 1008 ± 40 ms), diffusely increased ECV (27.2 ± 2.9 vs. 24.4 ± 2.5%), with higher values at the apical level (29.6 ± 3.8 vs. 25.2 ± 2.8%) (all p < 0.01); they had a lower LS only at the apical level (−21.4 ± 4.4 vs. −24.3 ± 3.2%), with decreased base-to-apex gradient (3.8 ± 4.7 vs. 6.9 ± 3.4%) and transmural deformation gradient (3.9 ± 0.8 vs. 4.8 ± 1.0%). LVNC patients had higher NT-proBNP [237 (156–489) vs. 156 (139–257) pg/mL] and Galectin-3 [7.3 (6.0–11.5) vs. 5.6 (4.8–8.3) ng/mL], and lower ADAMTS13 (767.3 ± 335.5 vs. 962.3 ± 253.7 ng/mL) and ADAMTS13/vWF ratio (all p < 0.05). Conclusion: LVNC patients with HFpEF have diffuse fibrosis, which is more extensive at the apical level, explaining the decrease in apical deformation and overexpression of Galectin-3. Lower transmural and base-to-apex deformation gradients underpin the sequence of myocardial maturation failure. Endothelial dysfunction, expressed by the lower ADAMTS13 and ADAMTS13/vWF ratio, may play an important role in the mechanism of HFpEF in patients with LVNC.

Aims None of the conventional echocardiographic parameters alone predict increased NTproBNP level and symptoms, making diagnosis of heart failure with preserved ejection fraction (HFpEF) very difficult in some cases, in resting condition. We evaluated LA functions by 2D speckle tracking echocardiography (STE) on top of conventional parameters in HFpEF and preHF patients with diastolic dysfunction (DD), in order to establish the added value of the LA deformation parameters in the diagnosis of HFpEF. Methods We prospectively enrolled 125 patients, 88 with HFpEF (68±9 yrs), and 37 asymptomatic with similar risk factors with DD (preHF) (61±8 yrs). We evaluated them by NTproBNP, conventional DD parameters, and STE. Global longitudinal strain (GS) was added. LA reservoir (R), conduit (C), and pump function (CT) were assessed both by volumetric and STE. 2 reservoir strain (S) derived indices were also measured, stiffness (SI) and distensibility index (DI). Results LA R and CT functions were significantly reduced in HFpEF compared to preHF group (all p2 = 0.506, p Conclusions By adding LA functional analysis, we might improve the HFpEF diagnosis accuracy, compared to present guidelines. LA pump function is the only one able to differentiates preHF from HFpEF patients at rest. A value of SR_CT < -1.66/s outperformed conventional parameters from the scoring system, reservoir strain, and LA overload indices in HFpEF diagnosis. We suggest that LA function by STE could be incorporated in the current protocol for HFpEF diagnosis at rest as a major functional criterion, in order to improve diagnostic algorithm, and also in the follow-up of patients with risk factors and DD, as a prognostic marker. Future studies are needed to validate our findings.

Left ventricular volumes (LVVs) and ejection fraction (LVEF) are key elements in the evaluation and follow-up of patients with heart failure with reduced ejection fraction (HFrEF). Therefore, a feasible and reproducible imaging method to be used by both experienced and in-training echocardiographers is mandatory. Our aim was to establish if, in a large echo lab, echocardiographers in-training provide feasible and more reproducible results for the evaluation of patients with HFrEF when using 3-dimensional echocardiography (3-DE) versus 2-dimensional echocardiography (2-DE). Sixty patients with HFrEF (46 males, age: 58 ± 17 y) underwent standard transthoracic 2-D acquisitions and 3-D multibeat full volumes of the left ventricle. One expert user in echocardiography (expert) and three echocardiographers with different levels of training in 2-DE (beginner, medium and advanced) measured the 2-D LVVs and LVEFs on the same consecutive images of patients with HFrEF. Afterward, the expert performed a 1-mo training in 3-DE analysis of the users, and both the expert and trainees measured the 3-D LVVs and LVEF of the same patients. Measurements provided by the expert and all trainees in echo were compared. Six patients were excluded from the study because of poor image quality. The mean end-diastolic LVV of the remaining 54 patients was 214 ± 75 mL with 2-DE and 233 ± 77 mL with 3-DE. Mean LVEF was 35 ± 10% with 2-DE and 33 ± 10% with 3-DE. Our analysis revealed that, compared with the expert user, the trainees had acceptable reproducibility for the 2-DE measurements, according to their level of expertise in 2-DE (intra-class coefficients [ICCs] ranging from 0.75 to 0.94). However, after the short training in 3-DE, they provided feasible and more reproducible measurements of the 3-D LVVs and LVEF (ICCs ranging from 0.89-0.97) than they had with 2-DE. 3-DE is a feasible, rapidly learned and more reproducible method for the assessment of LVVs and LVEF than 2-DE, regardless of the basic level of expertise in 2-DE of the trainees in echocardiography. In echo labs with a wide range of staff experience, 3-DE might be a more accurate method for the follow-up of patients with HFrEF.

Background In patients with heart failure with reduced ejection fraction (HFrEF), right ventricular (RV) size and dysfunction by 2-dimensional echocardiography (2DE) were identified as risk factors for mortality and morbidity, but 3-dimensional echocardiography (3DE) enabled itself as a more reproducible and accurate method. Aim To assess the comparative prognostic value of parameters of RV size and dysfunction, measured by 2DE and 3DE, in patients with ischemic and non-ischemic HFrEF, on optimal clinical care, at long-term follow-up. Methods 142 consecutive patients (62±12 yrs, 104 males) with HFrEF, in sinus rhythm, were assessed by 2DE and 3DE, including RV full-volume acquisitions. RV diameter (RVd), RV end-systolic (RV_EDA) and end-diastolic areas (RV_ESA), RV fractional area change (RVFAC), and 2D_TAPSE were measured by 2DE. RV end-diastolic (RV_EDV) and end-systolic volumes (RV_ESV), RV ejection fraction (RV_EF), and 3D_TAPSE were measured by a dedicated 3DE software. Patients were followed for 37±16 months after the index event. Primary outcome was cardiac death (CD). Secondary outcomes were: 1) HF hospitalizations (HFH); 2) a composite cardiac events (CE) end-point of CD or HFH, myocardial infarction, coronary revascularization, arrhythmias, or CRT. Results 38 CD, 47 HFH, and 62 CE occurred during follow-up. Mean RVd was 34±7 mm, RV_EDA 20±11 cm2, RV_ESA 12±5 cm2, RV_FAC 37±13%, RV_EDV 84±25 ml/m2, RV_ESV 52±22 ml/m2, and RV_EF 39±10%. Mean 2D_TAPSE was 18±4 mm, while mean 3D_TAPSE was 16±4 mm. By 2DE, only RV_ESA and RV_FAC, but not RV_EDA or RVd, correlated with CD, HFH, and CE. 2D_TAPSE correlated with HFH, but not with CD or CE, while 3D_TAPSE correlated with all primary and secondary outcomes. By 3DE, RV_ESV, but not RV_EDV, correlated with CD, HFH, and CE. Moreover, 3D RV_EF had better correlations with primary and secondary outcomes than 2D RV_FAC (z=3.8, z=2.5, and z=2.5, all p Conclusion In patients with ischemic and non-ischemic HFrEF, 3DE parameters of RV size and dysfunction are better predictors for death and re-hospitalization than 2DE parameters. The RV_EF measured by 3DE was the best predictor for death in patients with HFrEF. Funding Acknowledgement Type of funding source: None

Introduction and Objectives. Patients with dilated cardiomyopathy (DCM) and functional mitral regurgitation (FMR) present altered geometry and dynamics of the mitral annulus (MA). We aimed to further assess the relationship between the MA dysfunction, FMR severity, and LA dysfunction in patients with ischemic and nonischemic DCM by using three-dimensional transthoracic echocardiography (3DTTE). Methods. 56 patients (58 ± 17 years, 42 men) with DCM and FMR and 52 controls, prospectively enrolled, underwent 3DTTE dedicated for mitral valve (MV), LA, and left ventricle (LV) quantitative analysis. Results. Patients with FMR vs. controls presented increased MA size and sphericity during the entire systole, whereas MA fractional area change (MAFAC) and MA displacement were decreased (15 ± 5 vs. 28 ± 5%; and 5 ± 3 vs. 10 ± 2 mm, p<0.001). In patients with moderate/severe FMR, MA diameters correlated with PISA radius, EROA, and regurgitant volume (Rvol), as also did the MA area (with PISA radius, EROA, and Rvol: r = 0.48, r = 0.58, and r = 0.47, p<0.05). MAFAC correlated inversely with EROA and Rvol (r = −0.32 and r = −0.35, p<0.05), with both active and total LA emptying fractions and with LV ejection fraction as well. In a stepwise multivariate regression model, decreased MAFAC and increased LA volume independently predicted patients with severe FMR. Conclusions. Patients with DCM and FMR have MA geometry remodeling and contractile dysfunction, correlated with the severity of FMR. MA contractile dysfunction correlated with both LA and left LV pumps dysfunctions and predicted patients with severe FMR. Our results provide new insights that might help with better selection of patients for MV transcatheter procedures.

International audience; Two methods are currently available for left atrial (LA) strain measurement by speckle tracking echocardiography, with two different reference timings for starting the analysis: QRS (QRS-LASr) and P wave (P-LASr). The aim of MASCOT HIT study was to define which of the two was more reproducible, more feasible, and less time consuming. In 26 expert centers, LA strain was analyzed by two different echocardiographers (young vs senior) in a blinded fashion. The study population included: healthy subjects, patients with arterial hypertension or aortic stenosis (LA pressure overload, group 2) and patients with mitral regurgitation or heart failure (LA volume–pressure overload, group 3). Difference between the inter-correlation coefficient (ICC) by the two echocardiographers using the two techniques, feasibility and analysis time of both methods were analyzed. A total of 938 subjects were included: 309 controls, 333 patients in group 2, and 296 patients in group 3. The ICC was comparable between QRS-LASr (0.93) and P-LASr (0.90). The young echocardiographers calculated QRS-LASr in 90% of cases, the expert ones in 95%. The feasibility of P-LASr was 85% by young echocardiographers and 88% by senior ones. QRS-LASr young median time was 110 s (interquartile range, IR, 78-149) vs senior 110 s (IR 78-155); for P-LASr, 120 s (IR 80-165) and 120 s (IR 90-161), respectively. LA strain was feasible in the majority of patients with similar reproducibility for both methods. QRS complex guaranteed a slightly higher feasibility and a lower time wasting compared to the use of P wave as the reference.

Background Left ventricular (LV) deformation is dependent on mechanical load and does not reflect directly the myocardial energy consumption. Thus, measurement of global and regional myocardial work might be alternative and complementary methods for the assessment of myocardial function. However, there is no data regarding myocardial work changes during the heart failure continuum, from normal to diastolic dysfunction (DD), and to heart failure with preserved ejection fraction (HFpEF). Methods We assessed 80 subjects by 2D conventional and speckle tracking echocardiography (2DSTE): 25 patients with DD, 30 with HFpEF, and 25 normal, control subjects. We measured NTproBNP, LV ejection fraction (EF), and E/E' ratio. We used a new approach to calculate myocardial work, during mechanical systole and isovolumetric relaxation, by 2DSTE: global constructive work (GCW), as the “positive” work of the heart; global wasted work (GWW), as the “negative” work of the heart; global work efficiency (GWE), as the GCW/(GCW + GWW) in %; and global work index (GWI), as the GCW added to GWW. Similarly, a regional, segmental analysis was performed (18 segments model) (Figure 1). Results GCW increases in patients with DD, probably as a compensatory mechanism to preserve LV function against an increased after load, and decreases back to the normal values in HFpEF, while GWE significantly decreases from normal subjects to patients with DD, and then further in patients with HFpEF (table). Meanwhile, GWW increases from normal subjects to patients with DD, and then further in patients with HFpEF. As expected, GWI does not change significantly. By segmental analysis, first segment affected in terms of myocardial work is basal antero-septal segment, with low WE and higher WW (figure), probably due to the flat shape (based on the Laplace law), with a compensatory increased CW in the apical segments. NTproBNP level and E/E' ratio correlated only with GWW (r=0.4, p=0.013). Comparative global myocardial work Group LVEF (%) E/E' NTproBNP (pg/ml) GWI (mmHg%) GWE (%) GCW (mmHg%) GWW (mmHg%) Controls 58±6 7.3±2.4 – 2102±303 95.5±1.8 2295±279 87.9±39.6 DD 57±8 7.7±2.4 36±25 2296±431 94.8±2.3 2550±463 108±50 HFpEF 63±7 10.3±3.1 349±418 2074±485 93.5±2.5 2300±535 125±51 P (Anova) 0.004 Figure 1. Myocardial Work Conclusion Myocardial work efficiency decreases and wasted work increases in parallel with the severity of LV dysfunction. The first myocardial segment affected is basal antero-septal. Therefore, new parameters of myocardial work, derived from 2DSTE, might provide a better assessment of LV function in patients with DD or HFpEF. Acknowledgement/Funding This work was supported by a grant of Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1-TE-2016-0669, within PNCDI III

Background 2D speckle tracking echocardiography (2DSTE) was proved to be accurate for the assessment of the RV function. However, normal values for RV strain refer mostly to 3- or 6-segment models, excluding the contribution of other RV walls to RV function. We analyze RV function by 2DSTE in a normal population, using parasternal two-(2C) and apical four-chamber (4C) RV views, and creating a new 12-segment model for a potential better definition of RV function. Methods We prospectively evaluated 100 normals using 2DE and STE. We assessed the RV systolic function from regional strain (basal, mid, and apical), and at the level of each wall: lateral (LS), septal (SS), inferior (IS), and anterior (AS), and also global strain for 4C (4CGS), and 2C (2CGS). Global systolic strain rate (SRs) was measured from 2C and 4C views. Diastolic function was assessed from early (SRe) and late global strain rate (SRl), for both views. Results A total of 70 healthy individuals (48±15 years, 34 men) were suitable for concomitant 4C and 2CRV analysis. Feasibility of the STE analysis was 87.8%. We found significantly lower SS by comparison with LS, AS, and IS (P

Background: Transcatheter mitral valve replacement (TMVR) is a new therapeutic option for high surgical risk patients with mitral regurgitation (MR). Mitral valve (MV) geometry quantification is of paramount importance for success of the procedure and transthoracic 3D echocardiography represents a useful screening tool. Accordingly, we sought to asses MV geometry in patients with functional MR (FMR) that would potentially benefit of TMVR, focusing on the comparison of mitral annulus (MA) geometry between patients with ischemic (IMR) and non ischemic mitral regurgitation (nIMR). Methods: We retrospectively selected 94 patients with severe FMR: 41 (43,6%) with IMR and 53 (56,4%) with nIMR. 3D MA analysis was performed on dedicated transthoracic 3D data sets using a new, commercially-available software package in two moments of the cardiac cycle (early-diastole and mid-systole). We measured MA dimension and geometry parameters, left atrial and left ventricular volumes. Results: Maximum (MA area 10.7 ± 2.5 cm 2 vs 11.6 ± 2.7 cm 2 , p > 0.05) and the best fit plane MA area (9.9 ± 2.3 cm 2 vs 10.7 ± 2.5 cm 2 , p > 0.05, respectively) were similar between IMR and nIMR. nIMR patients showed larger mid-systolic 3D area (9.8 ± 2.3 cm 2 vs 10.8 ± 2.7 cm 2 , p < 0.05) and perimeter (11.2 ± 1.3 cm vs 11.8 ± 1.5 cm, p < 0.05) with longer and larger leaflets, and wider aorto-mitral angle (135 ± 10° vs 141 ± 11°, p < 0.05). Conversely, the area of MA at the best fit plane did not differ between IMR and nIMR patients (9 ± 1.1 cm 2 vs 9.9 ± 1.5 cm 2 , p > 0.05). Conclusions: Patients with ischemic and non-ischemic etiology of FMR have similar maximum dimension, yet systolic differences between the two groups should be taken into account to tailor prosthesis's selection. Trial registration: N.A.

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.

Growth hormone deficiency (GHD) in adults is associated with increased cardiovascular events, but detailed assessment of cardiac and vascular function is lacking. Thus we assessed cardiac, arterial, and endothelial functions, using conventional and speckle-tracking echocardiography, in adults with GHD compared with controls with similar cardiovascular risk.Fifty-two patients with GHD (47 ± 16 years; 34 men) and no cardiovascular disease or diabetes were enrolled prospectively and compared with 50 age- and sex-matched controls. Comprehensive echocardiography was performed in all participants. Regional left ventricular (LV) function was assessed from global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS), whereas LV torsion (LVtor) was calculated from basal (RotB) and apical (RotA) rotations. Arterial function was assessed from intima-media thickening, local wave speed, and beta index of stiffness, whereas endothelial function was assessed from flow-mediated dilation. Levels of pro-brain natriuretic peptide (proBNP) were measured.GLS and GCS were decreased more in patients with GHD than in controls (-17.2% ± 2.7% vs. -19.3% ± 3.3% and -15.9% ± 5.4% vs. -18.8% ± 3.5%; both P0.01), whereas GRS was similar. RotB and LVtor were also decreased in patients with GHD (-4.8° ± 2.6° vs. -6.2° ± 2.1°/cm and 1.8° ± 0.6° vs. 2.3° ± 1.1°/cm; both P0.05). ProBNP was increased in patients with GHD (61.0 ± 74 pg/dL vs. 24.7 ± 21 pg/dL; P = 0.002). Arterial and endothelial functions were similar between groups.In conclusion, adults with GHD had LV longitudinal dysfunction and increased proBNP levels compared with controls, suggesting intrinsic myocardial disease. Further studies are needed to assess if this cardiac impairment in adults with GHD is reversible after GH replacement.

Multiple sclerosis (MS), neurologic disease affecting young population, may cause cardiovascular dysfunction, due to autonomous nervous dysfunction, physical invalidity, increased oxidative stress, and systemic inflammatory status. However, cardiovascular function is rarely evaluated in these patients. We assessed left and right ventricular (LV and RV) function by 2D, 3D, tissue Doppler, and speckle tracking echocardiography, and vascular function by remodeling, stiffness, and endothelial dysfunction parameters in patients with MS, compared to control subjects. 103 subjects (35 ± 10 years,70 women) were studied: 67 patients with MS and 36 control subjects. Patients with MS had decreased LV systolic function, confirmed by lower 2D and 3D ejection fraction, mitral annular plane systolic excursion, longitudinal myocardial systolic velocities, and 2D and 3D global longitudinal strain. The RV function was also decreased, as demonstrated by lower fractional area change, tricuspid annular plane systolic excursion, longitudinal systolic velocities, and longitudinal strain. Additionally, LV diastolic and left atrial (LA) function were decreased compared to controls. The parameters of arterial and endothelial function were similar between groups. Patients with MS have impaired biventricular function by comparison with normal subjects, with reduced LA function, but normal arterial and endothelial function. The noninvasive echocardiographic techniques might help to determine patients with MS at risk of developing cardiovascular dysfunction.

Multiple sclerosis (MS) is a chronic neurological condition, characterized by recurrent episodes of inflammation and demyelination of the central nervous system called relapsing-remitting episodes, and continuous axonal degeneration that leads to irreversible progressive invalidity. Patients with multiple sclerosis present a higher mortality rate compared to the general population, and the excess of mortality may be explained by the increased cardiovascular risk and occurrence of cardiovascular disease. However, the exact pathways to cardiovascular dysfunction are not yet completely elucidated. This review focuses on the most important mechanisms of cardiovascular dysfunction in MS, such as the cardiomyocite structure alteration, the cardiovascular autonomous nervous system dysfunction, physical invalidity, oxidative stress and endothelial dysfunction, as well as the impact of cardiovascular risk factors in MS. The latest evidence about therapeutic approaches for MS, such as immunomodulatory treatment, vitamin D supplementation and statins are also discussed. There is little knowledge about the cardiovascular dysfunction in MS, and further research is required to improve the understanding of these complex mechanisms.

Left atrial (LA) strain and strain rate, determined by speckle-tracking echocardiography (STE), are reproducible indices to assess LA function. Different normal ranges for LA phasic functions have been reported. We investigated the role of the reference point (P- and R-wave), gain, and region of interest (ROI), as the major sources of variation when assessing LA function. 52 subjects were evaluated for LA conventional and STE analysis. 45 of them (46 ± 14 years, 26 men) were feasible for concomitant LA deformation, and LA phasic volumes and ejection fractions (LAEF) evaluation. First, we compared the P- and R-wave methods, for the evaluation of the LA functions. We used diastolic mitral profile to clearly delineate the time intervals for each LA function. For the P-wave method, active function was assessed from negative global strain as a difference between the strain at pre-atrial contraction and strain just before mitral valve closure (GSA-), and late diastolic strain rate (GSRL); passive function from positive strain at MVO (GSA+), and from early negative diastolic strain rate (GSRE); reservoir function from the sum of GSA− and GSA+ (TGSA), and positive strain rate at the beginning of LV systole (GSR+). For the R-wave method we used the same SR parameters. The active function was evaluated by late positive global strain (GSAC), the reservoir by positive peak before the opening of the mitral valve (TGSA), and conduit function by the difference between TGSA and GSAC (GSA+). Then, by using P-wave method, we measured all previously described parameters for different gains—minimum (G0), medium (G12), and maximum (G24), and for different ROIs—minimum (ROI0), step 1 (ROI1), and 2 (ROI2). Feasibility of the LA strain measurements was 87 %. Active LA function was similar in the absolute value (GSAC and GSA−), whereas passive and reservoir functions were significantly higher (GSA+, TGSA) with the R-wave method. Active LAEF correlated with GSA− measured by the P-wave (r = −0.44, p = 0.002), but not with the GSAC measured by the R-wave method. Similar correlations were found for passive and reservoir LAEF with correspondent strain parameters, only with P-wave method. There were no differences between methods regarding SR indices and their correlations with correspondent LAEFs. Increase of gain from minimum to maximum overestimated all measured LA functions (all p < 0.05). Intermediary changes did not have a significant impact on the measurement of active and conduit function, but they do have on the measurement of the reservoir function. Increase of ROI from minimum to ROI2 was associated with an overestimation of all measurements of atrial functions (all p < 0.05). For all parameters, except GSR+, a decrease of atrial S and SR values from minimum ROI to step 1 was recorded. For GSA+, TGSA, GSRE a decrease of S and SR values with each ROI step was recorded. The two methods used to assess LA functions by STE do not provide similar results. The R-wave method essentially ignores negative peak, creating a positive strain for atrial contraction, and also provides higher values for the reservoir and conduit functions, by comparison with the P-wave method. Increase of gain overestimates, whereas increase of ROI underestimates all parameters of LA functions. Therefore, we suggest that P-wave as a reference point, a medium gain, and a minimum ROI should be used as the best choice for a correct assessment.

Resumen Introduccion y objetivos La ecocardiografia con speckle tracking bidimensional es un nuevo instrumento para evaluar la funcion del miocardio. El objetivo de este estudio fue evaluar los parametros de rotacion y strain del ventriculo izquierdo mediante la ecocardiografia con speckle tracking bidimensional en un gran grupo de adultos sanos de una amplia gama de edades, con objeto de establecer los valores de referencia de dichos parametros y determinar la influencia de la edad, el sexo y los factores hemodinamicos. Metodos Se realizaron ecocardiografias transtoracicas a 247 voluntarios sanos (139 mujeres; media de edad, 44 ± 16 [intervalo, 18-80] anos). Efectuamos determinaciones de los valores de strain sistolico maximo longitudinal, circunferencial y radial, asi como de la rotacion y el giro del ventriculo izquierdo. Resultados Los valores medios de strain total longitudinal, radial y circunferencial fueron –21,5% ± 2,0%, 40,1 ± 11,8% y –22,2 ± 3,4%, respectivamente. El strain longitudinal fue significativamente mas negativo en las mujeres, mientras que el strain radial y el circunferencial y los parametros rotacionales fueron similares en ambos sexos. En consecuencia, los limites inferiores de la normalidad para los componentes del strain fueron –16,9% en los varones y –18,5% en las mujeres para el strain longitudinal, –15,4% para el strain circunferencial y 24,6% para el strain radial, con independencia del sexo. Los valores de strain longitudinal fueron mas negativos en la base que en los segmentos apicales. Los valores medios de la rotacion fueron–6,9 ± 3,5 ° en la base, 13,0 ± 6,5° para la rotacion apical y 20,0 ± 7,3° para el giro neto. Conclusiones Presentamos una evaluacion detallada de la deformacion normal del miocardio y la mecanica rotacional en una cohorte amplia de voluntarios sanos. Observamos que las mujeres presentan un strain longitudinal mas negativo, lo cual explica su mayor fraccion de eyeccion del ventriculo izquierdo. La disponibilidad de valores de referencia de esos parametros puede facilitar su aplicacion en la practica clinica habitual.

Introduction and objectives Two-dimensional speckle-tracking echocardiography is a novel tool to assess myocardial function. The purpose of this study was to evaluate left ventricular myocardial strain and rotation parameters by two-dimensional speckle-tracking echocardiography in a large group of healthy adults across a wide age range to establish their reference values and to assess the influence of age, sex, and hemodynamic factors. Methods Transthoracic echocardiograms were acquired in 247 healthy volunteers (139 women, 44 years [standard deviation, 16 years old] (range, 18-80 years). We measured longitudinal, circumferential, and radial peak systolic strain values, and left ventricular rotation and twist. Results Average values of global longitudinal, radial, and circumferential strain were -21.5% (standard deviation, 2.0%), 40.1% (standard deviation, 11.8%) and -22.2% (standard deviation, 3.4%), respectively. Longitudinal strain was significantly more negative in women, whereas radial and circumferential strain and rotational parameters were similar in both sexes. Accordingly, lower limits of normality for the strain components were -16.9% in men and -18.5% in women for longitudinal strain, and -15.4% for circumferential and 24.6% for radial strain, irrespective of sex. Longitudinal strain values were more negative at the base than at apical segments. Mean rotational values were -6.9 ° (standard deviation, 3.5 °) for the base, 13.0 ° (standard deviation, 6.5 °) for apical rotation, and 20.0 ° (standard deviation, 7.3 °) for net twist. Conclusions We report the comprehensive assessment of normal myocardial deformation and rotational mechanics in a large cohort of healthy volunteers. We found that women have more negative longitudinal strain, accounting for their higher left ventricular ejection fraction. Availability of reference values for these parameters may foster their implementation in the clinical routine. Full English text available from: www.revespcardiol.org/en. © 2013 Sociedad Española de Cardiología. Published by Elsevier España, S.L. All rights reserved.

Tricuspid valve (TV) anatomy and function play an important prognostic role in several heart diseases and in the development of functional tricuspid regurgitation. According to current guidelines for management of heart valve disease, the tricuspid annulus (TA) diameter measured by 2-dimensional

Background— Our study sought to (1) identify reference values for left atrial (LA) volumes and phasic function indices by 3-dimensional echocardiography (3DE) and compare them with those measured by 2-dimensional echocardiography (2DE) and (2) analyze their relationship with age, sex, body size, and left ventricular function. Accuracy and reproducibility of 3DE and 2DE have been also tested to evaluate the robustness of our data. Methods and Results— We obtained maximal, minimal, and preA LA volumes by 3DE and 2DE in 276 healthy volunteers (18–79 years; 57% women). Limits of normality for LA volumes and total LA emptying fraction were larger with 3DE than with 2DE (maximal LA volume: 43 versus 35 mL/m 2 ; preA LA volume: 31 versus 25 mL/m 2 ; minimal LA volume: 18 versus 14 mL/m 2 ; 53 versus 48%, respectively; P Conclusions— This study provides reference values for LA 3DE volumes and function from a relatively large cohort of healthy subjects with a wide age range. Our data may help clinicians to identify LA remodeling and dysfunction.

Background Left atrial (LA) longitudinal strain (LS) using two-dimensional speckle-tracking echocardiography has emerged as an important diagnostic and prognostic parameter in various cardiovascular conditions. However, its reference values, their correlations with demographics characteristics, and its physiologic determinants remain to be established. Methods Accordingly, 171 healthy volunteers (mean age, 45 ± 12 years; 61% women) in whom LS was obtained from both apical four- and two-chamber dedicated views of the left atrium, considering the P-P interval on the electrocardiogram as the reference cardiac cycle, were prospectively studied. From the LA LS curve we measured the extent of the negative deflection (LSneg), representing LA active contraction, the positive deflection (LSpos) during LA filling, and total LS (LStot), as the sum of LSneg and LSpos values. Results Average values for biplane LA LSpos, LSneg, and LStot were 19.7%, −14.5%, and 33.3%, respectively. On multivariate analysis, age, left ventricular (LV) global LS and volume, and LV diastolic function were the main physiologic determinants of LA LSpos ( R 2 = 0.57) and LStot ( R 2 = 0.40), whereas systolic blood pressure, E/A ratio, global LS, and LV stroke volume were the main determinants of LA LSneg ( R 2 = 0.20). Women had higher LSpos and LStot than men, particularly before 50 years of age. LA LSpos and LStot decreased with aging, with different trends in men and women. Conclusions LA LS values are different in men and women and should be interpreted taking into account patient age and LV function as well. These reference values may help identify subclinical LA dysfunction in several cardiovascular or systemic conditions.

Background Intervendor consistency of left ventricular (LV) volume measurements using three-dimensional transthoracic echocardiography (3DTTE) has never been reported. Accordingly, we designed a prospective study to (1) compare head-to-head the accuracy of three three-dimensional echocardiography (3DE) systems in measuring LV volumes and ejection fraction (EF) against cardiac magnetic resonance (CMR); (2) assess the intervendor variability of LV volumes and EF; and (3) compare the accuracy of fully automated versus semiautomated (i.e., manually corrected) methods of LV endocardial delineation against CMR. Methods We studied 92 patients (64% males, 52 years [95% CI, 20-83]) with a wide range of end-diastolic volumes (from 87 to 446 mL) and EFs (from 16% to 77%) using three different 3DE platforms (iE33; Vivid E9; Acuson SC2000) during the same echo study. CMR was performed within 3 ± 5 hours from the 3DE study in 35 patients. Results LV volumes provided by the three 3DE systems correlated with CMR volumes: end-diastolic volume (iE33: R 2 = 0.93; E9: R 2 = 0.94; SC2000: R 2 = 0.94), end-systolic volume (iE33: R 2 = 0.93; E9: R 2 = 0.95; SC2000: R 2 = 0.94), and EF (iE33: R 2 = 0.79; E9: R 2 = 0.80; SC2000: R 2 = 0.77). In the 92 patients studied, LV volumes and EFs measured with the three systems were similar. Use of fully automated endocardial border detection algorithms significantly underestimated LV volumes, and the degree of underestimation was higher with larger LV volumes. Conclusions LV volumes and EFs measured with the three 3DE systems are consistent. Fully automated algorithms underestimated LV volumes. Our findings may help in the clinical interpretation of LV parameters obtained using different 3DE systems and encourage the clinical use of 3DTTE.