Myocardial work-A new tool for early detection of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy induced-cardiotoxicity in hematological patients.

BACKGROUND: Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (RCHOP) chemotherapy in non-Hodgkin's lymphoma (NHL) has risk of cardiotoxicity. PURPOSE: To determine the role of myocardial work and biomarkers in subclinical diagnosis and prediction of cardiotoxicity. METHODS: The 130 NHL patients (52 ± 9 years, 62% men) scheduled for RCHOP, with LVEF>50%, 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. RESULTS: 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 with>5% after third cycle predicted cardiotoxicity after chemotherapy completed (91% sensitivity, 94% specificity). CONCLUSIONS: 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.

Comparison of mitral annulus geometry between patients with ischemic and non-ischemic functional mitral regurgitation: implications for transcatheter mitral valve implantation.

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 cm2 vs 11.6 ± 2.7 cm2, p > 0.05) and the best fit plane MA area (9.9 ± 2.3 cm2 vs 10.7 ± 2.5 cm2, p > 0.05, respectively) were similar between IMR and nIMR. nIMR patients showed larger mid-systolic 3D area (9.8 ± 2.3 cm2 vs 10.8 ± 2.7 cm2, 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 cm2 vs 9.9 ± 1.5 cm2, 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.

Sources of variation in assessing left atrial functions by 2D speckle-tracking echocardiography.

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.

A new comprehensive 12-segment approach to right ventricular systolic and diastolic functions by 2D speckle tracking echocardiography in healthy individuals.

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<.001). All S/SR parameters (GS, SRs, and SRe) were higher in 2C view than in 4C view (P<.001). All systolic S/SR parameters did not change with age. The early diastolic SR decreased, while the late diastolic SR increased with age. CONCLUSION: Our 12-segment RV strain model is feasible. Moreover, 2DSTE analysis using 2C and 4C views of the RV does not provide similar information. Rather, they offer complementary data. This might be of particularly clinical interest in diseases with regional RV dysfunction.

Right Atrial Remodeling and Outcome in Patients with Secondary Tricuspid Regurgitation.

BACKGROUND: In patients with secondary tricuspid regurgitation (STR), right atrial remodeling (RAR) is a proven marker of disease progression. However, the prognostic value of RAR, assessed by indexed right atrial volume (RAVi) and reservoir strain (RAS), remains to be clarified. Accordingly, the aim of our study is to investigate the association with outcome of RAR in patients with STR. METHODS: We enrolled 397 patients (44% men, 72.7 ± 13 years old) with mild to severe STR. Complete two-dimensional and speckle-tracking echocardiography analysis of right atrial and right ventricular (RV) size and function were obtained in all patients. The primary end point was the composite of death from any cause and heart failure hospitalization. RESULTS: After a median follow-up of 15 months (interquartile range, 6-23), the end point was reached by 158 patients (39%). Patients with RAS <13% and RAVi >48 mL/m2 had significantly lower survival rates compared to patients with RAS ≥13% and RAVi ≤48 mL/m2 (log-rank P < .001). On multivariable analysis, RAS <13% (hazard ratio, 2.11; 95% CI, 1.43-3.11; P < .001) and RAVi > 48 mL/m2 (hazard ratio, 1.49; 95% CI, 1.01-2.18; P = .04) remained associated with the combined end point, even after adjusting for RV free-wall longitudinal strain, significant chronic kidney disease, and New York Heart Association class. Secondary tricuspid regurgitation excess mortality increased exponentially with values of 18.2% and 51.3 mL/m2 for RAS and RAVi, respectively. In nested models, the addition of RAS and RAVi provided incremental prognostic value over clinical, conventional echocardiographic parameters of RV size and function and RV free-wall longitudinal strain. CONCLUSIONS: In patients with STR, RAR was independently associated with mortality and heart failure hospitalization. Assessment of RAR could improve risk stratification of patients with STR, potentially identifying those who may benefit from optimization of medical therapy and a closer follow-up.

Clinical Impact of the Volumetric Quantification of Ventricular Secondary Mitral Regurgitation by Three-Dimensional Echocardiography.

BACKGROUND: The assessment of ventricular secondary mitral regurgitation (v-SMR) severity through effective regurgitant orifice area (EROA) and regurgitant volume (RegVol) calculations using the proximal isovelocity surface area (PISA) method and the two-dimensional echocardiography volumetric method (2DEVM) is prone to underestimation. Accordingly, we sought to investigate the accuracy of the three-dimensional echocardiography volumetric method (3DEVM) and its association with outcomes in v-SMR patients. METHODS: We included 229 patients (70 ± 13 years, 74% men) with v-SMR. We compared EROA and RegVol calculated by the 3DEVM, 2DEVM, and PISA methods. The end point was a composite of heart failure hospitalization and death for any cause. RESULTS: After a mean follow-up of 20 ±11 months, 98 patients (43%) reached the end point. Regurgitant volume and EROA calculated by 3DEVM were larger than those calculated by 2DEVM and PISA. Using receiver operating characteristic curve analysis, both EROA (area under the curve, 0.75; 95% CI, 0.68-0.81; P = .008) and RegVol (AUC, 0.75; 95% CI, 0.68-0.82; P = .02) measured by 3DEVM showed the highest association with the outcome at 2 years compared to PISA and 2DEVM (P < .05 for all). Kaplan-Meier analysis demonstrated a significantly higher rate of events in patients with EROA ≥ 0.3 cm2 (cumulative survival at 2 years: 28% ± 7% vs 32% ± 10% vs 30% ± 11%) and RegVol ≥ 45 mL (cumulative survival at 2 years: 21% ± 7% vs 24% ± 13% vs 22% ± 10%) by 3DEVM compared to those by PISA and 2DEVM, respectively. In Cox multivariable analysis, 3DEVM EROA remained independently associated with the end point (hazard ratio, 1.02, 95% CI, 1.00-1.05; P = .02). The model including EROA by 3DEVM provided significant incremental value to predict the combined end point compared to those using 2DEVM (net reclassification index = 0.51, P = .003; integrated discrimination index = 0.04, P = .014) and PISA (net reclassification index = 0.80, P < .001; integrated discrimination index = 0.06, P < .001). CONCLUSIONS: Effective regurgitant orifice area and RegVol calculated by 3DEVM were independently associated with the end point, improving the risk stratification of patients with v-SMR compared to the 2DEVM and PISA methods.

Cardiovascular Toxicity Induced by Vascular Endothelial Growth Factor Inhibitors.

Cardiotoxicity is an important side effect of vascular endothelial growth factor (VEGF) inhibitors therapy used in the treatment of various malignancies, leading to increased morbidity and mortality. Arterial hypertension, cardiac ischemia with the acceleration of atherosclerosis, arrhythmias, myocardial dysfunction and thromboembolic disease are the most feared cardiovascular adverse reactions due to VEGF inhibitors. Susceptibility for the occurrence of VEGF inhibitors-induced cardiotoxicity has multifactorial determinants, with a significant inter-individual variation. Baseline cardiovascular risk assessment of the patient, type and stage of cancer, dose and duration of VEGF inhibitors treatment and adjuvant chemotherapy or radiotherapy are the main predictors for cardiotoxicity. The role of the cardio-oncology team becomes essential for achieving maximum therapeutic anti-angiogenic effects with minimum cardiovascular side effects. This review will summarize the incidence, risk factors, mechanisms, management and treatment of VEGF inhibitors-induced cardiovascular toxicity.

Functional Regurgitation of Atrioventricular Valves and Atrial Fibrillation: An Elusive Pathophysiological Link Deserving Further Attention.

In patients with structurally normal atrioventricular valvular apparatus, functional regurgitation of the mitral or tricuspid valves has been attributed mainly to ventricular dilation and/or dysfunction, through a combination of annulus dilation and tethering of the valve leaflets. The occurrence of functional regurgitation of atrioventricular valves in patients with long-standing persistent atrial fibrillation and atrial dilation but normal ventricular size and function has received much less attention, and its peculiar mechanisms still remain to be understood. This distinct form of functional regurgitation (i.e., "atrial functional regurgitation") may require different treatment and interventional repair approaches than the classical functional regurgitation due to ventricular dilatation and dysfunction ("ventricular functional regurgitation"), and current guideline recommendations do not yet address this distinction. Clarifying the differences in the pathophysiology of atrial functional regurgitation and its management implications is of paramount importance. This review describes briefly the comparative anatomy of mitral and tricuspid apparatus and the pathophysiology and typical echocardiographic features of atrial functional regurgitation compared with ventricular functional regurgitation, as well as the added value of three-dimensional echocardiography as an essential imaging tool to clarify the mechanisms involved in its development.

Intervendor Consistency and Accuracy of Left Ventricular Volume Measurements Using Three-Dimensional Echocardiography.

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: R2 = 0.93; E9: R2 = 0.94; SC2000: R2 = 0.94), end-systolic volume (iE33: R2 = 0.93; E9: R2 = 0.95; SC2000: R2 = 0.94), and EF (iE33: R2 = 0.79; E9: R2 = 0.80; SC2000: R2 = 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.

Impaired Cardiac Function in Patients with Multiple Sclerosis by Comparison with Normal Subjects.

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.

Heart Failure with Mid-Range Ejection Fraction - a New Category of Heart Failure or Still a Gray Zone.

Heart failure with midrange ejection fraction (HFmrEF) is a new category of heart failure (HF), inbetween HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Previous studies were mainly conducted in HFrEF patients having a left ventricle ejection fraction (LVEF) lower than 35-40%. Later on, HFpEF captured the spot-light of the research field, and studies focused on patients with HF symptoms, but with a LVEF exceeding 50%. Consequently, a gap of knowledge comprising the LVEF between 40 and 49% has arisen. Current studies focusing on patients with HFmrEF are arguing the same conclusions or even having contradictory findings. HFmrEF has a prevalence of 10-20% of HF patients. HFmrEF has distinct, but intermediate clinical, structural and functional characteristics, as well as intermediate outcomes in comparison with HFrEF and HFpEF. However, there is still a large gap in evidence regarding detailed hemodynamic characteristics, long-term follow-up and optimal therapeutic options for these patients. Extensive research was recommended in order to improve knowledge about this "gray area" of patients with HF. Therefore, we aimed to provide an over-view of the existing and lacking data regarding patients with HFmrEF.

Left Atrial Volumes and Function by Three-Dimensional Echocardiography: Reference Values, Accuracy, Reproducibility, and Comparison With Two-Dimensional Echocardiographic Measurements.

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<0.001). 3DE LA volumes indexed by body surface area were similar in men and women and increased with age. On multivariable analysis, age, weight, and left ventricular systolic and diastolic function indices resulted as correlates of LA 3DE indices. LA volumes were tightly correlated with cardiac magnetic resonance measurements, yet more underestimated by 2DE versus 3DE (bias±SD: -17±16 versus -7±15 mL, respectively). Among all LA parameters, maximal LA volume and total emptying fraction were the most reproducible, including at test-retest and at expert versus trainee comparisons. 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.

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 (ß = 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.

Physiologic Determinants of Left Atrial Longitudinal Strain: A Two-Dimensional Speckle-Tracking and Three-Dimensional Echocardiographic Study in Healthy Volunteers.

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 (R2 = 0.57) and LStot (R2 = 0.40), whereas systolic blood pressure, E/A ratio, global LS, and LV stroke volume were the main determinants of LA LSneg (R2 = 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.

Dynamic changes in tricuspid annular diameter measurement in relation to the echocardiographic view and timing during the cardiac cycle.

BACKGROUND: Tricuspid annular (TA) size and function play important roles in planning the need for associated TA annuloplasty in patients undergoing cardiac surgery for left-sided heart valve diseases. However, TA diameter normative values and the extent of TA dynamic changes during cardiac cycle remain to be established. METHODS: This was a prospective, cross-sectional study of 219 healthy volunteers (mean age, 43 ± 15 years; 57% women), using conventional two-dimensional transthoracic echocardiographic (2DE) imaging to assess the variability of TA diameter measurement in relation to 2DE view and timing during cardiac cycle. TA diameter was obtained from apical right ventricular (RV)-focused four-chamber, parasternal long-axis RV inflow, and parasternal short-axis at aortic plane 2DE views at five time points during the cardiac cycle. Right atrial and RV volumes were measured using three-dimensional echocardiography. RESULTS: TA diameters differed significantly among the three 2DE views and changed significantly during the cardiac cycle in all views. Moreover, mean fractional shortening of TA diameter was 24 ± 6% in the four-chamber view, 20 ± 7% in the parasternal long-axis RV inflow view, and 29 ± 11% in the parasternal short-axis at aortic plane view. One multivariate linear regression analysis, age, gender, and right atrial and RV volumes were independently correlated with TA diameters and accounted for 55% of the variance of midsystolic TA diameter in the four-chamber view. CONCLUSIONS: This study provides references values for TA diameters and dynamics using 2DE imaging. Age, gender, and right chamber sizes, as well as the 2DE view and time during the cardiac cycle, significantly influenced TA diameters in healthy individuals. These data may help better identify TA dilatation using 2DE imaging for surgical planning.

Cardiovascular Dysfunction in Multiple Sclerosis.

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.

Normal mitral annulus dynamics and its relationships with left ventricular and left atrial function.

Mitral annulus (MA) geometry and dynamics are crucial for preserving normal mitral valve (MV) function. Static reference values for MA parameters have been reported, but the normal MA dynamics during the entire cardiac cycle remains controversial. MV full-volume datasets were obtained by three-dimensional transthoracic echocardiography from 50 healthy volunteers (18-74 years; 31 men) to assess MA changes in size and shape during entire cardiac cycle. Using simultaneous multiplanar review, projected MA area (MAA) and circumference (MAC), antero-posterior (AP) and anterolateral-posteromedial (ALPM) diameters, and sphericity index (SphI) were obtained at: mitral valve closure (MVC), mid- and end-systole (ES), early- (EDF) and late-diastolic filling, and end-diastole. MAA and AP diameter were the most "active" parameters, changing in all reference frames (p < 0.001). MAA and AP diameter started to contract before MVC (during the left atrial contraction), reaching their minimum at MVC. Maximum MAA occurred at ES, while maximum AP diameter and SphI occurred at EDF. MAA fractional shortening was 35 ± 10 %. AP diameter change was 25 ± 10 %. MAC, ALPM and SphI showed similar patterns during left ventricular (LV) systole, and remained unchanged during diastole. Fractional change was 35 ± 10 % for MAC, and 13 ± 8 % for ALPM diameter. Our study provides the normal dynamics of the MA during the entire cardiac cycle. It reveals "pre-systolic" contraction of the MA, related to left atrial (LA) contraction, and minimal MAA during early LV systole. Therefore, the normal MA dynamics relates to a "physiologic LA-LV coupling", and a complete MA contraction requires both and properly timed LA and LV systole.

Growth hormone deficiency in adults impacts left ventricular mechanics: a two-dimensional speckle-tracking study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 P < 0.01), 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 P < 0.05). 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. CONCLUSIONS: 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.

Normal left ventricular mechanics by two-dimensional speckle-tracking echocardiography. Reference values in healthy adults.

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.