© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12555

Echocardiography

Left Ventricular Twisting Modifications in Patients with Left Ventricular Concentric Hypertrophy at Increasing After-Load Conditions Amato Santoro, M.D., Federico Alvino, M.D., Giovanni Antonelli, M.D., Valerio Zac a, M.D., Susanna Benincasa, M.D., Stefano Lunghetti, M.D., and Sergio Mondillo, M.D. Division of Cardiology, University of Siena, Siena, Italy

Aims: Left ventricular hypertrophy (LVH) develops as a result of several clinical conditions, such as intensive training, hypertension, aortic valve stenosis. Aim of this study was to analyze the left ventricular twist (LVT) modifications in LVH patients with increasing after-load conditions. Methods: A total of 131 patients were enrolled: 17 healthy sedentary people (Hg), without concentric LVH; 45 water polo players (ATg); 22 patients with hypertensive cardiopathy (HPg); 47 patients with different degrees of aortic stenosis (ASg); all patients had concentric LVH, ejection fraction (EF) >54%, and were agematched. The left ventricular end-systolic wall stress (LV-ESWS) was used as index of after-load. Results: Left ventricular twist value showed a progressive increase from ATg to ASg, according to increasing after-load. Longitudinal left ventricular function by tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) was reduced in HPg and ASg. There was a negative correlation between LVT and longitudinal systolic function at TDI and STE (r =
0.4; P < 0.001;
0.23; P < 0.05). E/A ratio was lower in HPg and ASg than ATg and Hg. LVT was linearly related to LV-ESWS (r = 0.36; P < 0.01), E/A ratio (r = -0.59; P < 0.001), E/E′ ratio (r = 0.43; P < 0.001), age (r = 0.5; P < 0.001), relative wall thickness (RWT) (r = 0.38; P < 0.01), heart rate (HR) (r = 0.3; P < 0.05), maximum (G. max), and mean transvalvular gradient (G. mean) in ASg (r = 0.37; P < 0.01, r = 0.4; P < 0.01). RWT, E/A ratio, and HR were independent predictor of LVT (b = 0.23; P = 0.007;
0.44; P = 0.001; 0.17; P = 0.049). Only in ASg, G. mean was independent predictor of LVT (b = 0.44; P = 0.01). Conclusion: Left ventricular twist showed a linear trend at increasing after-load values to compensate the reduction in systolic longitudinal function in pathological LVH patients. (Echocardiography 2014;31:1265–1273) Key words: ventricular hypertrophy, ventricular twisting, strain Cardiac hypertrophic remodeling is commonly defined as a physiological or pathological adaptation that may occur during intensive training (athlete’s heart), pressure overload, or volume overload1,2 by means of different underlying mechanisms. The athlete’s heart is due to a left ventricular (LV) adaptation to longterm intensive training characterized by an increase in chamber size, wall thickness, and mass. These mechanisms depend on increase in maximal cardiac output and in stroke volume, decrease in resting heart rate (HR), and lower peripheral resistance.1 Pathological conditions such as hypertension (HP) and aortic stenosis (AS) determine modifications of LV pressure overload, LV wall thickness, and an increase in LV mass to maintain normal wall stress and unimpaired contractions. In HP, there is an increased Address for correspondence and reprint requests: Amato Santoro, MD, Le Scotte Hospital Division of Cardiology; Viale Bracci 17. 53100, Tuscany, Siena, Italy. Fax: +39-0577585377; E-mail: [email protected]

peripheral resistance, myocardial fibrosis, and increased deposition of extracellular matrix3. The high intraventricular pressure determined by increased after-load in AS leads to left ventricular hypertrophy (LVH) and impaired LV longitudinal function. Accordingly, LVH is an appropriate adaptive response, although it may also bring along adverse consequences like predisposition to ischemia and impairment of diastolic function.2–4 Speckle tracking echocardiography (STE) is a noninvasive tool for the assessment of LV global and regional function. STE offers the opportunity to track myocardial deformation independently of both cardiac translation and the insonation angle.5 The varying orientation of LV muscle fibers across the LV wall—from a right hand helix in the subendocardium, through circumferential fibers in the midwall, to a left hand helix in the subepicardium—determines the shortening of obliquely oriented LV fibers, which in turn 1265

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generates a wringing motion responsible for LV twisting (LVT).5,6 In athletes, the twisting deformation is low at rest and it is considered a compensatory mechanism to optimize stroke volume during effort.7–9 In HP patients, LVT is increased and it is considered a mechanism to maintain an adequate ejection fraction (EF) despite a reduction in longitudinal function of LV.10 In AS, LVT has the same function as it maintains a good LV global systolic function despite a reduction in longitudinal function as reported in previous studies.4 The aim of this study was to compare the modifications of LVT in 3 groups of patients with concentric LVH and preserved EF, and relationships among LVT, systolic, and diastolic functions at increasing after-load conditions. Methods: Study Population: All work was in compliance with the declaration of Helsinki. We enrolled 131 age-matched patients, who gave their written informed consent for the study. All patients showed concentric LVH. Concentric LVH was defined as the echocardiographic evidences of (relative wall thickness) RWT > 0.42, increased LV mass indexed for body surface area (LVMi) >115 g/m2 for men calculated according to Devereux formula, and adequate echocardiographic quality.11 Patients were categorized in 4 groups according to disease and after-load status. We calculated left ventricular end-systolic wall stress (LV-ESWS) as a reliable index of LV after-load. It is defined as the force acting per unit area of the section of the ventricle wall, may be calculated by applying the law of Laplace; wall stress is directly proportional to the intraventricular pressure and radius of curvature of the wall, and inversely proportional to the wall thickness. LV-ESWS was calculated with the following formula12,13:

amateur competitive athletics as control group (2) Athletes group (ATg) included 45 competitive water polo players with concentric LVH. They competed in a professional Italian championship. They trained every day for 2 hours and half a day, except on Sunday; they had a training background of at least 5 years. (3) Hypertensive group (HPg) was composed of 22 patients with hypertensive cardiopathy and concentric LVH cross-matched for LV mass index. These patients were on medication (usually controlled with only one drug) and under regular medical control; they presented blood pressure 54%. Oscillometric semiautomatic sphygmomanometers were used to measure blood pressure. The device used was Datascope Accutorr Plus Soma technology; it was validated according to

ðPESÞ  ðDESÞ=ðHESÞ  ð1 þ HES=DESÞ  0:34 Left ventricular end-systolic wall stress was in g/cm2, PES, which stood for LV end-systolic pressure, was in mmHg, DES and HES were in LV end-systolic dimension and wall thickness in cm, and 0.34 was the factor for converting PES from mmHg to g/cm2. (1) Healthy group (Hg) included 17 healthy sedentary people, with no evidence of cardiac hypertrophy or any cardiovascular disease, of whom none was engaged in any kind of routine training program or 1266

TABLE I Aortic Valve Characteristics of ASg Aortic Valves Parameters CW (m/sec) G. max (mmHg) G. med (mmHg) a AVA cm2 f AVA cm2

3.0 62.3 35.9 1.3 1.2

    

0.86 3.4 19.1 0.31 0.35

CW = transaortic valve continue Doppler velocity wave; G. max = maximum transaortic gradient value; G. med = mean transaortic gradient value; a AVA = anatomic aortic valve area; f AVA = functional aortic valve area.

Ventricular Torsion in Different Cardiac Hypertrophy

standardized protocols and their accuracy was checked periodically through calibration in a technical laboratory.15 Measurement of blood pressure at the upper arm and cuff and bladder dimensions was adapted to the arm circumference, according to ESC guidelines.16 Exclusion criteria from the study were: diabetes mellitus, another valvular disease (mitral stenosis of any degree, more than mild mitral and aortic regurgitation), coronary artery disease (CAD), b-blockers assumption, pulmonary disease, arrhythmias, left bundle branch block, pacemaker implantation, atrioventricular block of any degree. Echocardiographic assessment – Standard Echocardiography: echocardiographic examinations were performed using a high-quality echocardiograph equipped with a 3.5 MHz probe (Vivid 7, GE, Milwaukee, WI, USA). Left ventricular measurements were performed by M-mode imaging from parasternal long-axis views, in accordance with current American Society of Echocardiography recommendations. LV ejection fraction (LVEF) was obtained using the biplane modified Simpson’s method. Standard pulsed Doppler interrogation of LV inflow was performed from the apical four-chamber view. Left atrial (LA) volume was calculated using the biplane method of disks and then indexed to body surface area (BSA). Tissue Doppler (TDI) waves imaging of mitral annular motion was performed from the apical four-chamber view, and mean systolic velocity peak (S′), early diastolic velocity peak (E′), and late diastolic velocity peak (A′) were calculated by averaging septal and lateral wall values. E′ was used as a relatively preload-independent measure of LV relaxation.13 The ratio of early to late annular velocity (E′/A′) was determined as a parameter of diastolic function, as well as the LV filling index, by the ratio of transmitral flow velocity to annular velocity (E/E’).13 Frame rate used for TDI measurements was 60–75 frames/sec. TDI was performed by transducer frequencies of 3.5 MHz. Speckle Tracking Echocardiography: Speckle tracking echocardiography was performed by the acquisition of parasternal short-axis views by conventional 2D grayscale echocardiography at the basal and apical levels, at the end of a breathe hold cycle, with the standard and stable ECG recording. Short-axis recordings were obtained from a standard parasternal probe position for the basal plane, and from a more distal anterior or anterolateral position for the apical plane. To standardize acquisitions, the basal plane was acquired at mitral valve plane, whereas the apical plane was identified distally to the papillary muscles as that just

proximal to the level where LV cavity end-systolic obliteration occurred. Frame rate (range 65–90 frames/sec) and probe frequency (1.7–2.0 MHz) were adjusted to optimize image acquisition, and both image depth and sector width were set to combine temporal resolution with adequate spatial definition. STE analyses were performed off line using a dedicated software package (EchoPac, GE Medical Systems, Waukesha, WI, USA) by 2 experienced investigators who were not involved in image acquisition and who were unaware of the results of standard echocardiographic examination.5 Reproducibility of STE measurements was evaluated in a subset of 30 randomly selected subjects. For assessment of inter-observer variability, images were independently analyzed by a second experienced investigator, blinded to the results of standard echocardiography and not involved in image acquisition. Coefficients of variation and intraclass correlation for intra-observer analysis were of 5.9%, r = 0.93; P < 0.0001 demonstrating a low intra- and inter-observer variability and a good test reliability of STE parameters. Three consecutive cardiac cycles for each short-axis view image were obtained during end-expiratory breath. After manual demarcation of LV endocardium by a point-and-click approach, epicardial tracing was automatically generated by the system, thus delineating the strain region of interest throughout the entire myocardial circumference. The software algorithm then automatically segmented the LV circumference into 6 myocardial segments and tracked the motion of LV myocardial speckles throughout the cardiac cycle, generating rotation-time curves for each segment. The global basal and apical rotations were estimated as the average angular displacement of 6 myocardial segments during systole. By convention, counterclockwise rotation, as viewed from LV apex, was marked as a positive value, whereas clockwise rotation was expressed as a negative value. Rotation angles were expressed in degrees (°). LVT curve was automatically generated as the net difference between mean apical and basal rotation at isochronal points. Peak twist angle during ejection phase was assumed as LVT. LV torsion (LVTor) was LVT indexed for LV length. The degree of untwisting rate (UTW) was defined as the directional reversal of systolic counterclockwise twist during diastole and as percentage of untwisting (UTW%) during isovolumic relaxation time (IVRT); time of UTW was the time to peak untwisting velocity measured from mitral valve opening.17–18 LV longitudinal deformation, defined as peak ventricular longitudinal 1267

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strain (LVS) was calculated by average of fourand two-chamber longitudinal ventricular strain during systole. LV basal circumferential deformation (BCVS) and LV apical circumferential deformation (ACVS) in short-axis view were also obtained.

Hg showed normal values of these parameters. LV-ESWS values were lower in ATg compared to others groups. HPg and ASg had higher values of LV-ESWS among all analyzed groups. Systolic Parameters Results: All systolic parameters are summarized in Table III. Longitudinal LV function evaluated by TDI with lateral and septal systolic wave (S′) and with STE was reduced in HPg and ASg compared to ATg and Hg. In fact, there were statistically significant differences among ATg and HPg, ATg and ASg, Hg and HPg, and Hg and ASg (P < 0.05). LVT values showed a progressive increase from ATg to ASg, at increasing LV-ESWS values. ASg showed the highest LVT values, while the lowest LVT was found in ATg; LVT value was not statistically different between HPg and ASg. Apical rotation of ATg and Hg were lower than values of HPg and ASg. The Hg had the highest values of LVS; the ATg, HPg and ASg showed, respectively, a reduction in LVS with significant statistical difference between ATg and ASg (P < 0.05) and Hg and HPg (P < 0.05).

Statistical Analysis: Continuous data were expressed as means  standard deviation (SD). Statistical comparison between the groups was performed using one-way analysis of variance (ANOVA). Pearson’s correlation coefficients were calculated to assess the relationships between continuous variables. Spearman test was used to determine nonlinear correlations. A multiple stepwise linear regression analysis was performed to assess independent predictors of LV diastolic function and LVT. Beta value (b) was the regression coefficient for stepwise multiple linear regression; the b coefficient indicated how the dependent variable responded to changes of the independent variable, after adjusting for all other covariates in the model. Analyses were performed using SPSS 20 for Windows (SPSS Inc., Chicago, IL, USA).

Diastolic Parameters Results: All diastolic parameters are shown in Table IV. Diastolic function in Hg and ATg was normal, as demonstrated by a normal transmitral flow pattern. UTW and time of UTW were lower in ATg and Hg respect HPg and ASg; UTW% at IVRT had greater values in ATg and its impairment was shown in HPg and ASg. No patients had pseudonormal LV filling at pulsed Doppler measurements.

Results: The main characteristics of study population are shown in Table II; comparisons with P < 0.05 are commented in the text. HR was significantly different between ATg and other groups with P < 0.05. Standard echocardiographic measures and echocardiographic systolic parameters are summarized in Table III. Left ventricular end-diastolic diameter (EDD) in ATg was significantly greater than ASg and than Hg; LV wall thickness exhibited mild differences in interventricular septum (IVS). ATg, HPg, and ASg showed increase in LVMi and RWT, resulting in concentric LVH, while

Correlations of LVT: Correlation of LVT are shown in Figure 1. All significant statistically correlations of LVT are summarized in Table V. Stepwise multivariate

TABLE II Biometric Data of Study Population Healthy (n = 17) Age (years) Weight (kg) Height (cm) BMI (g/m2) HR (ppm) SBP (mmHg) DBP (mmHg) BSA (m2)

40.4 76.1 180.4 23.3 75.4 119.2 72.4 1.9

       

9.2 6.3* 4.9§∼ 1.7§b 9.3* 7.2§b 5.1 0.1*

Athletes (n = 45) 39.2 79.6 183.4 25.2 59.2 115.7 71.3 2

       

6.5 9.8‡ 9.6†‡ 1.7†‡ 6.8†‡ 6.3†‡ 6.2 0.2†,‡

Hypertensive (n = 22) 47.6 83.6 172.5 27.9 76.7 147.5 82.7 1.9

       

7.9 14.4a 8.2a 4.2 8.7 15.4a 13.4 0.2

Aortic Stenosis (n = 47) 48.3 70.3 173.5 26.1 78 130.5 75.4 1.9

       

9.2 14.6 14.6 5.4 12.3 7.4 8.2 0.7

BMI = body mass index; HR = heart rate; SBP = systolic blood pressure; DBP = diastolic blood pressure; BSA = body surface area. *P < 0.05 athletes vs. healthy; †P < 0.05 athletes vs. hypertensive; ‡P < 0.05 athletes vs. aortic stenosis; §P < 0.05 healthy vs. hypertensive; ∼p