Cardiac Mechanics in Patients with Systemic Hypertension with Normal EF : A Speckle-Strain Imaging Study

Background: Conventional transthoracic echocardiography (TTE) and tissue Doppler imaging (TDI) are usually unable to reveal very early subtle abnormalities in left ventricular (LV) systolic function caused by hypertension, prior to manifestation of hypertrophy (LVH). This study was undertaken to assess whether speckle tracking echocardiography (STE) provides more insight into early hypertension induced LV systolic dysfunction, with the purpose of identifying patients at higher risk for heart failure (HF). Methods: Fifty patients (54.16 ± 8.4 years) and 50 controls (52.17 ± 8.6 years) were enrolled. According to the presence or absence of LVH, patients were classified as LVH(+) and LVH(–), respectively. Global longitudinal function was calculated by TDI, global strains [longitudinal (LS), radial (RS), and circumferential (CS)] were assessed by STE. Results: Conventional TTE showed a normal systolic function in all patients. TDI was able to detect a systolic dysfunction only in the LVH(+) group (P < 0.001) whereas STE revealed an impairment of systolic LS and CS in all patients, including those without hypertrophy (P =<0.0001). Furthermore, in the LVH(+) group, STE showed increased RS . Conclusion: In hypertensive patients, STE provides more detailed information than conventional echocardiography and TDI, since it reveals a systolic dysfunction before hypertrophy occurs (Stage A of ACC/AHA classification of HF) and identifies some early LV mechanic changes that might improve the clinical management of these patients Raghvendra Choudhary , Deepak Maheshwari , Puneet Rijhwani , Monika Rathore 1. Department of Cardiology, SMS Medical College and Hospital, Jaipur, Rajasthan, India. 2. Department of Medicine; Mahatma Gandhi University of Medical Sciences & Technology, Jaipur, Rajasthan, India. 3. Department of Community Medicine, SMS Medical College and Hospital, Jaipur, Rajasthan, India. Cardiac Mechanics in Patients with Systemic Hypertension with Normal EF: A Speckle Strain Imaging Study 10.14302/issn.2329-9487.jhc-13-272 Corresponding Author: Dr. Raghvendra Choudhary ; 6/5 Heerabagh Flats, Jaipur, India. 302004. ; Phone no: +919414262690 Email: drraghven10@gmail.com


Background:
[3] Identifying subclinical left ventricular (LV) systolic dysfunction among hypertensives might be helpful in identifying patients at higher risk of developing heart failure.
Also, given the prevalence of hypertension in the population, identifying patients at high risk for heart failure might permit targeted preventive strategies.Early detection of left ventricular (LV) systolic dysfunction in affected patients is, therefore, a crucial issue.
[18][19][20] It is previously demonstrated that M-mode echocardiography can be used to measure circumferential shortening at the mid-wall (FSmw,%), 21- 22 a measure of regional circumferential strain.Reduced FSmw is prevalent among hypertensives with hypertrophic remodeling, 21 and de Simone and coworkers have shown that low FSmw in relation to stress is a marker of poor outcome. 22However, FSmw is related to ventricular geometry-the relative wall thickness(RWT). 21Newer methods, such as 2D -speckle imaging, appear to provide a direct, angle and geometry independent measure of circumferential strain (CS). 235][26][27] This technique, therefore, can provide new mechanistic insight into systolic dysfunction even in patients without structural cardiac alterations (Stage A of ACC/AHA classification of HF). 28e aim of the current case-control study was to use speckle tracking imaging as well as standard echo techniques to identify subclinical abnormalities in LV function among hypertensives, as compared to normal controls.

Aims and Objectives
To assess the subtle differences in the LV principal strains for characterizing features of subclinical LV dysfunction in patients with systemic hypertension and preserved LV systolic pump function. The age-matched control group included normotensive healthy subjects free from cardiovascular risk factors.

Study Population.
The protocol was approved by the local research Ethics Committee and a written informed consent was obtained from each subject.

Echocardiography:
Conventional Measurements: Two-dimensional (2D) grayscale harmonic images were obtained in the left lateral position using a commercially available ultrasound system (i-33 PHILIPS) equipped with a cardiac M4S transducer.All measurements were averaged from three heart beats.
2] The enddiastolic relative wall thickness (RWT) was also calculated, and a cut-off value of ≥0.45 was taken into account to define a concentric remodeling. 31e LV mass was determined with the area-length method, (31)

Global Longitudinal Function by TDI:
Color TDI cineloops of three cardiac cycles from both four-and two-chamber views, obtained at endexpiratory apnea, were acquired and digitally stored.
Gains were minimized to have a clear tissue signal with minimal background noise.To acquire the highest tissue velocities, the angle between the Doppler beam and mitral annulus was adjusted to a minimal level (<20º).
From stored color TDI loops, a PW Doppler sample was set, offline, at the level of the septal and lateral corner (apical four-chamber view), and anterior and inferior corner (apical two-chamber view) of mitral annulus.The peak of systolic (S'), early diastolic velocity (E') and late diastolic velocity (A') was calculated for each corner.The results were averaged to obtain a mean value of S', E' and A'.

Strains by Speckle Tracking
Echocardiography.

Pearson's Linear Correlations:
The following relationships have been observed: (1) Systolic blood pressure was inversely related with LS (r = -0.73,P < 0.0001); CS (r = -0.61,P < 0.0001); and positively with RS (r = 0.22, P = 0.02).( 2 Echocardiography.This technique permits the detection of early LV diastolic function changes in hypertension, 33 and also reveals that, in hypertensive patients free from clinical manifestations of HF, the earliest myocardial impairment involves the longitudinal fibers. 34e main findings of this research are: (1) Hypertension results in early changes of LV mechanics that begin even before LV hypertrophy  (2) In hypertension, alterations in LS and CS, as well as RS changes are related to LV concentric hypertrophy (Stage B).

LV Mechanics in Patients with Normal Geometry (Stage A):
It is well known, and confirmed by this study, that a preclinical systolic dysfunction occurs in hypertensive patients with LV hypertrophy. 35,36 have observed, in addition, an impairment of longitudinal and circumferential systolic function even in patients with normal LV geometry.In this respect, STE appears more sensitive than both conventional echocardiography and TDI in identifying a reduction of intrinsic myocardial contractility, evident in hypertensive patients even long before LV hypertrophy becomes detectable.This finding highlights the advantages of 2D strain over TDI in early identifying LV systolic function impairment.
These early changes of myocardial contractility may be secondary to hemodynamic and/or biochemical alterations.The increased end-systolic wall stress, an expression of afterload, as well as the loading conditions, are likely to play a role in determining the longitudinal dysfunction in HHD.On the other hand, the With regard to the biochemical changes, myocardial fibrosis is one of the factors responsible for myocardial function deterioration in hypertension 37,38 in affected patients with normal EF, impaired LS and increased LV torsion are directly related with serum levels of tissue inhibitor of metalloproteinase-1 matrix, a marker of myocardial fibrosis. 39This suggests that abnormal collagen turnover and myocardial fibrosis may contribute to early LV contractile dysfunction. 40,41On the other hand, in this study we observed that RS is preserved in hypertensive patients without structural LV changes.

Hypertrophy (Stage B):
[49][50][51] Subendocardium is susceptible to the deleterious effects of both interstitial fibrosis and hypoperfusion, to the extent that in HHD impairment of the subendocardial function results in abnormal longitudinal function. 52This is also suggested by a recent study based on 3D wall motion tracking analysis, demonstrating that myocardial strain pattern depends on LV adaptative responses to high blood pressure. 53Our results show that in a relatively late stage of HHD, corresponding to stage B of HF, additional LV changes occur, such as increase of RS, suggesting an involvement of mid-myocardial layers.
The finding is consistent with the results of a recent study, demonstrating that in hypertension LV longitudinal systolic function progressively deteriorates. 54

Limitations:
A limitation of this study is the small size of the sample; this is dependent on the inclusion of highly and the LV mass index was calculated as ratio LV mass/BSA (g/m²).The diagnosis of LV hypertrophy was based on a LV mass index (LVMI) >102 g/m² in men and >81 g/m² in women.(32)Hypertensive patients were divided in two subgroups: subjects without LV hypertrophy [LVH(-)] ,and subjects with LV hypertrophy [ LVH(+)].
) The systolic blood pressure was also inversely related with S' (r = -0.75,P < 0.0001); E' (r = -0.65,P < 0.0001); and positively related with A' (r = 0.55, P < 0.0001).Similar correlation were found with diastotic blood pressure.(3)In hypertensives we found a significant inverse relation between LV mass and indices of global LV systolic function, including both LS (r = -0.1;p<0.001) and CS ( r = -0.59;p<0.0001)Discussion: Hypertensive patients without symptoms and/or signs of HF and with normal contractile function, as explored with conventional echocardiography, show subtle adaptative changes of LV systolic mechanics, which can be identified only by Speckle Tracking

Table 2 ) TDI and Speckle Tracking Analysis:
Three consecutive endexpiratory cycles, in grayscale (frame rate = 60 to 80 frames/s) stored for each view and subsequently transferred to an Q-LAB workstation The analysis of 2D strain was performed offline, using a semiautomatic tracking of LV.After manually tracking the endocardial border on a 2D image endsystolic frame, the software automatically tracked myocardial motion, creating six equidistant speckle tracking regions of interest for each image.Global LS, CS, and RS were obtained by calculating the average strain derived by myocardial tracking from each viewStatistical Analysis:Data were expressed as mean ± SD.Statistical analysis was performed using the SPSS statistical software (SPSS v.17 for Windows, SPSS Inc., Chicago, IL, USA).For any parameter, independent t-test and ANOVA were used to compare variables between different groups.The chi (Continued on page 14) Freely Available Online www.openaccesspub.org| JHC CC-license DOI : 10.14302/issn.2329-9487.jhc-13-272Vol-1 Issue -2 Page No-14 square test and Fisher's exact test were used for categorical variables.Linear regression analysis, with Pearson's coefficient, was used to estimate correlation between continuous variables.P values ≤ 0.05 were considered significant regarding: age, gender and heart rate (P = ns).34%of hypertensive subject had evidence of concentric remodeling.As expected, most controls had normal LV mass index and geometry.No difference between LVH (-) and LVH (+) patients was found with respect to systolic (152.3±8.89mmHg vs. 157.2±7.38 mmHg, P = ns) and diastolic blood pressure (97.36±7.27mmHg vs. 99.24±6.74mmHg,P = ns).LV Function by Conventional Echocardiography: LVEF was normal both in LVH(-) and in LVH(+) patients; LV wall thickness, RWT were significantly increased in both LVH(-) and LVH(+) patients with respect to controls.As expected, thickness, RWT and LVMI were significantly higher in LVH (+) than in LVH(-) patients (P < 0.001).The RWT in the LVH(+) group was 0.47 ± 0.09%, as an expression of concentric hypertrophy.(On the other hand, STE revealed relevant changes in LV mechanics even in patients with normal geometry (LVH(-)): these subjects, characterized by normal LV function on TDI, had an impaired systolic LS (-16.3±2.01 % vs. -19.31±1.87%, P = <0.0001)and CS (-17.31±2.28% vs. -18.98±1.56%, P = <0.0001),with normal RS (19.22±1.90% vs. 18.88±1.54%, P = 0.38) when compared to healthy subjects (Figs. 1).Moreover, in the LVH(+) patients STE revealed lower LS (-12.91 ±1.67 % vs. -19.31±1.87,CS -14.62 ±1.216%, vs -18.98±1.56P<0.001, Fig. 1) and higher (Continued on page 15)