© 2013, Wiley Periodicals, Inc. DOI: 10.1111/echo.12482

Echocardiography

Left Ventricular and Atrial Functions in Hypertrophic Cardiomyopathy Patients with Very High LVOT Gradient: A Speckle Tracking Echocardiographic Study Kursat Tigen, M.D.,* Murat Sunbul, M.D.,* Tansu Karaahmet, M.D.,‡ Cihan Dundar, M.D.,† Beste Ozben, M.D.,* Ahmet Guler, M.D.,† Altug Cincin, M.D.,* Mustafa Bulut, M.D.,† Ibrahim Sari, M.D.,* and Yelda Basaran, M.D.* *Department of Cardiology, Marmara University Faculty of Medicine, Istanbul, Turkey; †Department of Cardiology, Kartal Kosuyolu Heart Education and Research Hospital, Istanbul, Turkey; and ‡Department of Cardiology, Acibadem University Faculty of Medicine, Istanbul, Turkey

Background: Determination of myocardial deformation (strain) by two-dimensional (2D) speckle tracking echocardiography (STE) is a new method for evaluating left ventricular (LV) regional function in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to assess LV and left atrial (LA) functions with 2DSTE in HCM patients and to investigate relation between strain analysis and LV outflow tract (LVOT) gradient. Methods: Forty consecutive HCM patients (26 male, mean age: 47.7  15.2 years), and 40 healthy volunteers (22 male, mean age: 46.6  11.2 years) were included in the study. All subjects underwent a transthoracic echocardiography for evaluation of LV and LA functions with 2DSTE. The HCM patients were divided into 2 groups according to the presence of resting LVOT gradient >100 mmHg. Results: Left ventricular global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) were significantly lower in patients with HCM compared with controls ( 20.3  3.6% vs. 24.1  3.4% P < 0.001, 38.1  12.8% vs. 44.8  10.2% P = 0.012, and 22.0  4.4% vs. 23.9  4.0% P = 0.045, respectively). Although basal and apical rotation were similar between the groups, mid-rotation was significantly clockwise in HCM patients ( 1.53  2.06° vs. 0.05  1.7° P < 0.001). Both LA reservoir functions and LA conduit functions were significantly lower in HCM patients (21.6  9.1% vs. 39.4  10.6% P < 0.001, and 10.5  4.3% vs. 15.7  5.3%, P < 0.001). Fifteen patients had a resting LVOT gradient of >100 mmHg and they had significantly decreased GLS, twist and untwist compared to the HCM patients with lower resting LVOT gradient ( 18.7  2.3% vs. 21.2  3.9% P = 0.016, 19.4  4.3° vs. 23.5  7.4° P = 0.038 and 94.0  29.1°/sec vs. 134.9  55.8°/sec, 0.005, respectively). Although basal and apical rotation were similar between the 2 groups, mid-rotation was significantly clockwise in HCM patients with higher LVOT gradient ( 2.52  1.76° vs. 0.96  2.03°, P = 0.018). Correlation analysis revealed that LVOT peak velocity was associated with GLS (r = 0.358, P = 0.023), LV mid-rotation (r = 0.366, P = 0.024), and LV untwist (r = 0.401, P = 0.013). Conclusions: Left ventricular and LA functions are impaired in patients with HCM. 2DSTE is useful in determining patients with impaired myocardial mechanics. High LVOT gradient may be one of the responsible factors that trigger deterioration of LV longitudinal strain and twist mechanics in patients with HCM. Further studies are required to clarify the preliminary results of this study. (Echocardiography 2014;31:833–841) Key words: hypertrophic cardiomyopathy, speckle tracking echocardiography, strain, twist, left ventricular, left atrial Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular (LV) hypertrophy of various morphologies, with variety of clinical manifestations and hemodynamic dysfunctions.1 HCM patients usually have certain abnormalities Address for correspondence and reprint requests: Murat Sunbul, M.D., Marmara University Education and Research Hospital, Fevzi Cakmak Mahallesi, Mimar Sinan Caddesi, No: 41, Pendik/Istanbul. Fax: +90 216 657 06 95; E-mail: [email protected]

including diastolic dysfunction, myocardial ischemia, mitral regurgitation, and LV outflow obstruction related to excessive myocardial hypertrophy.1 These abnormalities can cause serious symptoms such as chest pain, palpitations, dyspnea, fatigue, and syncope. Determination of myocardial deformation (strain) by two-dimensional (2D) speckle tracking echocardiography (STE) is a new method for evaluating myocardial mechanics. 2DSTE has 833

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been used to evaluate LV regional function in patients with HCM.2,3 It may correlate with myocyte disarray and fibrosis and can be used to assess LV relaxation and filling pressures in patients with obstructive HCM.2,3 The aim of this study was to assess LV and left atrial (LA) functions with 2DSTE in HCM patients and to explore any relation between strain analysis and LV outflow tract (LVOT) gradient. Materials and Method: The investigation complies with the principles outlined in the Declaration of Helsinki. The study was approved by the local ethics committee and all participants gave written informed consent before participating. The study population was consisted of 48 consecutive patients with diagnosed HCM. The diagnosis of HCM was based on presence of typical clinical, electrocardiographic (ECG), and echocardiographic features, with global or segmental ventricular myocardial hypertrophy (diastolic wall thickness ≥ 15 mm), occurring in the absence of any other cardiac or systemic disease such as Fabry’s disease and cardiac amyloidosis.4 All study population underwent a transthoracic echocardiography for evaluation of LV and LA functions with 2DSTE. After excluding the patients with impaired LV systolic function (ejection fraction < 55%), significant valvular heart disease, history of coronary artery disease, malignancy, systemic arterial hypertension, presence of significant aortic stenosis, storage disorders such as Fabry’s disease and cardiac amyloidosis, as well as the patients with poor echogenicity, the remaining 40 HCM patients were enrolled in the study. The control group included 40 healthy age- and sex-matched volunteers free of cardiovascular risk factors and without any cardiac and systemic disease. Standard Echocardiography and 2DSTE: All patients underwent a complete echocardiographic examination with a commercially available echocardiography device (Vivid 7, GE Vingmed Ultrasound AS, Horten, Norway) by a single experienced cardiologist. Data acquisition was performed with a 3.5 MHz transducer at a depth of 16 cm in the parasternal and apical views (standard parasternal short-axis from midventricular level, apical long-axis, two-chamber, and four-chamber images). Standard M-mode, 2D, and color-coded tissue Doppler imaging (TDI) images were obtained during breath hold, stored in cine loop format from 3 consecutive beats and transferred to a workstation for further offline analysis (EchoPAC 6.1; GE Vingmed Ultrasound AS). Gain settings, filters, and pulse repetitive frequency were adjusted to optimize color 834

saturation, and a color Doppler frame scanning rate of 100–140 Hz was used for color TDI images and greyscale images at a frame rate of 44–82 frames/sec. Conventional echocardiographic parameters were measured according to the guidelines of the American Society of Echocardiography and LV ejection fraction (EF) was calculated using the biplane Simpson’s method.5 Relative wall thickness, mid-wall fractional shortening, LV mass index, and LA volume index were calculated as previously described.5 Left ventricular outflow tract obstruction was considered when a gradient of 30 mmHg was detected at rest or with the Valsalva maneuver. HCM patients were divided into 2 groups according to the presence of high resting LVOT gradient (>100 mmHg) based on the previous studies of aortic stenosis that had shown an association between higher peak aortic jet velocity (>5.0 m/sec) and poor prognosis with a high cardiovascular risk and rapidly functional deterioration.6,7 Multidirectional analysis of LV strain (in the radial, circumferential, and longitudinal directions) was performed using 2D speckle tracking imaging as previously described.8,9 Apical four-chamber, two-chamber and long-axis views were used for longitudinal strain and strain rate analysis while parasternal short-axis (SAX) views at 3 levels (the base, the level of papillary muscles, and the apex) were used for circumferential and radial strain, strain rate, twist, and torsion analysis. End-systolic regions of interest were traced on the endocardial cavity (minimum cavity area) using a point-and-click approach with special care taken to adjust the tracking of all endocardial segments. A second larger concentric circle was then automatically generated and manually adjusted near the epicardium. Speckle tracking automatically analyzed frame-by-frame the movement of the speckles over the cardiac cycle. Each image was divided into 6 standard segments, corresponding strain curves were obtained. The mean strain values were calculated for each SAX view, apical long-axis, apical fourand two-chamber views, as the sum of endsystolic strain values in 6 segments, divided by 6. Global longitudinal strain (GLS) was derived from the average of longitudinal strain values in the apical four-chamber, two-chamber, and longaxis views. Global circumferential strain (GCS) and global radial strain (GRS) were derived from the average of 6 mid-circumferential strain and mid-radial strain values. Two-dimensional speckle tracking analysis of parasternal SAX views at the base and the apex, revealed LV “rotation” and “rotation rate” curves as the angular displacement and the velocity of displacement of the LV around its central axis. Negative values indicated clockwise, whereas

Myocardial Mechanics in Hypertrophic Cardiomyopathy

positive values indicated counterclockwise rotation. Left ventricular “twist” and “twist rate” were defined as the net difference of LV peak systolic “rotation” and “rotation rate’ between basal (clockwise) and apical (counterclockwise) shortaxis planes. Values were expressed in “°” and “°/sec,” respectively. “Untwist” was expressed as a diastolic angular motion of the LV, opposite to twist. “Untwisting rate” (°/sec) was defined as the peak twist rate during early diastole. LV torsion was calculated as the net LV twist normalized with respect to ventricular diastolic longitudinal length between the LV apex and the mitral plane (LV torsion [°/cm] = [apical LV rotation basal LV rotation]/LV diastolic longitudinal length). Mid-rotation was examined to detect the “null velocity” segment within the left ventricular cavity. The difference between left ventricular mid-segment and basal segment rotation values was defined as mid-rotation, indicating the net twist between these segments. For the LA speckle tracking analysis, LAfocused images in apical four-chamber view were obtained. A minimum frame rate of 40 frames per second was required for the reliable operation of this program. For 2D speckle tracking strain analysis, a line was manually drawn along the LA endocardial border from the apical four-chamber view after atrial contraction, when the LA was at its minimum volume, using the point-and-click approach as previously described.8 The software then automatically generated additional lines near the atrial epicardium and mid-myocardial line, with the narrowest region of interest (ROI). The ROI then included the entire LA myocardial wall and was adjusted for thickness. The software generated strain curves for each atrial segment. The values of peak early and late diastolic longitudinal strain were determined as left atrial reservoir (LA-Res) and conduit (LA-Con) function. Statistical Analysis: Statistical analyses were performed using SPSS 20.0 statistical package for Windows (IBM SPSS, Armonk, NY, USA). Continuous data were expressed as mean  standard deviation, whereas categorical data were presented as number of patients. Chi-square test was used for comparison of categorical variables, whereas Student’s t-test or Mann–Whitney U-test were used to compare parametric and nonparametric continuous variables, respectively. Correlation analysis was performed by Spearman’s correlation test. A value of P < 0.05 was considered statistically significant. Results: The study population included 40 patients with HCM (26 male, mean age: 47.7  15.2 years),

and 40 healthy volunteers (22 male, mean age: 46.6  11.2 years). The characteristics and conventional echocardiographic parameters of the patients and controls are expressed in Table I. In brief, LV wall thicknesses, dimensions and volumes, LA dimensions and volumes, LVTDI-based velocities and E/e ratios were all significantly different between HCM patients and the control group. The speckle tracking echocardiographic measurements of the patients and the controls are shown in Table II. LV GLS, GRS, and GCS were significantly lower in patients with HCM compared with those of controls ( 20.3  3.6% vs. 24.1  3.4% P < 0.001, 38.1  12.8% vs. 44.8  10.2% P = 0.012, and 22.0  4.4% vs. 23.9  4.0% P = 0.045, respectively) (Fig. 1). Although basal and apical rotation were similar between the 2 groups, mid-rotation was significantly clockwise in HCM patients ( 1.53  2.06° vs. 0.05  1.7°, P < 0.001). Both LA reservoir functions and LA conduit functions were significantly lower in HCM patients (21.6  9.1% vs. 39.4  10.6% P < 0.001, and 10.5  4.3% vs. 15.7  5.3% P < 0.001). Hypertrophic cardiomyopathy patients were divided into 2 groups according to their LVOT gradient values. The characteristics and conventional echocardiographic parameters were similar between 2 groups except for LA diameter measurements (Table III). Fifteen patients had a resting LVOT gradient of >100 mmHg and they had significantly decreased GLS, twist and untwist rate compared with the HCM patients with lower resting LVOT gradient ( 18.7  2.3% vs. 21.2  3.9% P = 0.016, 19.4  4.3° vs. 23.5  7.4° P = 0.038, and 94.0  29.1°/ sec vs. 134.9  55.8°/sec, and P = 0.005, respectively). Although basal and apical rotation were similar between the 2 groups, mid-rotation was significantly clockwise in HCM patients with higher LVOT gradients ( 2.52  1.76° vs. 0.96  2.03°, P = 0.018) (Table IV) (Fig. 2). Correlation analysis revealed that LVOT peak velocity was associated with GLS (r = 0.358, P = 0.023), LV mid-rotation (r = 0.366, P = 0.024) and LV untwist (r = 0.401, P = 0.013). E/e ratio as an indicator of elevated LV end-diastolic pressure correlated with LVs (r = 0.590, P < 0.001), LVe (r = 0.789, P < 0.001) LVa (r = 0.516, P < 0.001), left atrial volume index (LAVI) (r = 0.435, P < 0.001), GLS (r = 0.317, P = 0.005), GRS (r = 0.307, P = 0.007), LV mid-rotation (r = 0.333, P = 0.004), LA-Res (r = 0.508, P < 0.001), LA-Con (r = 0.384, P = 0.001), and LVOT Gradient (r = 0.718 P > 0.001).

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TABLE I Characteristics and Conventional Echocardiographic Parameters of the Patients and Controls

Age (years) Male sex (n, %) BSA (m2) E velocity (m/sec) A velocity (m/sec) DT (ms) LV-s (cm/sec) LV-e (cm/sec) LV-a (cm/sec) E/e IVS (mm) PW (mm) LVEDD (mm) LVESD (mm) LAD (mm) LAVI (mL/m²) EF (%) Stroke Volume (mL) LVEDV (mL) LVESV (mL) LV Mass Index (g/m²) RWT MWFT (%)

Patients with HCM (n = 40)

Controls (n = 40)

P

47.7  15.2 26 (65%) 1.87  0.20 0.88  0.23 0.83  0.24 194.1  59.6 5.6  1.5 4.9  2.1 5.8  1.9 20.2  8.8 22.9  5.8 12.9  4.0 42.6  6.6 24.5  5.5 39.5  5.7 70.1  31.2 73.3  9.3 61.2  22.8 69.8  16.2 26.2  7.5 184.0  71.3 0.62  0.26 42.8  7.5

46.6  11.2 22 (55%) 1.79  0.18 0.85  0.18 0.69  0.17 200.3  35.1 7.8  1.7 9.4  2.2 8.0  2.1 9.6  2.7 10.1  1.5 9.9  1.6 46.0  3.9 27.1  3.5 32.5  4.2 39.0  11.5 71.2  5.8 68.2  13.6 76.0  21.1 28.3  7.3 88.5  19.6 0.43  0.07 39.4  5.6

0.702 0.361 0.107 0.561 0.006 0.582

Left ventricular and atrial functions in hypertrophic cardiomyopathy patients with very high LVOT gradient: a speckle tracking echocardiographic study.

Determination of myocardial deformation (strain) by two-dimensional (2D) speckle tracking echocardiography (STE) is a new method for evaluating left v...
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