Decreased diastolic wall strain is associated with adverse left ventricular remodeling even in patients with normal left ventricular diastolic function

Min-Kyung Kang 0 Sungbae Ju 0 Hee-Sun Mun 0 Seonghoon Choi 0 Jung Rae Cho 0 Namho Lee 0 0 M.-K. Kang (&) S. Ju H.-S. Mun S. Choi J. R. Cho N. Lee Cardiology Division, Kangnam Sacred Heart Hospital, Hallym University Medical Center , Seoul , South Korea Background The pathophysiology of diastolic dysfunction is complex, but can be simply described as impaired LV myocardial relaxation and/or increased LV stiffness. The objective of this study is to clarify true normal left ventricular (LV) diastolic function and early stage of diastolic dysfunction before relaxation abnormality develops in patients with normal LV diastolic function using simple diastolic wall strain (DWS) in South Korea. Methods DWS which is a non-invasive, load-independent, and reproducible estimator of LV stiffness using twodimensional echocardiography using the difference between posterior wall thickness in systole and diastole to approximate LV stiffness. A total of 349 consecutive patients with normal LV diastolic function by echocardiography were enrolled. According to DWS, patients were divided into two groups: high DWS (Cmedian 175) vs. low DWS (\median 174). Results Patients with low DWS were more obese and showed higher blood pressure, and had more prevalent hypertension and hyperlipidemia. In addition, those with low DWS had higher LV end-systolic volume, LV mass index, E/E' and lower ejection fraction and E' velocity. Among them, higher LVESV and LVMI were independently associated with low DWS. Conclusions These data suggests that simple DWS might be helpful in identifying a subgroup of subtle diastolic dysfunction. Our data suggest that early change of diastolic dysfunction might start with abnormal LV geographic changes preceding functional changes. - Left ventricular (LV) diastolic dysfunction is common in the general population, and is associated with incident heart failure and increased mortality [1, 2]. The pathophysiology of diastolic dysfunction is complex, but can be simply described as impaired LV myocardial relaxation and/or increased LV stiffness, both of which can lead to increased LV filling pressures at rest or with exercise [3]. In contrast to asymptomatic diastolic dysfunction, sometimes we encounter unexpected normal LV diastolic patterns in older patients concomitant with hypertension, diabetes, or coronary artery disease. However, even if they met the criteria for normal LV diastolic function, their LV diastolic function might not be the same as true normal LV diastolic function of young healthy subjects. Recently, a non-invasive, load-independent, and reproducible estimator of LV stiffness using M-mode echocardiography, namely diastolic wall strain (DWS), has been proposed [4, 5]. DWS, an extension of linear elastic theory, uses the difference between posterior wall thickness in systole (PWTs) and diastole (PWTd) to approximate LV stiffness, which decreased wall thinning during diastole reflects reduced LV compliance and distensibility, and thus, increased LV stiffness [4]. DWS correlated well with the diastolic stiffness constant measured invasively in an animal model [4]. Clinically, DWS is also useful in assessing diastolic stiffness, and more advanced diastolic stiffness is associated with worse outcomes in heart failure with preserved ejection fraction (HFpEF) [5]. Recently, Takagi et al. [6] reported that low DWS is associated with raised postexercise E/E ratio in elderly patients without obvious myocardial ischemia and patients with low DWS are likely to develop raised E/E after exercise. Therefore, the objective of this study was to determine the relationship between DWS and cardiac structure and function, and to see whether increased diastolic stiffness as assessed by DWS is a predictive value for subtle diastolic dysfunction or clinical implications even in patients with normal LV diastolic function. If there were any differences, it might be helpful to distinguish subtle diastolic dysfunction in patients who have predisposing factors for diastolic dysfunction from true normal diastolic function. Study design and participants We conducted an observational cross-sectional study in which we enrolled 349 patients who met the criteria for normal LV diastolic function among 6,277 subjects who underwent transthoracic echocardiography at Kangnam Sacred Heart Hospital between April 2012 to May 2013 [40 12 years, 153 (44 %) women]. We enrolled patients who met criteria for normal LV diastolic function as both E/A, E/A ratio were 1.1 or higher, deceleration time (DT) was 142220 ms, and septal E velocity was 10 cm/s or higher [7], and patients with overt heart diseases [severe valvular diseases, systolic heart failure (HF), or pericardial diseases], LV ejection fraction (EF) B50 %, E/E C15, or age C80 were excluded from the study. On 140 patients, carotid ultrasound was performed, and among them, 72 patients underwent also brachial-ankle pulse wave velocity (baPWV). We also collected participant data on demographic, anthropometric, and inflammatory parameters. Transthoracic echocardiography (TTE) TTE was performed using standard techniques with a 2.5MHz transducer. The standard 2-D and Doppler echocardiography was performed using a commercially available echocardiographic machine (Vivid 7R GE Medical System, Horten, Norway). LV end-diastolic dimensions (LVEDD), end-diastolic interventricular septal thickness (IVSTd), and end-diastolic left ventricular posterior wall thickness (PWTd) were measured at end-diastole according to the standards established by the American Society of Echocardiography [8]. LV EF was determined by the biplane Simpsons method [9]. Maximal LA volume was calculated using the Simpson method [10] and indexed to the body surface area (LA volume index; LAVI). Left ventricular mass (LVM) was calculated using the Devereux formula [11]: LVM = 1.04[(LVEDD ? IVSTd ? PWTd)3 - (LVEDD)3] - 13.6. Thereafter, the LV mass index (LVMI) was calculated and indexed to body surface area, and LV hypertrophy was defined by an LV mass index [95 g/m2 in women or [115 g/m2 in men. Calculation of relative wall thickness (RWT) by the formula 29 (PWTd)/LVEDD permits categorization of an increase in LV mass as either concentric (RWT [0.42) or eccentric (RWT B0.42) hypertrophy and allows identification of concentric remodeling (normal LV mass with increased RWT) [8]. Volumes were obtained using biplane Simpsons rule from the apical 4- and 2-chamber views. The endocardial border was manually traced by an experienced sonographer according to the recommendations of the American Society of Echocardiography, leaving the papillary muscles and trabeculations within the cavity [12]. Measurements of LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and EF were obtained offline, with LVEDV measurements at the frame just prior to mitral valve closure and LVESV measured on the image with the smallest LV cavity. Additionally in the apical 4-chamber view the ventricular (...truncated)