Reduced Myocardial Reserve in Young X-Linked Muscular Dystrophy Mice Diagnosed by Two-Dimensional Strain Analysis Combined with Stress Echocardiography

Abstract

Background Early, sensitive and reproducible evaluation of left ventricular (LV) function is imperative for diagnosis of cardiac dysfunction in Duchene muscular dystrophy (DMD) patients. We hypothesized that combining 2D-strain analysis with catecholamine stress could be a sensitive method for detecting early cardiac dysfunction. Methods mdx (C57BL/10ScSn-Dmdmdx/J, a mouse model of DMD) and control (C57BL/10ScSn) mice were studied with conventional M-mode and high frequency ultrasound based 2D speckle tracking echocardiography (STE)using long- and short-axis images of LV at baseline and after isoprenaline (2μg/g BW, i.p.). Results Conventional M-mode analysis showed no differences in LV fractional shortening, wall thickness or internal diameter at diastole between mdx and control mice before the age of 6 months. Isoprenaline increased LV ejection fraction and fractional shortening to the same extent in mdx and control mice at young ages (3, 4 and 5 months). No differences in basal peak systolic strain (PSS) but increased standard deviations of times to PSS between young mdx and control mice were found. After isoprenaline, PSS and percentile changes of PSS were significantly diminished in mdx mice compared to control mice at young ages. Isoprenaline increased normalized maximum difference of times to PSS in young mdx mice but not in young control mice, suggesting isoprenaline reduces cardiac contractile synchrony in young mdx mice. Conclusions Our study suggests that catecholamine stress coupled with 2D strain analysis is a feasible and sensitive approach for detecting early onset of cardiac dysfunction, which is instrumental for early diagnosis of cardiac dysfunction and early treatment.

Cardiac Protection after Systemic Transplant of Dystrophin Expressing Chimeric (DEC) Cells to the mdx Mouse Model of Duchenne Muscular Dystrophy

“…Initiating antifibrotic therapies before the development of overt LV systolic dysfunction may be helpful in delaying DMD related cardiac dysfunction, so coupling DEC therapy treatments with angiotensin-converting enzyme inhibitors, aldosterone antagonists, or angiotensin receptor blockers should also be investigated in mdx mice also be called for [11,13,14]. Analysis with imaging designed to quantify myocardial fibrosis with echocardiographic measurements or with late gadolinium enhancement studies in addition to histopathology is also warranted within such studies [9,10,52,55].…”

“…The left ventricular dimensions (end-diastolic diameter and end-systolic diameter, denoted as LVEDD and LVESD, respectively), left ventricular volume (end-diastolic volume and end-systolic volume, denoted as LVEDV and LVESV, respectively) and heart rate (HR) were measured from 4.95 s cine images acquired from M-Mode tracings. From these measurements, stroke volume, ejection fraction, fractional shortening and cardiac output were calculated using instructions outlined from the American Society of Echocardiography [9,10,13,43,51,52].…”

Capabilities and Limitations of Speckle Tracking Stress Echocardiography

“…Технология спекл-трекинг стресс-эхокардиографии потенциально может быть прогностически значимой в оценке функции миокарда при различных заболеваниях сердечно-сосудистой системы, а также при некардиогенных заболеваниях. Большое количество опубликованных исследований обеспечивают доказательную базу для потенциального применения этой технологии в различных клинических ситуациях [10][11][12][13][14][15]. Однако технология спекл-трекинг при стресс-эхокардиографии до сих пор не рекомендована для рутинного применения у большинства пациентов.…”

“…В рекомендациях Американского общества эхокардиографии и Европейского общества сердечно-сосудистой визуализации указывается, что параметр глобальной продольной деформации ЛЖ является воспроизводимым и применимым в оценке систолической функции миокарда ЛЖ в состоянии покоя [3]. Достаточно большое количество исследований демонстрируют, что применение технологии спекл-трекинг в анализе результатов стресс-эхокардиографии позволяет дать количественную оценку как глобальной деформации миокарда ЛЖ, так и деформации каждого сегмента миокарда ЛЖ [10][11][12][13][14]. В связи с этим, а также с появлением более совершенных эхокардиографических ультразвуковых систем технология спеклтрекинг широко используется как в эхокардиографии в покое, так и при стресс-эхокардиографии.…”

Usefulness of speckle-tracking echocardiography for early detection in children with Duchenne muscular dystrophy: a meta-analysis and trial sequential analysis

“…Previous animal studies have usually used echocardiography to assess cardiac function. They revealed that some strain parameters were significantly changed in the DMD dog/mouse model and that strain analysis using speckle-tracking echocardiography (STE) is a feasible and sensitive approach for detecting cardiac dysfunction [ 7 , 8 ]. STE can quantify myocardial strain and detect subclinical left ventricular dysfunction before left ventricular ejection fraction (LVEF) begins decreasing [ 9 ].…”