Speckle-Tracking Echocardiography for Detecting Subclinical Left Ventricular Dysfunction in Patients With Familial Hypercholesterolemia.

Myocardial ischemia and left ventricular dysfunction have been documented in young adults with familial hypercholesterolemia. We investigated whether speckle-tracking echocardiography can be used to detect subclinically impaired global and regional myocardial function in patients with this lipid disorder. This single-center study included 47 patients with familial hypercholesterolemia and 37 healthy control subjects who underwent transthoracic Doppler echocardiography and speckle-tracking echocardiography from January 2003 through December 2016. Conventional echocardiographic and strain parameters in the 2 groups were analyzed and compared. Left ventricular dimensions were significantly larger at end-diastole (P=0.02) and end-systole (P=0.013), left ventricular walls were significantly thicker (P <0.0001), and the early transmitral/early diastolic mitral annular velocity ratio was significantly higher (P=0.006) in the patient group than in the control group. In the patient group, global longitudinal and circumferential strain values were significantly lower (P <0.0001) and global radial strain values significantly higher (P=0.006); all segmental longitudinal strain (P <0.04) and most segmental circumferential strain values (P ≤0.01) were significantly lower; and some segmental radial strains, especially at the apex, were significantly higher (P ≤0.04). However, average longitudinal, circumferential, and radial strains in the different segments of the 3 main coronary artery territories were significantly lower in the patient group (P <0.01). Global longitudinal strain (r=0.561; P=0.001) and global circumferential strain (r=0.565; P <0.0001) were inversely correlated with low-density-lipoprotein cholesterol levels. We conclude that speckle-tracking echocardiography can be used to detect subclinical global and regional systolic abnormalities in patients with familial hypercholesterolemia.

Myocardial layer-specific analysis in patients with heterozygous familial hypercholesterolemia using speckle tracking echocardiography.

OBJECTIVE: Familial hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipid metabolism, causing premature coronary heart disease (CHD) due to accelerated atherosclerosis from birth, and the study of left ventricular (LV) function of this disease is seldom. The purpose of this study was to explore the value of layer-specific strain on assessing the early damage of LV function in asymptomatic and left ventricular ejection fraction (LVEF) well-preserved patients with heterozygous FH (HeFH). METHODS: A total of 49 patients aged 38.7±8.7 diagnosed with heterozygous familial hypercholesterolemia and who had undergone transthoracic echocardiography from 2010 to 2016 were included in this study. A total 32 healthy volunteers aged 35.6±10.3 were included as control group. Longitudinal and circumferential strains of the endocardium, myocardium, and epicardium (LSendo, LSmyo, and LSepi and CSendo, CSmyo, and CSepi) were obtained by a software enabling the analysis of strains in three myocardial layers. RESULTS: In longitudinal strain (LS), the LS of endocardium (LSendo) and the LS of myocardium (LSmyo) are significantly reduced in patients with HeFH (P<.001 in both). In circumferential strain (CS), only the CS of endocardium (CSendo) is significantly reduced (P<.001). The degree of reduction in strain is positively correlated with the TC and LDLC. CONCLUSIONS: Layer-specific evaluation of the left ventricle has great value in evaluating early impairment of LV in patients with FH. And this relatively novel technique may made it possible to help us understand the process of LV impairment in patients with FH better, thus preventing further damage.

Layer-specific myocardial strain analysis: investigation of regional deformation in a rabbit model of diabetes mellitus during different stages.

AIM: The purpose of the present study was to determine the characteristics of myocardial damage at different stages of diabetes mellitus (DM) using layer-specific myocardial strain. MATERIAL AND METHODS: Thirty six New Zealand white rabbits were randomly divided into either the control group (n =18) or the DM group (induced with alloxan) (n=18). For the myocardial deformation studies echocardiography and layer-specific strain were performed at baseline and after 3, 6, and 9 months in all of the rabbits. Three-layer longitudinal strain (LS) was calculated in the apical 4-chamber view, and three-layer circumferential strain (CS) in the short-axis view at the level of mitral valve. Layer-specific longitudinal and circumferential strains were assessed from endocardium, mid-myocardium and epicardium. For histomorphological study of the heart structure, the rabbits were sacrificed at 3, 6 and 9 months. Routine hematoxylin and eosin staining was performed. RESULTS: The highest absolute values of left ventricular longitudinal strain (LS) and circumferential strain (CS) were registered in the endocardium and the lowest in the epicardium in both groups. At 3 months, there was no significant difference in three-layer LS and CS (p>0.05), but at 6 months the LS of endocardium (LSendo) and CS of endocardium (CSendo) were lower in the DM group compared with the control group; at 9 months, the rest of the parameters were also decreased (p<0.05). Moreover, in ROC analysis at 6 months LSendo yielded better sensitivity and specificity in the detection of diabetic cardiomyopathy (AUC of LSendo was 0.897 and AUC of CSendo was 0.617). With the progression of untreated diabetes, the histopathological abnormalities intensified gradually beginning at 6 months. CONCLUSION: The progressive impairments in LV myocardial deformation and structure occurs early in diabetic rabbits, the myocardial damage may be nontransmural, and endocardial function is more susceptible to be affected by DM. Layer-specific myocardial strain echocardiography may identify subtle myocardial dysfunction in the early stages of DM.

Diagnostic Value of Transthoracic Echocardiography in Patients With Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary abnormality associated with early infant mortality and sudden death in adults. Transthoracic echocardiography (TTE) plays an important role in early detection and diagnosis of ALCAPA as a noninvasive modality. However, its diagnostic value is not well studied. The purpose of this study is to determine the performance of TTE in the diagnostic assessment of ALCAPA as compared with coronary CT and invasive coronary angiography. A total of 22 patients (13 women and 9 men, mean age, 12.9 ±â€Š19.5 years) with ALCAPA who underwent echocardiographic examination for clinical diagnosis were retrospectively reviewed and analyzed. Transthoracic echocardiographic features of ALCAPA were analyzed and its diagnostic value was compared with invasive coronary angiography and coronary CT angiography (CTA) with surgical findings serving as the gold standard. Surgery was performed in all of the patients to establish the dual coronary artery system. Five underwent the Takeuchi procedure and 17 had re-implantation of the anomalous left coronary artery. Of 20 patients, echocardiographic diagnoses were in good agreement with findings at surgery, resulting in the diagnostic accuracy of 90.9%. Two cases were misdiagnosed-one as the right coronary artery to pulmonary artery fistula and the other as rheumatic heart disease. The echocardiographic features of these patients with ALCAPA included: abnormal left coronary ostium arising from the pulmonary trunk with retrograde coronary artery flow in 20 patients; enlargement of the right coronary artery in 17 patients; abundant intercoronary septal collaterals in 17 patients; and moderate and significant mitral regurgitation in 14 patients. The diagnostic accuracy of invasive coronary angiography (in 17 patients) and coronary CTA (in 9 patients) was 100%. This study shows that TTE is an accurate, noninvasive imaging modality for displaying the origin of coronary arteries and demonstrating the coronary courses as well as other associated abnormalities in patients with ALCAPA.

Suppressed expression of mitogen-activated protein kinases in hyperthermia induced defective neural tube.

Neural tube defects (NTDs) are common congenital malformations. Mitogen-activated protein kinases (MAPKs) pathway is involved in many physiological processes. HMGB1 has been showed closely associated with neurulation and NTDs induced by hyperthermia and could activate MAPKs pathway. Since hyperthermia caused increased activation of MAPKs in many systems, the present study aims to investigate whether HMGB1 contributes to hyperthermia induced NTDs through MAPKs pathway. The mRNA levels of MAPKs and HMGB1 between embryonic day 8.5 and 10 (E8.5-10) in hyperthermia induced defective neural tube were detected by real-time quantitative polymerase chain reaction (qPCR). By immunofluorescence and western blotting, the expressions of HMGB1 and phosphorylated MAPKs (ERK1/2, JNK and p38) in neural tubes after hyperthermia were studied. The mRNA levels of MAPKs and HMGB1, as well as the expressions of HMGB1 along with phosphorylated JNK, p38 and ERK, were downregulated in NTDs groups induced by hyperthermia compared with control. The findings suggested that HMGB1 may contribute to hyperthermia induced NTDs formation through decreased cell proliferation due to inhibited phosphorylated ERK1/2 MAPK.

HMGB1 enhances embryonic neural stem cell proliferation by activating the MAPK signaling pathway.

Neural stem cells (NSCs) are involved in neural tube formation. As the high-mobility group box 1 (HMGB1) protein is involved in neurulation and is present at elevated levels in neural tube defects (NTDs) induced by hyperthermia, we have now investigated the effects of HMGB1 on proliferation, differentiation, and MAPK signaling pathways of NSCs in vitro. We constructed a lentivirus vector with HMGB1 siRNA and used it to infect NSCs. Down-regulation of HMGB1 expression was confirmed. Proliferation of NSCs was determined by MTS and nestin/BrdU double-labeling. Differentiation of NSCs was assessed using ß-tubulinIII and GFAP. Knockdown of HMGB1 significantly suppressed NSC proliferation but hardly affected differentiation, which was regulated by decreased expression of MAPK signaling pathways. Thus, HMGB1 has beneficial effects on neurulation and may serve as a new target for the prevention of NTDs.