Global longitudinal strain assessment in contrast-enhanced echocardiography in breast cancer patients: a feasibility study.

BACKGROUND: Left ventricular global longitudinal strain (GLS) obtained from two-dimensional speckle-tracking echocardiography (2D-STE) can reflect cancer therapy-related cardiac dysfunction in breast cancer (BC) patients, however, the accuracy and reproducibility of 2D-STE are restricted due to poor image quality. METHODS: Between January 2019 and October 2021, 160 consecutive BC patients aged ≥ 18 years were recruited. The 160 BC patients (mean age: 48.41 ± 9.93 years, 100% women) underwent both 2D-STE and Contrast-enhanced echocardiography (CEcho), 125 of whom were included in the measurement of GLS. The intraclass correlation coefficient (ICC) was used to determine the intra- and inter-observer reproducibility of 2D-STE and CEcho-STE. Correlation (r) was calculated using Pearson correlation. Statistical significance was set at P < 0.05. RESULTS: Among 160 BC patients, more segments were recognized by CEcho-STE than by 2D-STE (2,771, 99.53% vs. 2,440, 84.72%). The left ventricular ejection fraction (LVEF) obtained by 2D was lower than CEcho (61.75 ± 6.59% vs. 64.14 ± 5.97%, P < 0.0001). The GLS obtained by 2D-STE was lower than CEcho-STE (-21.74 ± 2.77% vs. -26.79 ± 4.30%, P = 0.001). The ICC of the intraobserver and interobserver agreements in the CEcho-STE group was lower than that in the 2D-STE group. GLS measurements were in good agreement between the 2D-STE and CEcho-STE groups (r = 0.773). CONCLUSIONS: CEcho can overcome some imaging limitations and recognize more segments than 2D, which may provide an LVEF and GLS closer to the true value. Based on AutoStrain, CEcho-STE may serve as a complementary method for those with poor image quality.

Free fatty acid can induce cardiac dysfunction and alter insulin signaling pathways in the heart.

BACKGROUND: Insulin resistance has been independently related to heart failure. However, the specific mechanisms of high FFA levels in the pathophysiology of heart failure in insulin-resistant states are remain largely unclear. This study investigated whether elevated circulating free fatty acids (FFA) levels result in impaired cardiac structure and function in vivo via insulin-related signaling pathways in myocardium. METHODS: Male Wistar rats were randomly divided into the intralipid group (20% intralipid plus heparin infusion) and the control group (glycerol infusion). Blood samples were collected before and after 6-, 12-, and 24-h infusions. Cardiac structure and function were measured using echocardiography. Maximum velocity of myocardial contraction (+dP/dt max) and diastole (-dP/dt max) were measured using a physiological polygraph in vivo. Heart tissues were collected for western blotting. RESULTS: Compared with the control group, plasma FFA, plasma glucose, and serum insulin levels increased significantly in the intralipid group. With increasing infusion time, cardiac function in the intralipid group decreased gradually compared with the control group. After a 24-h infusion, early (E', cm/s) diastolic peak velocities and (-dP/dt max) decreased significantly. Protein expression of phosphatidylinositol 3-kinase (PI3K), the serine/threonine kinase Akt, and phosphorylated Akt in myocardium increased after a 6-h infusion and decreased significantly after a 24-h infusion in the intralipid group. Protein expression of glucose transporter type 4 (GLUT4), Adenosine 5'-monophosphate -activated protein kinase (AMPK), phosphorylated AMPK(p-AMPK), and endothelial nitric oxide synthase (eNOS) in myocardium gradually decreased in the intralipid group. CONCLUSIONS: Elevated FFA levels may impair cardiac function and cardiac dysfunction might result from myocardial insulin resistance with significant changes to PI3K-Akt-GLUT4 and AMPK-eNOS signaling pathways with increasing FFA levels.

Left Atrial Appendage Parameters Assessed by Real-Time Three-Dimensional Transesophageal Echocardiography Predict Thromboembolic Risk in Patients With Nonvalvular Atrial Fibrillation.

OBJECTIVES: In nonvalvular atrial fibrillation (NVAF) patients, the effect of left atrial appendage (LAA) morphology, structure, and hemodynamic characteristics evaluated by real-time 3D transesophageal echocardiography (RT3D-TEE) on thromboembolic risk has not been elucidated. METHODS: A total of 444 NVAF patients who underwent clinically indicated RT3D-TEE were enrolled in the study. The orifice size, orifice area, depth, and volume measurements of the LAA were assessed using Philips QLAB 9.0. The LAA characteristics were compared among different CHA2 DS2 -VASc thromboembolic risk subgroups, as well as between the thromboembolic event and nonevent groups. RESULTS: The orifice size, orifice area, and end-diastolic volumes of the LAA were increased with an increasing CHA2 DS2 -VASc risk score in the NVAF patients, whereas the emptying rate was decreased. The NVAF patients with LAA thrombus exhibited a significantly increased end-diastolic volume (7.39 ± 3.47 versus 5.21 ± 2.59 mL, P = .003) and higher prevalence of the cauliflower shaped LAA (64.3% versus 25%, P = .004) compared with those without thrombus. Logistic regression indicated that the LAA end-diastolic volume (P = .002; odds ratio 1.556; 95% confidence interval 1.176-2.057) and cauliflower shape (P = .001; odds ratio, 10.177; 95% confidence interval, 2.458-42.140) were independent predictors of thromboembolic events in patients with NVAF following adjustment for the CHA2 DS2 -VASc score. CONCLUSIONS: The LAA end-diastolic volume and cauliflower phenotype predict thromboembolic events independent of the CHA2 DS2 -VASc score, and these data improve stroke prediction in NVAF patients.

[Preliminary Study of Necroptosis in Cardiac Hypertrophy Induced by Pressure Overload].

The aim of this study was to observe whether necroptosis is involved in the process of cardiac hypertrophy induced by pressure overload. SD rats underwent transverse abdominal aortic constriction (TAC) operation for establishing cardiac hypertrophy model. The structure and function of the left ventricle of rats were evaluated via echocardiography, left ventricular mass index, the expression of markers of cardiac hypertrophy and histological detection. Real-time PCR and Western blot were used to measure the gene and protein expression of receptor interacting protein kinase 1 and 3 (RIPK1 and RIPK3, the necroptosis markers) respectively. Four weeks after TAC operation, rat model for cardiac hypertrophy was established. The experimental data showed that the gene and protein expressions of RIPK1 and RIPK3 in the rat heart hypertrophic tissues after TAC for 4 weeks were increased significantly compared with those in the sham group. HE staining showed cardiomyocytes injury and hypertrophy in the hearts of TAC rat models. By transmission electron microscope, we observed that mitochondria of cardiomyocytes were damaged seriously in the TAC models. Treatment with losartan used, the selective antagonist of angiotensin II type I receptor could improve the cardiac function of TAC rats. Moreover, losartan treatment decreased the expression of RIPK1 and RIPK3 in heart tissues of TAC rats. The results suggest that necroptosis occurrs in the process of cardiac hypertrophy with pressure overload, and losartan could alleviate the cardiac hypertrophy and inhibit necroptosis.

Global longitudinal strain at 3 months after therapy can predict late cardiotoxicity in breast cancer.

BACKGROUND: Cancer therapy-related cardiovascular toxicity (CTR-CVT) is a major contributor to poor prognosis in breast cancer (BC) patients undergoing chemotherapy. Left ventricular global longitudinal strain (LV GLS) has predictive value for CTR-CVT, while few researchers take into account late-onset CTR-CVT. This study sought to provide a guide for the prediction of late-onset CTR-CVT in primary BC over the 2 years follow-up via strain and contrast-enhanced echocardiography. METHODS: Anthracycline and anthracycline + targeted medication groups were created from 111 patients with stage I-III primary BC who were prospectively included. The left ventricular diastolic function, LV global long-axis strain (GLS); left ventricular ejection fraction by contrast-enhanced echocardiography (c-LVEF), and electrocardiograms were collected at baseline, 3, 6, 12, and 24 months after the start of cancer treatment. The high-sensitivity troponin-T and NT-pro BNP at baseline and 3 months after chemotherapy were measured. RESULTS: (1) LV GLS decreased in BC patients over time. (2) After 12 months' follow-up, the LV GLS in the anthracycline+ targeted group was lower than in the anthracycline group. After 24 months' follow-up, the GLS and c-LVEF in the anthracycline + targeted group declined while the E/e' increased. (3) Decreased LVEF (56%) and arrhythmia (38%) are the common causes of CTR-CVT. Lower LVEF was a major factor in late-onset CTR-CVT. (4) Combination of LV GLS and c-LVEF at 3 months were used as predictors for CTR-CVT and exhibited a higher AUC than either one alone (AUC = 0.929, 95% CI: 0.863-0.970). LV GLS at 3 months can predict the late-onset CTR-CVT (AUC = 0.745, p < 0.001), and the cut-off is 20.32%. CONCLUSIONS: As time went on, the systolic and diastolic dysfunction of BC patients get worsened. The combination of LV GLS and c-LVEF is better in the prediction of CTR-CVT. Only the LV GLS at 3 months can predict the late-onset CTR-CVT.