Left Atrial Phasic Function Impairment in Subacute and Chronic Pulmonary Embolism Patients With Different Degrees of Obstruction: An MRI Feature Tracking Study.

BACKGROUND: The alteration of left atrial (LA) phasic function in subacute and chronic pulmonary embolism (PE) patients is unclear. PURPOSE: To investigate LA phasic strain and LA-right ventricular (RV) interaction in subacute and chronic PE patients with different degrees of obstruction by MRI-feature tracking (MRI-FT). STUDY TYPE: Retrospective. POPULATION: One hundred three PE patients (54 subacute [2 weeks to 3 months after initial symptoms], 49 chronic [>3 months after initial symptoms]) and 80 controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady state free precession sequence. ASSESSMENT: Patients were divided into mild (pulmonary artery obstruction index [PAOI] < 30%, N = 57), moderate (30% ≤ PAOI < 50%, N = 27), and severe (50% ≥ PAOI, N = 19) PE subgroups. LA reservoir, conduit, and active pump longitudinal strains (εs, εe, and εa) and strain rates (SRs, SRe, and SRa) and biventricular global strains were measured. Determinants of LA strains were investigated. STATISTICAL TESTS: ANOVA, t-tests, Mann-Whitney U tests, linear regression. P < 0.05 was considered statistically significant. RESULTS: For both subacute and chronic PE patients, LA reservoir, conduit, and active pump strains and strain rates were significantly lower than in controls. However, there were no significant differences in LA strains between patients with subacute and chronic PE (P = 0.933, 0.625, and 0.630 for εs, εe, and εa). The severe PE subgroup had significantly higher εa and SRa than the mild and moderate PE subgroups. LA strains were significantly correlated with RV diameter and biventricular strains, and RV diameter (ß = -6.836, -4.084, and -1.899 for εs, εe, and εa) was independently associated with LA strains after adjustment for other factors (R2 = 0.627, 0.536, and 0.437 for εs, εe, and εa). DATA CONCLUSION: LA phasic function evaluated by MRI-FT was significantly impaired in subacute and chronic PE patients, and LA active pump function in the severe PE subgroup was higher than that in the mild and moderate PE subgroups. The independent association between RV diameter and LA strains demonstrates that RV diameter may be an important indicator for monitoring LA dysfunction in PE patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Assessment of subclinical LV myocardial dysfunction in T2DM patients with diabetic peripheral neuropathy: a cardiovascular magnetic resonance study.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, and has been demonstrated to be independently associated with cardiovascular events and mortality. This aim of this study was to investigate the subclinical left ventricular (LV) myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients with and without DPN. METHODS: One hundred and thirty T2DM patients without DPN, 61 patients with DPN and 65 age and sex-matched controls who underwent cardiovascular magnetic resonance (CMR) imaging were included, all subjects had no symptoms of heart failure and LV ejection fraction ≥ 50%. LV myocardial non-infarct late gadolinium enhancement (LGE) was determined. LV global strains, including radial, circumferential and longitudinal peak strain (PS) and peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were evaluated using CMR feature tracking and compared among the three groups. Multivariable linear regression analyses were performed to determine the independent factors of reduced LV global myocardial strains in T2DM patients. RESULTS: The prevalence of non-infarct LGE was higher in patients with DPN than those without DPN (37.7% vs. 19.2%, p = 0.008). The LV radial and longitudinal PS (radial: 36.60 ± 7.24% vs. 33.57 ± 7.30% vs. 30.72 ± 8.68%; longitudinal: - 15.03 ± 2.52% vs. - 13.39 ± 2.48% vs. - 11.89 ± 3.02%), as well as longitudinal PDSR [0.89 (0.76, 1.05) 1/s vs. 0.80 (0.71, 0.93) 1/s vs. 0.77 (0.63, 0.87) 1/s] were decreased significantly from controls through T2DM patients without DPN to patients with DPN (all p < 0.001). LV radial and circumferential PDSR, as well as circumferential PS were reduced in both patient groups (all p < 0.05), but were not different between the two groups (all p > 0.05). Radial and longitudinal PSSR were decreased in patients with DPN (p = 0.006 and 0.003, respectively) but preserved in those without DPN (all p > 0.05). Multivariable linear regression analyses adjusting for confounders demonstrated that DPN was independently associated with LV radial and longitudinal PS (ß = - 3.025 and 1.187, p = 0.014 and 0.003, respectively) and PDSR (ß = 0.283 and - 0.086, p = 0.016 and 0.001, respectively), as well as radial PSSR (ß = - 0.266, p = 0.007). CONCLUSIONS: There was more severe subclinical LV dysfunction in T2DM patients complicated with DPN than those without DPN, suggesting further prospective study with more active intervention in this cohort of patients.

Impact of Functional Mitral Regurgitation on Left Ventricular Strain in Nonischemic Dilated Cardiomyopathy Patients with Type 2 Mellitus Diabetes: A Magnetic Resonance Feature Tracking Study.

BACKGROUND: The impact of functional mitral regurgitation and type 2 mellitus diabetes (T2DM) on left ventricular (LV) strain in nonischemic dilated cardiomyopathy (NIDCM) patients remains unclear. PURPOSE: To evaluate the impact of mitral regurgitation severity on LV strain, and explore additive effect of T2DM on LV function across varying mitral regurgitation severity levels in NIDCM patients. STUDY TYPE: Retrospective. POPULATION: 352 NIDCM (T2DM-) patients (49.1 ± 14.6 years, 67% male) (207, 85, and 60 no/mild, moderate, and severe mitral regurgitation) and 96 NIDCM (T2DM+) patients (55.2 ± 12.4 years, 77% male) (47, 30, and 19 no/mild, moderate, and severe mitral regurgitation). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence. ASSESSMENT: LV geometric parameters and strain were measured and compared among groups. Determinants of LV strain were investigated. STATISTICAL TEST: Student's t-test, Mann-Whitney U test, one-way ANOVA, Kruskal-Wallis test, univariable and multivariable linear regression. P < 0.05 was considered statistically significant. RESULTS: LV GLPS and longitudinal PDSR decreased gradually with increasing mitral regurgitation severity in NIDCM patients with T2DM(GLPS: -5.7% ± 2.1% vs. -4.3% ± 1.6% vs. -2.6% ± 1.3%; longitudinal PDSR:0.5 ± 0.2 sec-1 vs. 0.4 ± 0.2 sec-1 vs. 0.3 ± 0.1 sec-1). NIDCM (T2DM+) demonstrated decreased GCPS and GLPS in the no/mild subgroup, reduced LV GCPS, GLPS, and longitudinal PDSR in the moderate subgroup, and reduced GRPS, GCPS, GLPS, and longitudinal PDSR in the severe subgroup compared with NIDCM (T2DM-) patients. Multivariable regression analysis identified that mitral regurgitation severity (ß = -0.13, 0.15, and 0.25 for GRPS, GCPS, and GLPS) and the presence of T2DM (ß = 0.14 and 0.13 for GCPS and GLPS) were independent determinants of LV strains in NIDCM patients. DATA CONCLUSION: Increased mitral regurgitation severity is associated with reduced LV strains in NIDCM patients with T2DM. The presence of T2DM exacerbated the decline of LV function across various mitral regurgitation levels in NIDCM patients, resulting in reduced LV strains. TECHNICAL EFFICACY: Stage 3.

Impact of Type 2 Diabetes Mellitus on Left Atrioventricular Coupling and Left Atrial Deformation in Patients with Essential Hypertension: An MRI Feature Tracking Study.

BACKGROUND: Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are both associated with left ventricular (LV) and left atrial (LA) structural and functional abnormalities; however, the relationship between the left atrium and ventricle in this population is unclear. PURPOSE: To identify differences between hypertensive patients with and without T2DM as the basis for further investigation the atrioventricular coupling relationship. STUDY TYPE: Cross-sectional, retrospective study. POPULATION: 89 hypertensive patients without T2DM [HTN (T2DM-)] (age: 58.4 +/- 11.9 years, 48 male), 62 hypertensive patients with T2DM [HTN (T2DM+)] (age: 58.5 +/- 9.1 years, 32 male) and 70 matched controls (age: 55.0 +/- 9.6 years, 37 male). FIELD STRENGTH/SEQUENCE: 2D balanced steady-state free precession cine sequence at 3.0 T. ASSESSMENT: LA reservoir, conduit, and booster strain (εs, εe, and εa) and strain rate (SRs, SRe, and SRa), LV radial, circumferential and longitudinal peak strain (PS) and peak systolic strain rate and peak diastolic strain rate (PSSR and PDSR) were derived from LA and LV cine images and compared between groups. STATISTICAL TESTS: Chi-square or Fisher's exact test, one-way analysis of variance, analysis of covariance, Pearson's correlation, multivariable linear regression analysis, and intraclass correlation coefficient. A P value <0.05 was considered significant. RESULTS: Compared with controls, εs, εe, SRe and PS-longitudinal, PDSR-radial, and PDSR-longitudinal were significantly lower in HTN (T2DM-) group, and they were even lower in HTN (T2DM+) group than in both controls and HTN (T2DM-) group. SRs, εa, SRa, as well as PS-radial, PS-circumferential, PSSR-radial, and PSSR-circumferential were significantly lower in HTN (T2DM+) compared with controls. Multivariable regression analyses demonstrated that: T2DM and PS-circumferential and PS-longitudinal (ß = -4.026, -0.486, and -0.670, respectively) were significantly associated with εs; T2DM and PDSR-radial and PDSR-circumferential were significantly associated with εe (ß = -3.406, -3.352, and -6.290, respectively); T2DM and PDSR-radial were significantly associated with SRe (ß = 0.371 and 0.270, respectively); T2DM and PDSR-longitudinal were significantly associated with εa (ß = -1.831 and 5.215, respectively); and PDSR-longitudinal was significantly associated with SRa (ß = 1.07). DATA CONCLUSION: In hypertensive patients, there was severer LA dysfunction in those with coexisting T2DM, which may be associated with more severe LV dysfunction and suggests adverse atrioventricular coupling. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Biventricular Impairment and Ventricular Interdependence in Patients With Alcoholic Cardiomyopathy: Insights Through Cardiac Magnetic Resonance Imaging.

BACKGROUND: Alcoholic cardiomyopathy (ACM) can lead to progressive cardiac dysfunction and heart failure, but little is known about biventricular impairment and ventricular interdependence (VI) in ACM patients. PURPOSE: To use cardiac MRI to investigate biventricular impairment and VI in ACM patients. STUDY TYPE: Retrospective. POPULATION: Forty-one male patients with ACM and 45 sex- and age-matched controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence, inversion recovery prepared echo-planar imaging sequence and phase-sensitive inversion recovery sequence. ASSESSMENT: Biventricular structure, function, and global strain (encompassing peak strain [PS], peak systolic, and diastolic strain rate), PS of interventricular septal (IVS), microvascular perfusion (including upslope and time to maximum signal intensity [TTM]), late gadolinium enhancement (LGE), and baseline characteristics were compared between the controls and ACM patients. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, Pearson's correlation, and multivariable linear regression models with a stepwise selection procedure. A two-tailed P value <0.05 was deemed as statistically significant. RESULTS: Compared to control subjects, ACM patients showed significantly biventricular adverse remodeling, reduced left ventricle (LV) global upslope and prolonged global TTM, and the presence of LGE. ACM patients were characterized by a significant decline in all global strain within the LV, right ventricle (RV), and IVS compared with the controls. RV global PS was significantly associated with LV global PS and IVS PS in radial, circumferential, and longitudinal directions. Multivariable analyses demonstrated the longitudinal PS of IVS was significantly correlated with RV global radial PS (ß = 0.614) and circumferential PS (ß = 0.545). Additionally, RV global longitudinal PS (GLPS) was significantly associated with radial PS of IVS (ß = -0.631) and LV GLPS (ß = 1.096). DATA CONCLUSION: ACM patients exhibited biventricular adverse structural alterations and impaired systolic and diastolic function. This cohort also showed reduced LV microvascular perfusion, the presence of LGE, and unfavorable VI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

H3K4 Trimethylation Mediate Hyperhomocysteinemia Induced Neurodegeneration via Suppressing Histone Acetylation by ANP32A.

Homocysteine (Hcy) is an independent and serious risk factor for dementia, including Alzheimer's disease (AD), but the precise mechanisms are still poorly understood. In the current study, we observed that the permissive histone mark trimethyl histone H3 lysine 4 (H3K4me3) and its methyltransferase KMT2B were significantly elevated in hyperhomocysteinemia (HHcy) rats, with impairment of synaptic plasticity and cognitive function. Further research found that histone methylation inhibited synapse-associated protein expression, by suppressing histone acetylation. Inhibiting H3K4me3 by downregulating KMT2B could effectively restore Hcy-inhibited H3K14ace in N2a cells. Moreover, chromatin immunoprecipitation revealed that Hcy-induced H3K4me3 resulted in ANP32A mRNA and protein overexpression in the hippocampus, which was regulated by increased transcription Factor c-fos and inhibited histone acetylation and synapse-associated protein expression, and downregulating ANP32A could reverse these changes in Hcy-treated N2a cells. Additionally, the knockdown of KMT2B restored histone acetylation and synapse-associated proteins in Hcy-treated primary hippocampal neurons. These data have revealed a novel crosstalk mechanism between KMT2B-H3K4me3-ANP32A-H3K14ace, shedding light on its role in Hcy-related neurogenerative disorders.

Effect of concomitant atrial septal defect on left ventricular function in adult patients with unrepaired Ebstein's anomaly: a cardiovascular magnetic resonance imaging study.

BACKGROUND: Due to the heterogeneity of anatomic anomalies in Ebstein's anomaly (EA), particularly in the subset of patients with atrial septal defect (ASD), hemodynamic changes, which ultimately cause left ventricular (LV) deterioration remain unclear. The current study aimed to investigate the effect of concomitant ASD on LV function using cardiovascular magnetic resonance (CMR) imaging in patients with EA. METHODS: This study included 31 EA patients with ASD, 76 EA patients without ASD, 35 patients with simple ASD and 40 healthy controls. Left/right ventricular (RV, the RV was defined as a summation of the functional RV and atrialized RV in EA patients) volumes and functional parameters, LV strain parameters, and echocardiogram indices were compared among the four groups. Associations between variables were evaluated via Spearman or Pearson correlation analyses. The association between risk factors and LV ejection fraction (EF) was determined via multivariate linear regression analysis. RESULTS: Both EA patients and ASD patients had a higher RV/LV end-diastolic volume (RVEDV/LVEDV) as well as lower LV and RV ejection fractions (LVEF/RVEF) compared to healthy controls (all p < 0.05). Moreover, the EA patients with ASD had a significantly higher RVEDV/LVEDV and a lower LVEF and RVEF than those without ASD (all p < 0.05). Multivariate linear regression analysis revealed that the presence of ASD was independently associated with LVEF (ß = - 0.337, p < 0.001). The RVEDV/LVEDV index was associated with LVEF (r = - 0.361, p < 0.001). Furthermore, the LV longitudinal peak diastolic strain rate (PDSR) was lower in EA patients with ASD than those without ASD, patients with simple ASD, and healthy controls (p < 0.05). CONCLUSION: Concomitant ASD is an important risk factor of LV dysfunction in patients with EA, and diastolic dysfunction is likely the predominate mechanism related to LV dysfunction.

Subclinical left ventricular deformation and microvascular dysfunction in T2DM patients with and without peripheral neuropathy: assessed by 3.0 T cardiac magnetic resonance imaging.

BACKGROUND: Diabetic peripheral neuropathy (DPN) has been shown to be independently associated with cardiovascular events and mortality. This study aimed to evaluate changes in left ventricular (LV) microvascular perfusion and myocardial deformation in type 2 diabetes mellitus (T2DM) patients with and without DPN, as well as to investigate the association between myocardial perfusion and LV deformation. METHODS: Between October 2015 and July 2022, one hundred and twenty-three T2DM patients without DPN, fifty-four patients with DPN and sixty age­ and sex­matched controls who underwent cardiovascular magnetic resonance imaging were retrospectively analyzed. LV myocardial perfusion parameters at rest, including upslope, time to maximum signal intensity (TTM), max signal intensity (max SI), and myocardial strains, including global radial, circumferential and longitudinal strain (GRS, GCS and GLS, respectively), were calculated and compared among the groups with One­way analysis of variance. Univariable and multivariable linear regression analyses were performed to explore the independent factors influencing LV myocardial perfusion indices and LV strains in diabetes. RESULTS: The LV GLS, upslope and max SI were significantly deteriorated from controls, through patients without DPN, to patients with DPN (all P < 0.001). Compared with controls, TTM was increased and LV GRS and GCS were decreased in both patient groups (all P < 0.05). Multivariable regression analyses considering covariates showed that DPN was independently associated with reduced upslope, max SI and LV GLS (ß = - 0.360, - 2.503 and 1.113, p = 0.021, 0.031 and 0.010, respectively). When the perfusion indices upslope and max SI were included in the multivariable analysis for LV deformation, DPN and upslope (ß = 1.057 and - 0.870, p = 0.020 and 0.018, respectively) were significantly associated with LV GLS. CONCLUSION: In patients with T2DM, there was more severe LV microvascular and myocardial dysfunction in patients with complicated DPN, and deteriorated subclinical LV systolic dysfunction was associated with impaired myocardial circulation.

Left atrioventricular interaction and impaired left atrial phasic function in type 2 diabetes mellitus patients with or without anemia: a cardiac magnetic resonance study.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) and anemia are related to some cardiovascular diseases and can predict poor outcomes. Both of them can damage the heart in their own ways, but their combined effects have not been well explored. This study aimed to explore the combined effects of T2DM and anemia and the interaction between left atrial (LA) and left ventricular (LV) function by cardiac magnetic resonance (CMR). MATERIALS AND METHODS: A total of 177 T2DM patients without anemia, 68 T2DM patients with anemia and 73 sex-matched controls were retrospectively enrolled in this study from June 2015 to September 2022. Their LA phasic function and LV function parameters were compared to explore the combined effects of T2DM and anemia and the interaction between LA and LV function. Univariate and multivariate linear regression were done to explore the independent factors influencing LA phasic function and LV function. RESULTS: Compared with controls and T2DM patients without anemia, T2DM patients with anemia were older and had higher heart rate, higher creatinine, lower estimated glomerular filtration rate (eGFR) and lower hemoglobin (Hb) (all p < 0.05). LV global longitudinal peak strain (GLPS) significantly declined from T2DM patients with anemia to T2DM patients without anemia to controls (p < 0.001). LA volumetric function and strain were significantly impaired in T2DM patients with anemia compared with the other groups (all p < 0.05). In addition to age, eGFR, Hb and HbA1c, the LV GLPS was independently associated with all LA phasic strains (LA reservoir strain, ß =0.465; LA conduit strain, ß = 0.450; LA pump strain, ß = 0.360, all p < 0.05). LA global conduit strain, total LA ejection fraction (LAEF) and active LAEF were independently associated with LV GLPS and LVEF. CONCLUSION: Both LA and LV function were severely impaired in T2DM patients with anemia, and T2DM and anemia were independently associated with LA phasic function. Deleterious interaction between LA function and LV function would happen in T2DM patients with or without anemia. Timely and effective monitoring and management of both LA and LV function will benefit T2DM patients.

Cinnamon oil solid self-microemulsion mediates chronic mild stress-induced depression in mice by modulating monoamine neurotransmitters, corticosterone, inflammation cytokines, and intestinal flora.

Cinnamon oil (CO) is a classic Chinese medicine with excellent soothing effects on exhaustion, weakness and depression. Cinnamaldehyde is the main active ingredient of cinnamic oil. Although CO have antidepression-like effects, limited information is available. Furthermore, the disadvantages of CO, such as low oral availability and difficult portability, limit its development. In this study, a Cinnamon Oil Solid Self-Microemulsifying Drug Delivery System (CO-S-SME) was designed, prepared. In addition, we explored the effects and mechanisms of CO-S-SME on chronic unpredictable mild stress (CUMS)-induced depression-like behavior, monoamine neurotransmitters, inflammatory factors, intestinal flora in mice. Mice were subjected CUMS to establish the depression model. The antidepressant effect of CO-S-SME was evaluated by behavioral tests. In addition, the expression levels of neurotransmitters, corticosterone (CORT) and inflammatory factors in CUMS mice were analyzed by enzyme-linked immunosorbent assay. In addition, we explored the effects of CO-S-SME on the diversity and richness of intestinal flora of mice in each group. Behavioral tests showed that CO-S-SME could effectively improve depression-like behaviors in CUMS mice. Specifically, CO-S-SME treatment effectively increased neurotransmitter levels and reduced the expressions of corticosterone and inflammatory factors in CUMS mice. CO-S-SME also changed the intestinal flora composition, decreased the ratio of Firmicutes to Bacteroidetes, reduced relative abundances of Lactobacillus, modulated Alpha diversity and beta diversity. These results suggest that CO-S-SME an act as a good antidepressant, exhibiting effects via monoamine neurotransmitters, CORT, inflammation cytokines, and intestinal flora.

Myocardial Perfusion Imaging by Cardiovascular Magnetic Resonance: Research Progress and Current Implementation.

Cardiovascular diseases pose a significant health and economic burden worldwide, with coronary artery disease still recognized as a major problem. It is closely associated with hypertension, diabetes, obesity, smoking, lack of exercise, poor diet, and excessive alcohol consumption, which may lead to macro- and microvascular abnormalities in the heart. Coronary artery stenosis reduces the local supply of oxygen and nutrients to the myocardium and results in reduced levels of myocardial perfusion, which can lead to more severe conditions and irreversible damage to myocardial tissues. Therefore, accurate evaluation of myocardial perfusion abnormalities in patients with these risk factors is critical. As technology advances, magnetic resonance myocardial perfusion imaging has become more accurate at evaluating the myocardial microcirculation and has shown a powerful ability to detect myocardial ischemia. The purpose of this review is to summarize the principle, research progress of acquisition and analysis, and clinical implementation of cardiovascular magnetic resonance (CMR) myocardial perfusion imaging.

Sex-related Differences in Left Ventricular Deformation in Patients With Hypertensive Heart Failure With Reduced Ejection Fraction: Assessment by Cardiac Magnetic Resonance Tissue Tracking.

We aimed to investigate sex-related differences in left ventricular (LV) deformation in heart failure with reduced ejection fraction (HFrEF) patients with comorbid hypertension (HTN) by cardiac MRI. A total of 281 patients with HFrEF who underwent cardiac MRI were enrolled in this study. Sex-related differences in LV structure, function and strains derived from cardiac cine MRI in the context of HTN were measured and compared. The clinical variables associated with LV strains in HFrEF patients with comorbid HTN and determinants of impaired LV strains were investigated for both sexes. The prevalence of HTN did not differ between the sexes (P > 0.05). Despite having a similar LVEF, hypertensive men displayed decreased LV deformation in all 3 directions compared with hypertensive women (all P < 0.05). Male sex and its interaction with HTN were associated with higher LV mass index, reduced LV GCPS and GLPS compared with hypertensive women (all P < 0.05). Male sex was associated with LV deformation impairment in hypertensive HFrEF patients (all P < 0.05). After adjustment for covariates in HFrEF patients, HTN was found to be an independent determinant of impaired LV GCPS [ß = 0.17; P = 0.022] and GLPS [ß = 0.25; P < 0.001]) in men but not in women (all P > 0.05). Sex had a modifying effect on LV deformation in hypertensive HFrEF patients, with greater adverse effects on LV strains in men than in women. Sex-tailored treatment approaches may be considered in the future for HFrEF patients with comorbid HTN.

Prognostic Value of Left Atrial Reservoir Strain in Left Ventricular Myocardial Noncompaction: A 3.0 T Cardiac Magnetic Resonance Feature Tracking Study.

BACKGROUND: The relationship of left atrial (LA) strain to high-risk heart failure (HF) events in patients with left ventricular myocardial noncompaction (LVNC) remains to be thoroughly investigated. PURPOSE: To evaluate the LA performance in patients with LVNC, and to investigate the prognostic value of LA phasic strain on high-risk HF events, and its influencing factors. STUDY TYPE: Retrospective. POPULATION: A total of 95 LVNC patients (74 with LA enlargement [LAE] and 21 without LAE) and 50 healthy controls. FIELD STRENGTH/SEQUENCE: A 3.0 T, balanced steady-state free-precession cine imaging. ASSESSMENT: LA longitudinal strains were measured by cardiac MRI feature tracking technique. LA volume index (LAVI) and LA ejection fraction (LAEF) were calculated. Their intraobserver and interobserver reproducibility were evaluated. The primary outcome was high-risk HF events, a composite of first HF hospitalization, hospitalization for worsening HF and death from HF. STATISTICAL TESTS: Student's t/Mann-Whitney U, one-way analysis of variance/Kruskal-Wallis, Chi-squared, receiver operating characteristic, Kaplan-Meier, log-rank, Cox regression, Pearson and Spearman correlation and linear regression analyses were performed. The significance threshold was set at P < 0 .05. RESULTS: LAEF and LA longitudinal strains decreased in LVNC patients irrespective of the presence of LAE. During a median follow-up of 32.17 months, high-risk HF occurred in 13 (13.68%) patients. Patients with increased LAVI, decreased LAEF and decreased LA longitudinal strain had significantly higher risks of high-risk HF events. In patients with LVNC, LA reservoir strain (εs) was independently associated with high-risk HF (hazard ratio = 23.208 [95% CI: 2.993-179.967]). LV global longitudinal strain (LV GLS) (ß = -1.783 [95% CI: -2.493 to -1.073]) was significantly and independently associated with εs. Intraobserver and interobserver reproducibility was excellent for LAVI, LAEF, and LA strain. CONCLUSION: In patients with LVNC, εs was an independent predictor for high-risk HF events. LV GLS was an independent determinant of εs in LVNC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 4.

The Impact of Hypertension on Left Ventricular Function and Remodeling in Non-Ischemic Dilated Cardiomyopathy Patients: A 3.0 T MRI Study.

BACKGROUND: Hypertension (HTN) is highly prevalent in non-ischemic dilated cardiomyopathy (NIDCM) patients, but little is known about its impact on left ventricular (LV) function and remodeling. PURPOSE: To evaluate the effect of hypertension on LV function and remodeling in NIDCM patients. STUDY TYPE: Retrospective. POPULATION: Two-hundred and twelve NIDCM (HTN-) patients, 91 NIDCM (HTN+) patients, and 74 normal controls. FIELD STRENGTH/SEQUENCE: 3.0 T/bSSFP and phase-sensitive inversion recovery sequence. ASSESSMENT: The LV geometry, myocardial strain, remodeling index (calculated as LVM/LVEDV), and LGE were measured and compared between groups. Determinants of LV strain and remodeling in NIDCM were investigated. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, one-way analysis of variance, Kruskal-Wallis test, univariable and multivariable linear regression. A P value <0.05 was considered statistically significant. RESULTS: Compared with normal controls, NIDCM patients had significantly higher LVEDV and significantly impaired LV strains, including LV global peak strain (PS) and peak systolic and diastolic strain rates in the radial, circumferential, and longitudinal directions. The NIDCM (HTN+) group had significantly decreased LV global longitudinal PS and peak diastolic strain rate (PDSR), and significantly increased LV mass index and remodeling index compared to the NIDCM (HTN-) group, despite there being no significant difference in ejection fraction (P = 0.241). The prevalence of LV LGE was significantly higher in the NIDCM (HTN+) group than in the NIDCM (HTN-) group. In multivariable regression models adjusted for potential confounders, hypertension was independently associated with LV global longitudinal PS and PDSR. Male sex, resting heart rate, and log(NT-proBNP) level were independent determinants of LV strains. Moreover, male sex, systolic and diastolic blood pressure, and presence of LGE were independent determinants of LV remodeling index. DATA CONCLUSION: These findings suggest that coexistence of hypertension may further exacerbate the reduction in LV global strain and the aggravation of LV remodeling in NIDCM patients. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Hepatic ARID3A facilitates liver cancer malignancy by cooperating with CEP131 to regulate an embryonic stem cell-like gene signature.

Liver cancer stemness refers to the stem cell-like phenotype of hepatocarcinoma cells and is closely related to a high degree of tumour malignancy. Here, we identified AT-rich interacting domain 3A (ARID3A) as one of the most upregulated stemness-related transcription factors in liver cancer by an in vitro functional screen. ARID3A can promote liver cancer cell viability and metastasis both in vitro and in vivo. Mechanistically, ARID3A interacts with CEP131 and transcriptionally activates KDM3A by co-occupying its promoter element, further upregulating the expression of downstream embryonic stem (ES) signature genes via demethylation of H3K9me2. ARID3A and CEP131 promote an ES cell gene signature through activation of KDM3A and contribute to the poor prognosis of liver cancer patients. Collectively, these results provide evidence highlighting a transcription-dependent mechanism of ARID3A in stemness regulation in liver cancer. The ARID3A/CEP131-KDM3A regulatory circuit could serve as a prognostic indicator and potential therapeutic target for liver cancer.

Atrioventricular coupling and left atrial abnormality in type 2 diabetes mellitus with functional mitral regurgitation patients verified by cardiac magnetic resonance imaging.

BACKGROUND: Functional mitral regurgitation (FMR) in type 2 diabetes mellitus (T2DM) patients induced by left ventricular (LV) enlargement and mitral valve abnormality may aggravated the impairment in left atrial (LA) compliance. Thus, this study aimed to depict how FMR and LV dysfunction affect LA compliance in T2DM patients with FMR. MATERIALS AND METHODS: A total of 148 patients with T2DM and 49 age- and sex-matched normal controls underwent cardiac magnetic resonance examination. LA longitudinal strain and LA and LV functional indices were compared among controls and different T2DM patients. The multivariate analysis was used to identify the independent indicators of LA longitudinal strain. RESULTS: T2DM Patients without FMR had a lower total LA empty fraction (LAEF) compared with the controls (all P < 0.05). T2DM patients with mild and moderate FMR showed increased LA volume (LAV) and LV volume while decreased LAEF, LA strain, and LV ejection fraction (P < 0.05). T2DM patients with severe FMR showed markedly increased LAV and LV volume while decreased LAEF, LA strain, and LVEF (P < 0.05). In T2DM patients with FMR, reservoir strain (εs) was independently correlated with LV end-diastolic volume (LVEDV) (ß = - 0.334) and regurgitation degree (ß = - 0.256). The passive strain (εe) was independently correlated with regurgitation degree (ß = - 0.297), whereas the active strain (εa) was independently correlated with LVESV (ß = - 0.352) and glycated haemoglobin (ß = - 0.279). CONCLUSION: FMR may aggravate LA and LV dysfunction in T2DM patients. Regurgitation degree was an independent determinant of the εs and the εe, LVEDV was an independent determinant of the εs, and LVESV was an independent determinant of the εa in T2DM patients with FMR.

Impact of type 2 diabetes mellitus on left ventricular deformation in non-ischemic dilated cardiomyopathy patients assessed by cardiac magnetic resonance imaging.

BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of worse long-term outcomes in patients with non-ischemic dilated cardiomyopathy (NIDCM). However, the additive effects of T2DM on left ventricular (LV) function in NIDCM remain unclear. Accordingly, we aimed to investigate the impact of comorbid T2DM on LV deformation in NIDCM individuals. MATERIALS AND METHODS: Three hundred forty-two NIDCM patients without T2DM [NIDCM (T2DM-)], 93 with T2DM [NIDCM (T2DM+)] and 80 age- and sex-matched normal controls who underwent cardiac magnetic resonance scanning were included. LV geometry, function, and LV global strains, including peak strain (PS), peak systolic strain rate (PSSR) and peak diastolic strain rate (PDSR) in the radial, circumferential and longitudinal directions, were measured. NIDCM (T2DM+) patients were divided into two subgroups based on the HbA1c level (< 7.0% and ≥ 7.0%). The determinants of reduced LV myocardial strain for all NIDCM individuals and NIDCM (T2DM+) patients were assessed using multivariable linear regression analyses. RESULTS: Compared with normal controls, both NIDCM (T2DM -) and NIDCM (T2DM+) patients exhibited increased LV end-diastolic and end-systolic volume index and decreased LV ejection fraction. LV global strains progressively declined from the normal controls to the NIDCM (T2DM-) group to the NIDCM (T2DM+) group (all p < 0.017), except for radial PDSR and PSSR. Subgroup analysis showed that LV global radial PS and longitudinal PS, PSSR-L and PDSR-L were worse in NIDCM patients with poor glycemic control than in those with good glycemic control (p < 0.017). T2DM was an independent determinant of reduced LV global circumferential PS and longitudinal PS in patients with NIDCM (both p < 0.05). An increased HbA1c level was independently associated with a decreased global radial PS (ß = - 0.285, p < 0.01) and longitudinal PS (ß = 0.320, p < 0.01) in NIDCM (T2DM+) patients. CONCLUSIONS: T2DM has an additive deleterious effect on LV systolic and diastolic function in NIDCM patients. Among NIDCM patients with T2DM, HbA1c was found to be associated with reduced LV myocardial strain.

RNA binding protein RALY activates the cholesterol synthesis pathway through an MTA1 splicing switch in hepatocellular carcinoma.

Alternative splicing is an important RNA processing event that contributes to RNA complexity and protein diversity in cancer. Accumulating evidence demonstrates the essential roles of some alternatively spliced genes in carcinogenesis. However, the potential roles of alternatively spliced genes in hepatocellular carcinoma (HCC) are still largely unknown. Here we showed that the HnRNP Associated with Lethal Yellow Protein Homolog (RALY) gene is upregulated and associated with poor outcomes in HCC patients. RALY acts as a tumor-promoting factor by cooperating with splicing factor 3b subunit 3 (SF3B3) and modulating the splicing switch of Metastasis Associated 1 (MTA1) from MTA-S to MTA1-L. Normally, MTA1-S inhibits cell proliferation by reducing the transcription of cholesterol synthesis genes. In HCC, RALY and SF3B3 cooperate to regulate the MTA1 splicing switch, leading to a reduction in the MTA1-S level, and alleviating the inhibitory effect of MTA1-S on cholesterol synthesis genes, thus promoting HCC cell proliferation. In conclusion, our results revealed that the RALY-SF3B3/MTA1/cholesterol synthesis pathway contributes essentially to hepatic carcinogenesis and could serve as a promising therapeutic target for HCC.

Cardiac magnetic resonance T1 mapping for evaluating myocardial fibrosis in patients with type 2 diabetes mellitus: correlation with left ventricular longitudinal diastolic dysfunction.

OBJECTIVES: We aimed to evaluate myocardial fibrosis using cardiac magnetic resonance (CMR) T1 mapping in type 2 diabetes mellitus (T2DM) patients and investigate the association between left ventricular (LV) subclinical myocardial dysfunction and myocardial fibrosis. METHODS: The study included 37 short-term (≤ 5 years) and 44 longer-term (> 5 years) T2DM patients and 41 healthy controls. The LV global strain parameters and T1 mapping parameters were compared between the abovementioned three groups. The association of T1 mapping parameters with diabetes duration, in addition to other risk factors, was determined using multivariate linear regression analysis. The correlation between LV strain parameters and T1 mapping parameters was evaluated using Pearson's correlation. RESULTS: The peak diastolic strain rates (PDSRs) were significantly lower in longer-term T2DM patients compared to those in healthy subjects and short-term T2DM patients (p < 0.05). The longitudinal peak systolic strain rate and peak strain were significantly lower in the longer-term T2DM compared with the short-term T2DM group (p < 0.05). The extracellular volumes (ECVs) were higher in both subgroups of T2DM patients compared with control subjects (all p < 0.05). Multivariate linear regression analysis showed that diabetes duration was independently associated with ECV (ß = 0.413, p < 0.001) by taking covariates into account. Pearson's analysis showed that ECV was associated with longitudinal PDSR (r = - 0.441, p < 0.001). CONCLUSION: T1 mapping could detect abnormal myocardial fibrosis early in patients with T2DM, which can cause a decline in the LV diastolic function. KEY POINTS: • CMR T1 mapping could detect abnormal myocardial fibrosis early in patients with T2DM. • The diabetes duration was independently associated with ECV. • Myocardial fibrosis can cause a decline in the LV diastolic function in T2DM patients.