Sex differences in clinical profile, left ventricular remodeling and cardiovascular outcomes among diabetic patients with heart failure and reduced ejection fraction: a cardiac-MRI-based study.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is associated with a high rate of mortality and morbidity. Evidence has shown that sex differences may be an important contributor to phenotypic heterogeneity in patients with HFrEF. Although diabetes mellitus (DM) frequently coexists with HFrEF and results in a worse prognosis, there remains a need to identify sex-related differences in the characteristics and outcomes of this population. In this study, we aimed to investigate the between-sex differences in clinical profile, left ventricular (LV) remodeling, and cardiovascular risk factors and outcomes in patients with HFrEF concomitant with DM. METHODS: A total of 273 patients with HFrEF concomitant with DM who underwent cardiac MRI were included in this study. Clinical characteristics, LV remodeling as assessed by cardiac MRI, and cardiovascular risk factors and outcomes were compared between sexes. RESULTS: Women were older, leaner and prone to have anemia and hypoproteinemia but less likely to have ischemic etiology. Cardiac MRI revealed that despite similar LVEFs between the sexes, there was more LV concentric remodeling, less impaired global systolic peak strain in longitudinal and circumferential components and a decreased likelihood of late gadolinium enhancement presence in women than in men. During a median follow-up time of 34.6 months, women exhibited better overall survival than men did (log-rank P = 0.042). Multivariable Cox proportional hazards analysis indicated different risk factors for predicting outcomes between sexes, with hypertension [hazard ratio (HR) = 2.05, 95% confidence interval (CI) 1.05 to 4.85, P = 0.041] and hypoproteinemia (HR = 2.27, 95% CI 1.06 to 4.37, P = 0.039) serving as independent determinants of outcomes in women, whereas ischemic etiology (HR = 1.96, 95% CI 1.11 to 3.48, P = 0.021) and atrial fibrillation (HR = 1.86, 95% CI 1.02 to 3.41, P = 0.044) served as independent determinants of outcomes in men. CONCLUSIONS: Among patients with HFrEF concomitant with DM, women displayed different LV remodeling and risk factors and had better survival than men did. Sex-based phenotypic heterogeneity in patients with HFrEF in the context of DM should be addressed in clinical practice.

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.

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.

Effect of Metabolic Syndrome on Left Atrial and Left Ventricular Deformation and Atrioventricular Interactions in Patients With Myocardial Infarction.

BACKGROUND: Metabolic syndrome (MetS) is associated with worse prognosis in patients with myocardial infarction (MI). However, it is unclear how MetS in MI patients is associated with left atrial (LA) and left ventricular (LV) deformation. PURPOSE: To determine the effect of MetS on LA and LV deformation and atrioventricular interactions in MI patients. STUDY TYPE: Retrospective. POPULATION: One hundred eighty-one MI patients (73 MetS+ and 108 MetS-), 107 age- and sex-matched controls (49 MetS+ and 58 MetS-). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession (SSFP)/segmented phase-sensitive inversion recovery SSFP sequence. ASSESSMENT: LA strain and strain rates (reservoir, conduit, and active), left atrioventricular coupling index (LACI), and LV geometry and radial, circumferential and longitudinal global peak strains (PS) were compared among groups. STATISTICAL TESTS: Two-way analysis of variance, Spearman and Pearson's correlation coefficients, and multivariable linear regression analysis. P value <0.05 indicated statistical significance. RESULTS: Compared with controls, the MI patients with or without MetS showed impaired LA function (reservoir, conduit, and active) and LV deformation (radial, circumferential, and longitudinal PS) and higher LACI. The MetS+ group had lower LA reservoir and conduit function and LV deformation than MetS- group. The MetS-MI interaction was not statistically significant. Furthermore, multivariable linear regression showed that MetS was independently associated with LA and LV deformation (ß = -0.181 to -0.209) in MI patients; LA function was independently associated with LV circumferential PS (ß = 0.230 to 0.394) and longitudinal PS (ß = 0.189 to 0.420), and LA passive strain and strain rate were negatively associated with LV mass (ß = -0.178 and -0.298). DATA CONCLUSION: MetS may be associated with the LA and LV dysfunction in MI patients. Impaired LV deformation and LV hypertrophy are independently associated with LA dysfunction in MI patients, and the MI patients have higher LACI than controls, suggesting atrioventricular interaction alterations. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 3.

Reduced thoracic skeletal muscle size is associated with adverse outcomes in diabetes patients with heart failure and reduced ejection fraction: quantitative analysis of sarcopenia by using cardiac MRI.

BACKGROUND: Sarcopenia is frequently found in patients with heart failure with reduced ejection fraction (HFrEF) and is associated with reduced exercise capacity, poor quality of life and adverse outcomes. Recent evidence suggests that axial thoracic skeletal muscle size could be used as a surrogate to assess sarcopenia in HFrEF. Since diabetes mellitus (DM) is one of the most common comorbidities with HFrEF, we aimed to explore the potential association of axial thoracic skeletal muscle size with left ventricular (LV) remodeling and determine its prognostic significance in this condition. METHODS: A total of 243 diabetes patients with HFrEF were included in this study. Bilateral axial thoracic skeletal muscle size was obtained using cardiac MRI. Patients were stratified by the tertiles of axial thoracic skeletal muscle index (SMI). LV structural and functional indices, as well as amino-terminal pro-B-type natriuretic peptide (NT-proBNP), were measured. The determinants of elevated NT-proBNP were assessed using linear regression analysis. The associations between thoracic SMI and clinical outcomes were assessed using a multivariable Cox proportional hazards model. RESULTS: Patients in the lowest tertile of thoracic SMI displayed a deterioration in LV systolic strain in three components, together with an increase in LV mass and a heavier burden of myocardial fibrosis (all P < 0.05). Moreover, thoracic SMI (ß = -0.25; P < 0.001), rather than body mass index (ß = -0.04; P = 0.55), was independently associated with the level of NT-proBNP. The median follow-up duration was 33.6 months (IQR, 20.4-52.8 months). Patients with adverse outcomes showed a lower thoracic SMI (40.1 [34.3, 47.9] cm2/m2 vs. 45.3 [37.3, 55.0] cm2/m2; P < 0.05) but a similar BMI (P = 0.76) compared with those without adverse outcomes. A higher thoracic SMI indicated a lower risk of adverse outcomes (hazard ratio: 0.96; 95% confidence interval: 0.92-0.99; P = 0.01). CONCLUSIONS: With respect to diabetes patients with HFrEF, thoracic SMI is a novel alternative for evaluating muscle wasting in sarcopenia that can be obtained by a readily available routine cardiac MRI protocol. A reduction in thoracic skeletal muscle size predicts poor outcomes in the context of DM with HFrEF.

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.

Assessment of left atrioventricular coupling and left atrial function impairment in diabetes with and without hypertension using CMR feature tracking.

PURPOSE: The study was designed to assess the effect of co-occurrence of diabetes mellitus (DM) and hypertension on the deterioration of left atrioventricular coupling index (LACI) and left atrial (LA) function in comparison to individuals suffering from DM only. METHODS: From December 2015 to June 2022, we consecutively recruited patients with clinically diagnosed DM who underwent cardiac magnetic resonance (CMR) at our hospital. The study comprised a total of 176 patients with DM, who were divided into two groups based on their blood pressure status: 103 with hypertension (DM + HP) and 73 without hypertension (DM-HP). LA reservoir function (reservoir strain (εs), total LA ejection fraction (LAEF)), conduit function (conduit strain (εe), passive LAEF), booster-pump function (booster strain (εa) and active LAEF), LA volume index (LAVI), LV global longitudinal strain (LVGLS), and LACI were evaluated and compared between the two groups. RESULTS: After adjusting for age, sex, body surface area (BSA), and history of current smoking, total LAEF (61.16 ± 14.04 vs. 56.05 ± 12.72, p = 0.013) and active LAEF (43.98 ± 14.33 vs. 38.72 ± 13.51, p = 0.017) were lower, while passive LAEF (33.22 ± 14.11 vs. 31.28 ± 15.01, p = 0.807) remained unchanged in the DM + HP group compared to the DM-HP group. The DM + HP group had decreased εs (41.27 ± 18.89 vs. 33.41 ± 13.94, p = 0.006), εe (23.69 ± 12.96 vs. 18.90 ± 9.90, p = 0.037), εa (17.83 ± 8.09 vs. 14.93 ± 6.63, p = 0.019), and increased LACI (17.40±10.28 vs. 22.72±15.01, p = 0.049) when compared to the DM-HP group. In patients with DM, multivariate analysis revealed significant independent associations between LV GLS and εs (ß=-1.286, p < 0.001), εe (ß=-0.919, p < 0.001), and εa (ß=-0.324, p = 0.036). However, there was no significant association observed between LV GLS and LACI (ß=-0.003, p = 0.075). Additionally, hypertension was found to independently contribute to decreased εa (ß=-2.508, p = 0.027) and increased LACI in individuals with DM (ß = 0.05, p = 0.011). CONCLUSIONS: In DM patients, LV GLS showed a significant association with LA phasic strain. Hypertension was found to exacerbate the decline in LA booster strain and increase LACI in DM patients, indicating potential atrioventricular coupling index alterations.

Biventricular Dysfunction and Ventricular Interdependence in Patients With Pulmonary Hypertension: A 3.0-T Cardiac MRI Feature Tracking Study.

BACKGROUND: Pulmonary hypertension (PH) results in right ventricular (RV) dysfunction, subsequently leading to left ventricular (LV) impairment. The mechanism underlying ventricular interdependence is largely uninvestigated. PURPOSE: To explore the biventricular dysfunction and the ventricular interdependence in PH patients. STUDY TYPE: Retrospective. POPULATION: One hundred and seven PH patients (mean pulmonary artery pressure >20 mmHg) and 72 age- and sex-matched controls with cardiac magnetic resonance imaging (MRI) studies. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence. ASSESSMENT: LV and RV ejection fractions (EF) and RV and LV radial, circumferential, and longitudinal strains were assessed using commercial software. Strains were compared between controls, PH patients with preserved RVEF (RVEF ≥40%, N = 48), and PH patients with reduced RVEF (RVEF <40%, N = 59). STATISTICAL TESTS: Chi-squared tests or Fisher's exact test, t tests or Mann-Whitney U test, one-way ANOVA with Bonferroni's post hoc correction or Kruskal-Wallis test, Pearson or Spearman correlation, and multivariable linear regression analysis. A two-tailed P < 0.05 was deemed statistically significant. RESULTS: RV strain decreased sequentially from controls, through PH with preserved RVEF, to PH with reduced RVEF. PH patients with reduced RVEF had significantly lower LV strain, especially septal strain, and LV peak diastolic strain rate compared with both controls and PH patients with preserved RVEF. Multivariable analyses showed that RVEF was independently correlated with LV strain; furthermore, independent of RVEF, RV strain was significantly correlated with LV strain (LVGRS: ß = 0.416; LVGCS: ß = -0.371; LVGLS: ß = 0.283). DATA CONCLUSION: Subclinical impairment of RV function was found in PH with preserved RVEF. LV strain was impaired when RV was dysfunctional, which was associated with worsening RV strain. Therefore, while focusing on improving RV function, LV dysfunction in PH patients should also be monitored and treated early in order to slow the progression of the disease. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Association of insulin use with LV remodeling and clinical outcomes in diabetic patients with heart failure and reduced ejection fraction: assessed by cardiac MRI.

BACKGROUND: Insulin is commonly used in type 2 diabetes mellitus (T2DM) to achieve glycemic control. However, recent evidence showed that insulin use is associated with poor outcomes in the context of heart failure (HF). Since heart failure with reduced ejection fraction (HFrEF) accounts for approximately 50% of cases in the general HF population, we aimed to evaluate the effect of insulin treatment on left ventricular (LV) remodeling and contractility abnormalities in a HFrEF cohort and assess whether insulin was a predictor of adverse outcomes in this entity. METHODS: A total of 377 HFrEF patients who underwent cardiac MRI were included and divided according to diabetes status and the need for insulin treatment. LV structural and functional indices, as well as systolic strains, were measured. The determinants of impaired myocardial strains were assessed using linear regression analysis. The associated endpoints were determined using a multivariable Cox proportional hazards model. RESULTS: T2DM patients on insulin displayed a higher indexed LV end-diastolic volume and LV mass than those with T2DM not on insulin or those without T2DM, despite similar LV ejection fractions, accompanied by a higher three-dimensional spherical index (P < 0.01). Worse longitudinal and circumferential peak systolic strain was shown to occur in T2DM patients on insulin (P < 0.01). Insulin treatment was independently associated with impaired magnitudes of systolic strain. The median follow-up duration was 32.4 months (IQR, 15.6-43.2 months). Insulin treatment remained consistently associated with poor outcomes after adjustment for established confounders, with an adjusted hazard ratio of 3.11; (95% CI, 1.45-6.87; P = 0.009) in the overall cohort and 2.16 (95% CI, 1.08-4.59; P = 0.030) in the diabetes cohort. CONCLUSIONS: Insulin may further lead to adverse LV remodeling and contractile dysfunction in the context of HFrEF with T2DM. Considerable care should be taken when treating HFrEF patients with insulin.

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.

Incremental effect of coronary obstruction on myocardial microvascular dysfunction in type 2 diabetes mellitus patients evaluated by first-pass perfusion CMR study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) frequently coexists with obstructive coronary artery disease (OCAD), which are at increased risk for cardiovascular morbidity and mortality. This study aimed to investigate the impact of coronary obstruction on myocardial microcirculation function in T2DM patients, and explore independent predictors of reduced coronary microvascular perfusion. METHODS: Cardiac magnetic resonance (CMR) scanning was performed on 297 T2DM patients {188 patients without OCAD [T2DM(OCAD -)] and 109 with [T2DM(OCAD +)]} and 89 control subjects. CMR-derived perfusion parameters, including upslope, max signal intensity (MaxSI), and time to maximum signal intensity (TTM) in global and segmental (basal, mid-ventricular, and apical slices) were measured and compared among observed groups. According to the median of Gensini score (64), T2DM(OCAD +) patients were subdivided into two groups. Univariable and multivariable linear regression analyses were performed to identify independent predictors of microcirculation dysfunction. RESULTS: T2DM(OCAD -) patients, when compared to control subjects, had reduced upslope and prolonged TTM in global and all of three slices (all P < 0.05). T2DM(OCAD +) patients showed a significantly more severe impairment of microvascular perfusion than T2DM(OCAD -) patients and control subjects with a more marked decline upslope and prolongation TTM in global and three slices (all P < 0.05). From control subjects, through T2DM(OCAD +) patients with Gensini score ≤ 64, to those patients with Gensini score > 64 group, the upslope declined and TTM prolonged progressively in global and mid-ventricular slice (all P < 0.05). The presence of OCAD was independently correlated with reduced global upslope (ß = - 0.104, P < 0.05) and global TTM (ß = 0.105, P < 0.05) in patients with T2DM. Among T2DM(OCAD +) patients, Gensini score was associated with prolonged global TTM (r = 0.34, P < 0.001). CONCLUSIONS: Coronary artery obstruction in the context of T2DM exacerbated myocardial microcirculation damage. The presence of OCAD and Gensini score were independent predictors of decreased microvascular function. TRIAL REGISTRATION: Retrospectively registered.

The right ventricular dysfunction and ventricular interdependence in patients with DM: assessment using cardiac MR feature tracking.

BACKGROUND: To investigate the difference of right ventricular (RV) structural and functional alteration in patients with diabetes mellitus (DM) with preserved left ventricular ejection fraction (LVEF), and the ventricular interdependence in these patients, using cardiac MR (CMR) feature tracking. METHODS: From December 2016 to February 2022, 148 clinically diagnosed patients with DM who underwent cardiac MR (CMR) in our hospital were consecutively recruited. Fifty-four healthy individuals were included as normal controls. Biventricular strains, including left/right ventricular global longitudinal strain (LV-/RVGLS), left/right ventricular global circumferential strain (LV-/RVGCS), left/right ventricular global radial strain (LV-/RVGRS) were evaluated, and compared between patients with DM and healthy controls. Multiple linear regression and mediation analyses were used to evaluate DM's direct and indirect effects on RV strains. RESULTS: No differences were found in age (56.98 ± 10.98 vs. 57.37 ± 8.41, p = 0.985), sex (53.4% vs. 48.1%, p = 0.715), and body surface area (BSA) (1.70 ± 0.21 vs. 1.69 ± 0.17, p = 0.472) between DM and normal controls. Patients with DM had decreased RVGLS (- 21.86 ± 4.14 vs. - 24.49 ± 4.47, p = 0.001), RVGCS (- 13.16 ± 3.86 vs. - 14.92 ± 3.08, p = 0.011), and no decrease was found in RVGRS (22.62 ± 8.11 vs. 23.15 ± 9.05, p = 0.743) in patients with DM compared with normal controls. The difference in RVGLS between normal controls and patients with DM was totally mediated by LVGLS (indirect effecting: 0.655, bootstrapped 95%CI 0.138-0.265). The difference in RVGCS between normal controls and DM was partly mediated by the LVGLS (indirect effecting: 0.336, bootstrapped 95%CI 0.002-0.820) and LVGCS (indirect effecting: 0.368, bootstrapped 95%CI 0.028-0.855). CONCLUSIONS: In the patients with DM and preserved LVEF, the difference in RVGLS between DM and normal controls was totally mediated by LVGLS. Although there were partly mediating effects of LVGLS and LVGCS, the decrease in RVGCS might be directly affected by the DM.

Early evaluation of severe immune checkpoint inhibitor-associated myocarditis: a real-world clinical practice.

PURPOSE: Immune checkpoint inhibitor (ICI)-associated myocarditis is a rare but severe complication for patients treated with immunotherapy. This study aims to explore the predictive significance of patients' clinical features and examination results for the severity of ICI-associated myocarditis. METHODS: Data from a real-world cohort of 81 cancer patients who developed ICI-associated myocarditis after immunotherapy were retrospectively analyzed. The development of myocarditis of Common Terminology Criteria for Adverse Events (CTCAE) grades 3-5 and/or the major adverse cardiovascular event (MACE) was set as endpoints. Logistic regression was used to evaluate the predictive value of each factor. RESULTS: CTCAE grades 3-5 and MACE developed in 43/81 (53.1%) and 28/81 (34.6%) cases, respectively. The likelihood of CTCAE grades 3-5 and MACE increased with the accumulation of organs affected by the ICI-associated adverse events and initial clinical symptoms. Concurrent systematic therapies during ICI treatment did not raise the risk of myocarditis severity, while prior chemotherapy did. Besides classical serum cardiac markers, a higher neutrophil ratio was also related to poorer cardiac outcomes, whereas higher lymphocyte and monocyte ratios were predictors of favorable cardiac outcomes. The CD4+ T cell ratio and CD4/CD8 ratio were negatively related to CTCAE grades 3-5. Several cardiovascular magnetic resonance parameters were associated with myocarditis severity, whereas the predictive value of echocardiography and electrocardiogram was weak. CONCLUSION: This study comprehensively evaluated the prognostic value of patients' clinical characteristics and examination results and identified several predictors of severe ICI-associated myocarditis, which will facilitate early detection of severe ICI-associated myocarditis in patients receiving immunotherapy.

CT Radiomics Predict EGFR-T790M Resistance Mutation in Advanced Non-Small Cell Lung Cancer Patients After Progression on First-line EGFR-TKI.

RATIONALE AND OBJECTIVES: We aim to explore the value of chest CT radiomics in predicting the epidermal growth factor receptor (EGFR)-T790M resistance mutation of advanced non-small cell lung cancer (NSCLC) patients after the failure of first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI). MATERIALS AND METHODS: A total of 211 and 135 advanced NSCLC patients with tumor tissue-based (Cohort-1) or circulating tumor DNA (ctDNA)-based (Cohort-2) EGFR-T790M testing were included, respectively. Cohort-1 was used for modeling and Cohort-2 was for models' validation. Radiomic features were extracted from tumor lesions on chest nonenhanced CT (NECT) and/or contrast-enhanced CT (CECT). We used eight feature selectors and eight classifier algorithms to establish radiomic models. Models were evaluated by area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: CT morphological manifestations of peripheral location and pleural indentation sign were associated with EGFR-T790M. For NECT, CECT, and NECT+CECT radiomic features, the feature selector and classifier algorithms of LASSO and Stepwise logistic regression, Boruta and SVM, and LASSO and SVM were chosen to develop the optimal model, respectively (AUC: 0.844, 0.811, and 0.897). All models performed well in calibration curves and DCA. Independent validation of models in Cohort-2 revealed that both NECT and CECT models individually had limited power for predicting EGFR-T790M mutation detected by ctDNA (AUC: 0.649, 0.675), while the NECT+CECT radiomic model had a satisfactory AUC (0.760). CONCLUSION: This study proved the feasibility of using CT radiomic features to predict the EGFR-T790M resistance mutation, which could be helpful in guiding personalized therapeutic strategies.

The worsening effect of anemia on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T CMR feature tracking study.

OBJECTIVE: To explore the additive effects of anemia on left ventricular (LV) global strains in patients with type 2 diabetes mellitus (T2DM) with or without anemia via cardiac magnetic resonance (CMR) feature tracking technology. MATERIALS AND METHODS: 236 T2DM patients with or without anemia and 67 controls who underwent CMR examination were retrospectively enrolled. LV function parameters, LV global radial peak strain (GRPS), longitudinal peak strain (GLPS), and circumferential peak strain (GCPS) were used to analyze the function and global strain of the heart. One-way analysis of variance and the chi-square test were used for intergroup analysis. Multivariable linear regression analysis was performed for the two T2DM groups to explore factors associated with LV global strains. RESULTS: The T2DM group with anemia was oldest and had a lowest hemoglobin (Hb) concentration, lowest estimated glomerular filtration rate, highest LV end-systolic volume index, highest end-diastolic volume index and highest LV mass index than the control group and T2DM without anemia group (all P ≤ 0.001). Besides, The LV global peak strains in all three directions worsened successively from the control group to the T2DM without anemia group to the T2DM with anemia group (all p < 0.001). Among all clinical indices, the decrease in Hb was independently associated with the worsening in GRPS (ß = 0.237, p = 0.001), GCPS (ß = 0.326, p < 0.001), and GLPS (ß = 0.265, p < 0.001). CONCLUSION: Anemia has additive deleterious effects on LV function and LV global strains in patients with T2DM. Regular detection and early intervention of anemia might be beneficial for T2DM patients.

Unsupervised machine learning based on clinical factors for the detection of coronary artery atherosclerosis in type 2 diabetes mellitus.

BACKGROUND: Coronary atherosclerosis can lead to serious cardiovascular events. In type 2 diabetes (T2DM) patients, the effects of clinical factors on coronary atherosclerosis have not been fully elucidated. We used a clustering method to distinguish the population heterogeneity of T2DM and the differences in coronary atherosclerosis evaluated on coronary computed tomography angiography (CCTA) among groups and to facilitate clinical management. METHODS: Clinical data from 1157 T2DM patients with coronary atherosclerosis who underwent CCTA in our hospital from January 2018 to September 2021 were retrospectively collected. The coronary artery segment plaque type and stenosis, the number of involved vessels, the segment involvement score (SIS) and the segment stenosis score (SSS) were evaluated and calculated. Unsupervised clustering analysis based on clinical information was used (cluster 1: n = 463; cluster 2: n = 341; cluster 3: n = 353). The association of coronary plaque characteristics with cluster groups was evaluated. RESULTS: The clinical data among the three groups were different in several aspects: (1) Cluster 1 had the least male patients (41.7%), the lowest proportion of patients with smoking (0%) or alcohol history (0.9%), and the lowest level of serum creatinine (74.46 ± 22.18 µmol/L); (2) Cluster 2 had the shortest duration of diabetes (7.90 ± 8.20 years) and was less likely to be treated with diabetes (42.2%) or statins (17.6%) and (3) Cluster 3 was the youngest (65.89 ± 10.15 years old) and had the highest proportion of male patients (96.6%), the highest proportion of patients with smoking (91.2%) and alcohol (59.8%) history, the highest level of eGFR (83.81 ± 19.06 ml/min/1.73m2), and the lowest level of HDL-C (1.07 ± 0.28 mmol/L). The CCTA characteristics varied with different clusters: (1) Cluster 1 had the largest number of segments with calcified plaques (2.43 ± 2.46) and the least number of segments with mixed plaques (2.24 ± 2.59) and obstructive stenosis (0.98 ± 2.00); (2) Cluster 1 had the lowest proportion of patients with mixed plaques (68%) and obstructive stenosis (32.2%); (3) Cluster 3 had more segments with noncalcified plaques than cluster 1 (0.63 ± 1.02 vs 0.40 ± 0.78, P < 0.05) and the highest proportion of patients with noncalcified plaques (39.9%) and (4) There was no significant difference in the extent of coronary plaques among the three clusters. CONCLUSIONS: The unsupervised clustering method could address T2DM patients with heterogeneous clinical indicators and identify groups with different types of coronary plaque and degrees of coronary stenosis. This method has the potential for patient stratification, which is essential for the clinical management of T2DM patients with coronary atherosclerosis.

Adverse association of epicardial adipose tissue accumulation with cardiac function and atrioventricular coupling in postmenopausal women assessed by cardiac magnetic resonance imaging.

Background: This study aims to investigate the association of epicardial adipose tissue (EAT) accumulation with cardiac function and atrioventricular coupling in a cohort of postmenopausal women assessed by cardiac magnetic resonance imaging (CMR). Materials and methods: Overall, 283 postmenopausal women (mean age 61.5 ± 9.1 years) who underwent CMR examination were enrolled. Participants were classified into four groups by the quartile of EAT volume. EAT volume was quantified on short-axis cine stacks covering the entire epicardium. CMR-derived cardiac structure and function, including left atrial (LA)- volume, emptying fraction, deformation, and left ventricular (LV)- mass, volume, ejection fraction, and deformation, were compared among the four groups of graded EAT volume. Results: Left ventricular mass (LVM) and LV remodeling index were both increased in the group with the highest EAT volume, compared to those in the lowest quartile (p = 0.016 and p = 0.003). The LV global longitudinal strain (LV-GLS), circumferential strain (LV-GCS), and LA- reservoir strain (LA-RS), conduit strain (LA-CS), and booster strain (LA-BS), were all progressively decreased from the lowest quartile of EAT volume to the highest (all p < 0.05). Multivariable linear regression analyses showed that EAT was independently associated with LV-GLS, LA-RS, LA-CS, and LA-BS after adjusting for body mass index and other clinical factors. Conclusion: Epicardial adipose tissue accumulation is independently associated with subclinical LV and LA function in postmenopausal women. These associations support the role of EAT in mediating deleterious effects on cardiac structure and function.

Association of magnitude of weight loss and weight variability with mortality and major cardiovascular events among individuals with type 2 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Weight management is strongly promoted for overweight or obese patients with type 2 diabetes (T2DM) by current guidelines. However, the prognostic impact of weight loss achieved without behavioural intervention on the mortality and cardiovascular (CV) outcomes in diabetic patients is still contested. METHODS: We searched the PubMed, Embase, and Cochrane Library databases for studies that investigated the association of weight loss or weight variability with mortality and CV outcomes. Results of studies that measured weight loss by percentage weight loss from baseline and stratified it as > 10% and 5-10% or studies that computed weight variability were pooled using random effects model. Study quality was evaluated using the Newcastle-Ottawa Scale. RESULTS: Thirty eligible studies were included in the systematic review and 13 of these were included in the meta-analysis. Large weight loss (> 10%) was associated with increased risk of all-cause mortality (pooled hazard ratio (HR) 2.27, 95% CI 1.51-3.42), composite of major CV events (pooled HR 1.71, 95% CI 1.38-2.12) and CV mortality (pooled HR 1.50, 95% CI 1.27-1.76) among T2DM patients. Moderate weight loss showed no significant association with all-cause mortality (pooled HR 1.17, 95% CI 0.97-1.41) or CV outcomes (pooled HR 1.12, 95% CI 0.94-1.33). Weight variability was associated with high hazard of all-cause mortality (pooled HR 1.54, 95% CI 1.52-1.56). CONCLUSIONS: Large weight loss and large fluctuations in weight are potential markers of increased risk of mortality and CV events in T2DM patients. Maintaining a stable weight may have positive impact in these patients.

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.

Impact of Type 2 Diabetes Mellitus on Epicardial Adipose Tissue and Myocardial Microcirculation by MRI in Postmenopausal Women.

BACKGROUND: Type 2 diabetes mellitus (T2DM) often occurs conjunctly with the menopausal transition in female patients. In addition, epicardial adipose tissue (EAT) has an unfavorable impact on the myocardium and coronary arteries under the influence of metabolic disorders. PURPOSE: To investigate the impact of T2DM on EAT and myocardial microvascular function in postmenopausal women. STUDY TYPE: Retrospective. POPULATION: One-hundred sixty-one postmenopausal women divided into three groups: newly diagnosed (≤5 years) T2DM (n = 56, 58.6 ± 7.7 years), long-term (>5 years) T2DM (n = 57, 61.9 ± 7.9 years), and healthy controls (n = 48, 59.4 ± 7.4 years). FIELD STRENGTH/SEQUENCE: 3.0 T; balanced steady-state free precession and inversion recovery prepared echo-planar sequences. ASSESSMENT: EAT volume was quantified by delineating the epicardial border and the visceral layer of pericardium on the short-axis cine stacks. Perfusion parameters including upslope, maximum signal intensity (MaxSI) and time to maximum signal intensity (TTM) were derived from the first-pass perfusion signal intensity-time curves. STATISTICAL TESTS: One-way analysis of variance, Pearson's and Spearman correlation, and multivariable linear regression. Two-sided P < 0.05 was considered statistically significant. RESULTS: EAT volume was significantly increased in diabetic postmenopausal women compared to the controls (48.4 ± 13.4 mL/m2 [newly diagnosed T2DM] vs. 58.4 ± 17.3 mL/m2 [long-term T2DM] vs. 35.8 ± 12.3 mL/m2 [controls]). Regarding perfusion parameters, upslope and MaxSI were significantly reduced (2.6 ± 1.0 [newly diagnosed T2DM] vs. 2.1 ± 0.8 [long-term T2DM] vs. 3.6 ± 1.3 [controls]; and 21.4 ± 6.9 [newly diagnosed T2DM] vs. 18.7 ± 6.4 [long-term T2DM] vs. 28.4 ± 8.6 [controls]), whereas TTM was significantly increased in the T2DM groups compared to the control group (23.6 ± 8.7 [newly diagnosed T2DM] vs. 27.1 ± 9.4 [long-term T2DM] vs. 21.4 ± 6.0 [controls]). Multivariable analysis (adjusted coefficient of determination [R2 ] = 0.489) showed that EAT volume (ß = -0.610) and menopausal age (ß = 0.433) were independently correlated with decreased perfusion upslope. DATA CONCLUSION: Diabetic postmenopausal women had significantly higher EAT volume and more impaired microcirculation compared to the controls. Increased EAT volume and earlier menopausal age were independently associated with microvascular dysfunction in these patients. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.