Glycemic control and clinical outcomes in diabetic patients with heart failure and reduced ejection fraction: insight from ventricular remodeling using cardiac MRI.

BACKGROUND: Glycemic control, as measured by glycosylated hemoglobin (HbA1c), is an important biomarker to evaluate diabetes severity and is believed to be associated with heart failure development. Type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) commonly coexist, and the combination of these two diseases indicates a considerably poorer outcome than either disease alone. Therefore, glycemic control should be carefully managed. The present study aimed to explore the association between glycemic control and clinical outcomes, and to determine the optimal glycemic target in this specific population. METHODS: A total of 262 patients who underwent cardiac MRI were included and were split by HbA1c levels [HbA1c < 6.5% (intensive control), HbA1c 6.5-7.5% (modest control), and HbA1c > 7.5% (poor control)]. The biventricular volume and function, as well as left ventricular (LV) systolic strains in patients in different HbA1c categories, were measured and compared. The primary and secondary outcomes were recorded. The association of different HbA1c levels with adverse outcomes was assessed. RESULTS: Despite similar biventricular ejection fractions, both patients with intensive and poor glycemic control exhibited prominent deterioration of LV systolic strain in the longitudinal component (P = 0.004). After a median follow-up of 35.0 months, 55 patients (21.0%) experienced at least one confirmed endpoint event. Cox multivariable analysis indicated that both patients in the lowest and highest HbA1c categories exhibited a more than 2-fold increase in the risk for primary outcomes [HbA1c < 6.5%: hazard ratio (HR) = 2.42, 95% confidence interval (CI) = 1.07-5.45; P = 0.033; HbA1c > 7.5%: HR = 2.24, 95% CI = 1.01-4.99; P = 0.038] and secondary outcomes (HbA1c < 6.5%: HR = 2.84, 95% CI = 1.16-6.96; P = 0.022; HbA1c > 7.5%: HR = 2.65, 95% CI = 1.08-6.50; P = 0.038) compared with those in the middle HbA1c category. CONCLUSIONS: We showed a U-shaped association of glycemic control with clinical outcomes in patients with T2DM and HFrEF, with the lowest risk of adverse outcomes among patients with modest glycemic control. HbA1c between 6.5% and 7.5% may be served as the optimal hypoglycemic target in this specific population.

Early left ventricular microvascular dysfunction in diabetic pigs: a longitudinal quantitative myocardial perfusion CMR study.

BACKGROUND: Microvascular pathology is one of the main characteristics of diabetic cardiomyopathy; however, the early longitudinal course of diabetic microvascular dysfunction remains uncertain. This study aimed to investigate the early dynamic changes in left ventricular (LV) microvascular function in diabetic pig model using the cardiac magnetic resonance (CMR)-derived quantitative perfusion technique. METHODS: Twelve pigs with streptozotocin-induced diabetes mellitus (DM) were included in this study, and longitudinal CMR scanning was performed before and 2, 6, 10, and 16 months after diabetic modeling. CMR-derived semiquantitative parameters (upslope, maximal signal intensity, perfusion index, and myocardial perfusion reserve index [MPRI]) and fully quantitative perfusion parameters (myocardial blood flow [MBF] and myocardial perfusion reserve [MPR]) were analyzed to evaluate longitudinal changes in LV myocardial microvascular function. Pearson correlation was used to analyze the relationship between LV structure and function and myocardial perfusion function. RESULTS: With the progression of DM duration, the upslope at rest showed a gradually increasing trend (P = 0.029); however, the upslope at stress and MBF did not change significantly (P > 0.05). Regarding perfusion reserve function, both MPRI and MPR showed a decreasing trend with the progression of disease duration (MPRI, P = 0.001; MPR, P = 0.042), with high consistency (r = 0.551, P < 0.001). Furthermore, LV MPR is moderately associated with LV longitudinal strain (r = - 0.353, P = 0.022), LV remodeling index (r = - 0.312, P = 0.033), fasting blood glucose (r = - 0.313, P = 0.043), and HbA1c (r = - 0.309, P = 0.046). Microscopically, pathological results showed that collagen volume fraction increased gradually, whereas no significant decrease in microvascular density was observed with the progression of DM duration. CONCLUSIONS: Myocardial microvascular reserve function decreased gradually in the early stage of DM, which is related to both structural (but not reduced microvascular density) and functional abnormalities of microvessels, and is associated with increased blood glucose, reduced LV deformation, and myocardial remodeling.

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.

Free-Breathing Compressed Sensing Cine Cardiac MRI for Assessment of Left Ventricular Strain by Feature Tracking in Children.

BACKGROUND: Cardiac MRI feature-tracking (FT) with breath-holding (BH) cine balanced steady state free precession (bSSFP) imaging is well established. It is unclear whether FT-strain measurements can be reliably derived from free-breathing (FB) compressed sensing (CS) bSSFP imaging. PURPOSE: To compare left ventricular (LV) strain analysis and image quality of an FB CS bSSFP cine sequence with that of a conventional BH bSSFP sequence in children. STUDY TYPE: Prospective. SUBJECTS: 40 children able to perform BHs (cohort 1 [12.1 ± 2.2 years]) and 17 children unable to perform BHs (cohort 2 [5.2 ± 1.8 years]). FIELD STRENGTH/SEQUENCE: 3T, bSSFP sequence with and without CS. ASSESSMENT: Acquisition times and image quality were assessed. LV myocardial deformation parameters were compared between BH cine and FB CS cine studies in cohort 1. Strain indices and image quality of FB CS cine studies were also assessed in cohort 2. Intraobserver and interobserver variability of strain parameters was determined. STATISTICAL TESTS: Paired t-test, Wilcoxon signed-rank test, intraclass correlation coefficient (ICC), and Bland-Altman analysis. A P-value <0.05 was considered statistically significant. RESULTS: In cohort 1, the mean acquisition time of the FB CS cine study was significantly lower than for conventional BH cine study (15.6 s vs. 209.4 s). No significant difference were found in global circumferential strain rate (P = 0.089), global longitudinal strain rate (P = 0.366) and EuroCMR image quality scores (P = 0.128) between BH and FB sequences in cohort 1. The overall image quality score of FB CS cine in cohort 2 was 3.5 ± 0.5 with acquisition time of 14.7 ± 2.1 s. Interobserver and intraobserver variabilities were good to excellent (ICC = 0.810 to 0.943). DATA CONCLUSION: FB CS cine imaging may be a promising alternative technique for strain assessment in pediatric patients with poor BH ability. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Association of Pulmonary Transit Time and Pulmonary Blood Volume From First-Pass Perfusion Cardiac MRI With Diastolic Dysfunction and Left Ventricle Deformation in Restrictive Cardiomyopathy.

BACKGROUND: Patients with restrictive cardiomyopathy (RCM) have impaired diastolic filling and hemodynamic congestion. Pulmonary transit time (PTT) and pulmonary blood volume index (PBVi) reflect the hemodynamic status, but the relationship with left ventricle (LV) dysfunction remains unclear. PURPOSE: To evaluate the PTT and PBVi in RCM patients, the association with diastolic dysfunction and LV deformation, and the effects on the occurrence of major adverse cardiac events (MACE) in RCM patients. STUDY TYPE: Retrospective. POPULATION: 137 RCM patients (88 men, age 58.80 ± 10.83 years) and 68 age- and sex-matched controls (46 men, age 57.00 ± 8.59 years). FIELD STRENGTH/SEQUENCE: 3.0T/Balanced steady-state free precession sequence, recovery prepared echo-planar imaging sequence, and phase-sensitive inversion recovery sequence. ASSESSMENT: The LV function and peak strain (PS) parameters were measured. The PTT was calculated and corrected by heart rate (PTTc). The PBVi was calculated as the product of PTTc and RV stroke volume index. STATISTICAL TESTS: Chi-squared test, student's t-test, Mann-Whitney U test, Pearson's or Spearman's correlation, multivariate linear regression, Kaplan-Meier survival analysis, and Cox regression models analysis. A P-value <0.05 was considered statistically significant. RESULTS: The PTTc showed a significant correlation with the E/A ratio (r = 0.282), and PBVi showed a significant correlation with the E/e' ratio, E/A ratio, and diastolic dysfunction stage (r = 0.222, 0.320, and 0.270). PTTc showed an independent association with LVEF, LV circumferential PS, and LV longitudinal PS (ß = 0.472, 0.299, and 0.328). In Kaplan-Meier analysis, higher PTTc and PBVi were significantly associated with MACE. In multivariable Cox regression analysis, PTTc was a significantly independent predictor of the MACE in combination with both cardiac MRI functional and tissue parameters (hazard ratio: 1.23/1.32, 95% confidence interval: 1.10-1.42/1.20-1.46). DATA CONCLUSION: PTTc and PBVi are associated with diastolic dysfunction and deteriorated LV deformation, and PTTc independently predicts MACE in patients with RCM. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Left ventricular concentric hypertrophy with cardiac magnetic resonance imaging improves risk stratification in patients with Duchenne muscular dystrophy: a prospective cohort study.

BACKGROUND: The development of left ventricular (LV) remodeling has been associated with an increased cardiovascular risk and cardiogenic death, and different patterns of remodeling result in varying levels of prognosis. OBJECTIVE: To investigate the association between different patterns of LV remodeling and clinical outcomes in the preclinical stage of patients with Duchenne muscular dystrophy (DMD). MATERIALS AND METHODS: A total of 148 patients with DMD and 43 sex- and age-matched healthy participants were enrolled. We used the four-quadrant analysis method to investigate LV remodeling based on cardiac magnetic resonance (MR) imaging. Kaplan-Meier curves were generated to illustrate the event-free survival probability stratified by the LV remodeling pattern. Cox regression models were constructed and compared to evaluate the incremental predictive value of the LV remodeling pattern. RESULTS: During the median follow-up period of 2.2 years, all-cause death, cardiomyopathy, and ventricular arrhythmia occurred in 5, 35, and 7 patients, respectively. LV concentric hypertrophy (hazard ratio 2.91, 95% confidence interval 1.47-5.75, P=0.002) was an independent predictor of composite endpoint events. Compared to the model without LV concentric hypertrophy, the model with LV concentric hypertrophy had significant incremental predictive value (chi-square value 33.5 vs. 25.2, P=0.004). CONCLUSION: Age and late gadolinium enhancement positivity were positively correlated with clinical outcomes according to the prediction models. LV concentric hypertrophy was also an independent predictor for risk stratification and provided incremental value for predicting clinical outcomes in the preclinical stage of patients with DMD.

Association of diabetes mellitus and glycemic control with left ventricular function and deformation in patients after acute myocardial infarction: a 3 T cardiac magnetic resonance study.

BACKGROUND: Diabetes mellitus (DM) is considered a major risk factor for myocardial infarction (MI), and MI patients with DM have a poor prognosis. Accordingly, we aimed to investigate the additive effects of DM on LV deformation in patients after acute MI. MATERIALS AND METHODS: One hundred thirteen MI patients without DM [MI (DM-)], 95 with DM [MI (DM+)] and 71 control subjects who underwent CMRscanning were included. LV function, infarct size and LV global peak strains in the radial, circumferential and longitudinal directions were measured. MI (DM+) patients were divided into two subgroups based on the HbA1c level (< 7.0% and ≥ 7.0%). The determinants of reduced LV global myocardial strain for all MI patients and MI (DM+) patients were assessed using multivariable linear regression analyses. RESULTS: Compared with control subjects, both MI (DM-) and MI (DM+) patients presented higher LV end-diastolic and end-systolic volume index and lower LV ejection fraction. LV global peak strains progressively declined from the control group to the MI(DM-) group to the MI(DM+) group (all p < 0.05). Subgroup analysis showed that LV global radial PS and longitudinal PS were worse in MI(MD+) patients with poor glycemic control than in those with good glycemic control (all p < 0.05). DM was an independent determinant of impaired LV global peak strain in radial, circumferential and longitudinal directions in patients after acute MI (ß = - 0.166, 0.164 and 0.262, both p < 0.05). The HbA1c level was independently associated with a decreased LV global radial PS (ß = - 0.209, p = 0.025) and longitudinal PS (ß = 0.221, p = 0.010) in MI (DM+) patients. CONCLUSIONS: DM has an additive deleterious effect on LV function and deformation in patients after acute MI, and HbA1c was independently associated with impaired LV myocardial strain.

Early longitudinal changes in left ventricular function and morphology in diabetic pigs: evaluation by 3.0T magnetic resonance imaging.

BACKGROUND: Previous researches on large animal models of diabetic cardiomyopathy were insufficient. The aim of this study was to evaluate early changes in left ventricular (LV) function and morphology in diabetic pigs using a cardiac magnetic resonance (CMR) time-volume curve and feature tracking technique. METHODS: Streptozotocin (STZ) was used to induce diabetic in sixteen pigs. 3.0T MRI scanned the pig's heart before and 2, 6, 10 and 16 months after modelling. CMR biomarkers, including time-volume curve and myocardial strain, were compared to analyse the longitudinal changes in LV function and morphology. Pearson correlation was used to evaluate the relationship between LV strain and remodelling. Cardiac specimens were obtained at 6, 10, and 16 months after modelling to observe the myocardial ultrastructural and microstructure at different courses of diabetes. RESULTS: Twelve pigs developed diabetes. The 80% diastolic volume recovery rate (DVR) at 6 months after modelling was significantly higher than that before modelling (0.78 ± 0.08vs. 0.67 ± 0.15). The LV global longitudinal peak strain (GLPS) (- 10.21 ± 3.15 vs. - 9.74 ± 2.78 vs. - 9.38 ± 3.71 vs. - 8.71 ± 2.68 vs. - 6.59 ± 2.90%) altered gradually from the baseline data to 2, 6, 10 and 16 months after modelling. After 16 months of modelling, the LV remodelling index (LVRI) of pigs increased compared with that before modelling (2.19 ± 0.97 vs. 1.36 ± 0.45 g/ml). The LVRI and myocardial peak strain were correlated in diabetic pigs (r= - 0.40 to - 0.54), with GLPS being the most significant. Electron microscopy and Masson staining showed that myocardial damage and fibrosis gradually increased with the progression of the disease. CONCLUSION: Intravenous injection of STZ can induce a porcine diabetic cardiomyopathy model, mainly characterized by decreased LV diastolic function and strain changes accompanied by myocardial remodelling. The changes in CMR biomarkers could reflect the early myocardial injury of diabetic cardiomyopathy.

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.

Effects of diabetes mellitus on left ventricular function and deformation in patients with restrictive cardiomyopathies: a 3.0T CMR feature tracking study.

BACKGROUND: Diabetes mellitus (DM) is the most common metabolic disease worldwide and a major risk factor for adverse cardiovascular events, while the additive effects of DM on left ventricular (LV) deformation in the restrictive cardiomyopathy (RCM) cohort remain unclear. Accordingly, we aimed to investigate the additive effects of DM on LV deformation in patients with RCM. MATERIALS AND METHODS: One hundred thirty-six RCM patients without DM [RCM(DM-)], 46 with DM [RCM (DM+)], and 66 age- and sex-matched control subjects who underwent cardiac magnetic resonance (CMR) scanning were included. LV function, late gadolinium enhancement (LGE) type, and LV global peak strains (including radial, circumferential, and longitudinal directions) were measured. The determinant of reduced LV global myocardial strain for all RCM patients was assessed using multivariable linear regression analyses. The receiver operating characteristic curve (ROC) was performed to illustrate the relationship between DM and decreased LV deformation. RESULTS: Compared with the control group, RCM (DM-) and RCM(DM+) patients presented increased LV end-diastolic index and end-systolic volume index and decreased LV ejection fraction. LV GPS in all three directions and longitudinal PDSR progressively declined from the control group to the RCM(DM-) group to the RCM(DM+) group (all p < 0.05). DM was an independent determinant of impaired LV GPS in the radial, circumferential, and longitudinal directions and longitudinal PDSR (ß = - 0.217, 0.176, 0.253, and - 0.263, all p < 0.05) in RCM patients. The multiparameter combination, including DM, showed an AUC of 0.81(95% CI 0.75-0.87) to predict decreased LV GLPS and an AUC of 0.69 (95% CI 0.62-0.76) to predict decreased LV longitudinal PDSR. CONCLUSIONS: DM may have an additive deleterious effect on LV dysfunction in patients with RCM, especially diastolic dysfunction in RCM patients, indicating the importance of early identification and initiation of treatment of DM in patients with RCM.

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.

Effect of Obesity on Left Ventricular Remodeling and Clinical Outcome in Chinese Patients With Hypertrophic Cardiomyopathy: Assessed by Cardiac MRI.

BACKGROUND: Obesity is highly prevalent in patients with hypertrophic cardiomyopathy (HCM) and believed to influence its phenotype. PURPOSE: To explore the effects of obesity on left ventricular (LV) remodeling and long-term clinical course in Chinese patients with HCM. STUDY TYPE: Longitudinal. POPULATION: A total of 247 patients with HCM classified according to body mass index (BMI) (normal weight: BMI = 18.0-22.9 kg/m2 [N = 90]; overweight: BMI = 23.0-24.9 kg/m2 [N = 58]; and obese: BMI ≥ 25 kg/m2 [N = 99]). FIELD STRENGTH/SEQUENCE: 3.0 T/Balanced steady-state free precession sequence and phase-sensitive inversion recovery late gadolinium enhancement (LGE) sequence. ASSESSMENT: LV function and geometry were measured. LV peak strain analysis was performed. The presence and percentage of LGE in the LV were recorded. The endpoints including heart failure, sudden cardiac death, and overall composite outcome were assessed during a median follow-up of 4.1 years (interquartile range, 3.0-6.2 years). STATISTICAL TESTS: One-way analysis of variance, Kruskal-Wallis test, or chi-square test; Pearson correlation coefficient (r); multivariable linear regression analysis; Kaplan-Meier survival analysis; and Cox proportional hazards model analysis were conducted. A two-tailed P-value < 0.05 was considered statistically significant. RESULTS: Obese patients exhibited a significant progressive increase in LV mass compared with normal-weight patients. The magnitude of all LV strain indices gradually and significantly decreased as BMI increased, whereas LV ejection fraction was not significantly different among BMI groups (P = 0.364). Multivariable linear regression analysis showed that obesity had a significant association with impaired strain indices as well as with indexed LV mass. Multivariable Cox model analysis retained obesity as an independent marker for future endpoints, and conveyed a > 3-fold increase in risk compared with patients with normal weight (hazard ratio, 3.04; 95% confidence interval, 1.07-6.57). DATA CONCLUSION: Obesity is an important environmental modifier that is associated with adverse LV remodeling and is independently associated with future clinical outcomes in Chinese patients with HCM. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Incremental prognostic value of myocardial strain over ventricular volume in patients with repaired tetralogy of Fallot.

OBJECTIVES: The relative incremental predictive value of myocardial deformation over ventricular volume for future adverse events in patients with repaired tetralogy of Fallot (rTOF) remains unknown. We aimed to determine the incremental prognostic value of myocardial deformation over ventricular volume to predict adverse events in patients with rToF. METHODS: We retrospectively included patients with rTOF who completed cardiac magnetic resonance (CMR) and follow-up in our hospital from January 2014 to October 2020, and stratified according to the presence or absence of adverse events during follow-up. The strain parameters of the right ventricular (RV) and left ventricular (LV) were obtained from CMR-derived feature tracking. Multivariable Cox proportional hazard models and net reclassification improvement analysis were used to analyze the prognostic information of biventricular strain and volume parameters in rTOF patients. RESULTS: Among 98 patients with rTOF, 54 (55.1%) experienced primary and/or secondary events during a median follow-up period of 27.0 months. Univariable analysis indicated that RV volume and strain were significantly associated with both primary events and all adverse events (all p < .01). Multivariable Cox regression and net reclassification improvement analyses achieved incremental global χ2 (all p < .001), C index (all p < .001), and overall correct reclassification by sequentially adding CMR-derived RV volume, RV strain and LV strain parameters to preexisting clinical factors in adverse events model analyses. CONCLUSIONS: RV and LV myocardial deformation provided incremental prognostic information and significant improvement for risk stratification over RV size and clinical variables and therefore can be combined to further enhance prognostication. KEY POINTS: • RV volume and strain were significantly associated with both primary events and all adverse events, whereas LV volume and strain were associated with primary events. • Ventricular myocardial deformation is a strong predictor of adverse outcomes of patients with repaired tetralogy of Fallot, providing increased prognostic information and significantly improved risk stratification over ventricular size.

Clinical utilisation of multimodal quantitative magnetic resonance imaging in investigating muscular damage in Duchenne muscular dystrophy: a study on the association between gluteal muscle groups and motor function.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disease characterised by progressive muscular weakness and atrophy. Currently, studies on DMD muscle function mostly focus on individual muscles; little is known regarding the effect of gluteal muscle group damage on motor function. OBJECTIVE: To explore potential imaging biomarkers of hip and pelvic muscle groups for measuring muscular fat replacement and inflammatory oedema in DMD with multimodal quantitative magnetic resonance imaging (MRI). MATERIALS AND METHODS: One hundred fifty-nine DMD boys and 32 healthy male controls were prospectively included. All subjects underwent MRI examination of the hip and pelvic muscles with T1 mapping, T2 mapping and Dixon sequences. Quantitatively measured parameters included longitudinal relaxation time (T1), transverse relaxation time (T2) and fat fraction. Investigations were all based on hip and pelvic muscle groups covering flexors, extensors, adductors and abductors. The North Star Ambulatory Assessment and stair climbing tests were used to measure motor function in DMD. RESULTS: T1 of the extensors (r = 0.720, P < 0.01), flexors (r = 0.558, P < 0.01) and abductors (r = 0.697, P < 0.001) were positively correlated with the North Star Ambulatory Assessment score. In contrast, T2 of the adductors (r = -0.711, P < 0.01) and fat fraction of the extensors (r = -0.753, P < 0.01) were negatively correlated with the North Star Ambulatory Assessment score. Among them, T1 of the abductors (b = 0.013, t = 2.052, P = 0.042), T2 of the adductors (b = -0.234, t = -2.554, P = 0.012) and fat fraction of the extensors (b = -0.637, t = - 4.096, P < 0.001) significantly affected the North Star Ambulatory Assessment score. Moreover, T1 of the abductors was highly predictive for identifying motor dysfunction in DMD, with an area under the curve of 0.925. CONCLUSION: Magnetic resonance biomarkers of hip and pelvic muscle groups (particularly T1 values of the abductor muscles) have the potential to be used as independent risk factors for motor dysfunction in DMD.

Longitudinal changes in magnetic resonance imaging biomarkers of the gluteal muscle groups and functional ability in Duchenne muscular dystrophy: a 12-month cohort study.

BACKGROUND: Quantitative magnetic resonance imaging (MRI) is considered an objective biomarker of Duchenne muscular dystrophy (DMD), but the longitudinal progression of MRI biomarkers in gluteal muscle groups and their predictive value for future motor function have not been described. OBJECTIVE: To explore MRI biomarkers of the gluteal muscle groups as predictors of motor function decline in DMD by characterizing the progression over 12 months. MATERIALS AND METHODS: A total of 112 participants with DMD were enrolled and underwent MRI examination of the gluteal muscles to determine fat fraction and longitudinal relaxation time (T1). Investigations were based on gluteal muscle groups including flexors, extensors, adductors, and abductors. The North Star Ambulatory Assessment and timed functional tests were performed. All participants returned for follow-up at an average of 12 months and were divided into two subgroups (functional stability/decline groups) based on changes in timed functional tests. Univariable and multivariable logistic regression methods were used to explore the risk factors associated with future motor function decline. RESULTS: For the functional decline group, all T1 values decreased, while fat fraction values increased significantly over 12 months (P<0.05). For the functional stability group, only the fat fraction of the flexors and abductors increased significantly over 12 months (P<0.05). The baseline T1 value was positively correlated with North Star Ambulatory Assessment and negatively correlated with timed functional tests at the 12-month follow-up (P<0.001), while the baseline fat fraction value was negatively correlated with North Star Ambulatory Assessment and positively correlated with timed functional tests at the 12-month follow-up (P<0.001). Multivariate regression showed that increased fat fraction of the abductors was associated with future motor function decline (model 1: odds ratio [OR]=1.104, 95% confidence interval [CI]: 1.026~1.187, P=0.008; model 2: OR=1.085, 95% CI: 1.013~1.161, P=0.019), with an area under the curve of 0.874. CONCLUSION: Fat fraction of the abductors is a powerful predictor of future motor functional decline in DMD patients at 12 months, underscoring the importance of focusing early on this parameter in patients with DMD.

Inflammation in Remote Myocardium and Left Ventricular Remodeling After Acute Myocardial Infarction: A Pilot Study Using T2 Mapping.

BACKGROUND: The pathophysiological changes in the remote myocardium after acute myocardial infarction (MI) remains less understood. PURPOSE: To assess the inflammation in the remote myocardium post-MI and its association with left ventricular (LV) remodeling using T2 mapping. STUDY TYPE: Prospective. ANIMAL MODEL AND SUBJECTS: Twelve pigs at 3-day post-MI, 6 pigs at 3-month post-MI, 6 healthy pigs; 54 patients at 3-day and 3-month post-MI, 31 healthy volunteers; FIELD STRENGTH/SEQUENCE: A 3 T MRI/ steady-state free-precession sequence for T2 mapping (animals: 0, 30, and 55 msec; human: 0, 25, and 55 msec), phase-sensitive inversion recovery gradient echo for late gadolinium enhancement (LGE), balanced steady free-precession sequence for cine. ASSESSMENT: Infarcted myocardium was defined on LGE, remote T2 was measured on T2 maps. LV remodeling was evaluated as LV end-diastolic volume change index between two scans using cine. CD68 staining was conducted to detect monocyte/macrophage. STATISTICAL TESTS: Student-t test and one-way ANOVA were used to compare remote T2 with normal controls. The association of remote T2 with LV remodeling was assessed using linear regression. P values of <0.05 were used to denote statistical significance. RESULTS: Compared with healthy pigs, remote T2 significantly increased from 3 days to 3 months post-MI (31.43 ± 0.67 vs. 33.53 ± 1.15 vs. 36.43 ± 1.07 msec). CD68 staining demonstrated the inflammation in remote myocardium post-MI but not in healthy pigs. Significant remote myocardial alterations in T2 were also observed in human group (40.51 ± 1.79 vs. 41.94 ± 1.14 vs. 42.52 ± 1.71 msec). In patients, the 3-month remote T2 (ß = 0.432) and remote T2 variation between two scans (ß = 0.554) were both independently associated with LV remodeling. CONCLUSION: T2 mapping could characterize the abnormalities in the remote myocardium post-MI, which was potentially caused by the inflammatory response. Moreover, variations in remote T2 were associated with LV remodeling. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

Impact of myocardial scars on left ventricular deformation in type 2 diabetes mellitus after myocardial infarction by contrast-enhanced cardiac magnetic resonance.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major risk factor for coronary artery disease and myocardial infarction (MI). The interaction of diabetic cardiomyopathy and MI scars on myocardial deformation in T2DM patients is unclear. Therefore, we aimed to evaluate myocardial deformation using cardiac magnetic resonance (CMR) in T2DM patients with previous MI and investigated the influence of myocardial scar on left ventricular (LV) deformation. METHODS: Overall, 202 T2DM patients, including 46 with MI (T2DM(MI+)) and 156 without MI (T2DM(MI-)), and 59 normal controls who underwent CMR scans were included. Myocardial scars were assessed by late gadolinium enhancement. LV function and deformation, including LV global function index, LV global peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR), were compared among these groups. Correlation and multivariate linear regression analyses were used to investigate the relationship between myocardial scars and LV deformation. RESULTS: Decreases were observed in LV function and LV global PS, PSSR, and PDSR in the T2DM(MI+) group compared with those of the other groups. Reduced LV deformation (p < 0.017) was observed in the T2DM(MI+) group with anterior wall infarction. The increased total LV infarct extent and infarct mass of LV were related to decreased LV global PS (radial, circumferential, and longitudinal directions; p < 0.01) and LV global PSSR (radial and circumferential directions, p < 0.02). Multivariate analysis demonstrated that NYHA functional class and total LV infarct extent were independently associated with LV global radial PS (ß = - 0.400 and ß = - 0.446, respectively, all p < 0.01; model R2 = 0.37) and circumferential PS (ß = 0.339 and ß = 0.530, respectively, all p < 0.01; model R2 = 0.41), LV anterior wall infarction was independently associated with LV global longitudinal PS (ß = 0.398, p = 0.006). CONCLUSIONS: The myocardial scarring size in T2DM patients after MI is negatively correlated with LV global PS and PSSR, particularly in the circumferential direction. Additionally, different MI regions have different effects on the reduction of LV deformation, and relevant clinical evaluations should be strengthened.

Myocardial perfusion assessment in the infarct core and penumbra zones in an in-vivo porcine model of the acute, sub-acute, and chronic infarction.

OBJECTIVES: To assess the longitudinal changes of microvascular function in different myocardial regions after myocardial infarction (MI) using myocardial blood flow derived by dynamic CT perfusion (CTP-MBF), and compare CTP-MBF with the results of cardiac magnetic resonance (CMR) and histopathology. METHODS: The CTP scanning was performed in a MI porcine model 1 day (n = 15), 7 days (n = 10), and 3 months (n = 5) following induction surgery. CTP-MBF was measured in the infarcted myocardium, penumbra, and remote myocardium, respectively. CMR perfusion and histopathology were performed for validation. RESULTS: From baseline to follow-up scans, CTP-MBF presented a stepwise increase in the infarcted myocardium (68.51 ± 11.04 vs. 86.73 ± 13.32 vs. 109.53 ± 26.64 ml/100 ml/min, p = 0.001) and the penumbra (104.92 ± 29.29 vs. 120.32 ± 24.74 vs. 183.01 ± 57.98 ml/100 ml/min, p = 0.008), but not in the remote myocardium (150.05 ± 35.70 vs. 166.66 ± 38.17 vs. 195.36 ± 49.64 ml/100 ml/min, p = 0.120). The CTP-MBF correlated with max slope (r = 0.584, p < 0.001), max signal intensity (r = 0.357, p < 0.001), and time to max (r = - 0.378, p < 0.001) by CMR perfusion. Moreover, CTP-MBF defined the infarcted myocardium on triphenyl tetrazolium chloride staining (AUC: 0.810, p < 0.001) and correlated with microvascular density on CD31 staining (r = 0.561, p = 0.002). CONCLUSION: CTP-MBF could quantify the longitudinal changes of microvascular function in different regions of the post-MI myocardium, which demonstrates good agreement with contemporary CMR and histopathological findings. KEY POINTS: • The CT perfusion-based myocardial blood flow (CTP-MBF) could quantify the microvascular impairment in different myocardial regions after myocardial infarction (MI) and track its recovery over time. • The assessment of CTP-MBF is in good agreement with contemporary cardiac MRI and histopathological findings, which potentially facilitates a rapid approach for pathophysiological insights following MI.

Global, segmental and layer specific analysis of myocardial involvement in Duchenne muscular dystrophy by cardiovascular magnetic resonance native T1 mapping.

BACKGROUND: Progressive cardiomyopathy accounts for almost all mortality among Duchenne muscular dystrophy (DMD) patients.| Thus, our aim was to comprehensively characterize myocardial involvement by investigating the heterogeneity of native T1 mapping in DMD patients using global and regional (including segmental and layer-specific) analysis across a large cohort. METHODS: We prospectively enrolled 99 DMD patients (8.8 ± 2.5 years) and 25 matched male healthy controls (9.5 ± 2.5 years). All subjects underwent cardiovascular magnetic resonance (CMR) with cine, T1 mapping and late gadolinium enhancement (LGE) sequences. Native T1 values based on the global and regional myocardium were measured, and LGE was defined. RESULTS: LGE was present in 49 (49%) DMD patients. Global native T1 values were significantly longer in LGE-positive (LGE +) patients than in healthy controls, both in basal slices (1304 ± 55 vs. 1246 ± 27 ms, p < 0.001) and in mid-level slices (1305 ± 57 vs. 1245 ± 37 ms, p < 0.001). No significant difference in global native T1 was found between healthy controls and LGE-negative (LGE-) patients. In segmental analysis, LGE + patients had significantly increased native T1 in all analyzed segments compared to the healthy control group. Meanwhile, the comparison between LGE- patients and healthy controls showed significantly elevated values only in the basal anterolateral segment (1273 ± 62 vs. 1234 ± 40 ms, p = 0.034). Interestingly, the epicardial layer had a significantly higher native T1 in LGE- patients than in healthy controls (p < 0.05), whereas no such pattern was noticed in the global myocardium. Epicardial layer native T1 resulted in the highest diagnostic performance for distinguishing between healthy controls and DMD patients in receiver operating curve analyses (area under the curve [AUC] 0.84 for basal level and 0.85 for middle level) when compared to global native T1 and endocardial layer native T1. CONCLUSIONS: Myocardial regional native T1, particularly epicardial native T1, seems to have potential as a novel robust marker of very early cardiac involvement in DMD patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ) ChiCTR1800018340, 09/12/2018, Retrospectively registered.

Prognostic value of dual-source computed tomography (DSCT) angiography characteristics in anomalous coronary artery from the opposite sinus (ACAOS) patients: a large-scale retrospective study.

BACKGROUND: Most reported cases of right anomalous coronary artery from the opposite sinus (R-ACAOS) have benign clinical outcomes. However, patients with left ACAOS (L-ACAOS) and some of the patients with R-ACAOS are more at risk for arrhythmias and sudden cardiac death, which remains a major concern. Here we report the prevalence and anatomical features of ACAOS patients. Moreover, we explore the high-risk morphological signs and evaluate their mid-term prognostic value in R-ACAOS patients without surgical intervention. METHODS: Data from coronary computed tomography angiography (CTA) of 30,593 patients, pertaining to a single center over 5 consecutive years, were retrospectively analyzed. The image analysis included stenosis severity ranking and high-risk anatomy evaluation, based on the commercially available image post-processing software OsirX. Patients with R-ACAOS and without evidence of coronary atherosclerosis (CAD) were followed-up, with recording of the cardiovascular clinical events. Cox regression analysis was performed to identify the potential anatomical risk factors of cardiovascular clinical events for non-CAD R-ACAOS patients, using R project. RESULTS: The prevalence of ACAOS in the study population was 0.69% (211/30593). Significant differences were found between patients with mild (< 50%) and severe (> 50%) stenosis, in terms of height-to-weight ratio (HW ratio), take-off angle, and proximal stenosis length. A total of 54 cardiovascular clinical events were observed among 108 non-CAD R-ACAOS patients and an average follow-up of 27.8 ± 18.7 months. Among those patients' anatomical features, stenosis severity was the main risk factor for cardiovascular clinical events during the mid-term follow-up, with a risk ratio of 4.14 (95% CI: 1.78 to 9.63, P < 0.001). CONCLUSIONS: Among patients referred to coronary CTA, the overall incidence of ACAOS was 0.69%. For patients with R-ACAOS, severe stenosis was the independent risk factor of adverse clinical events in the mid-term follow-up, and positive clinical intervention might be needed to help them avoid the malignant clinical events.