Epicardial Adipose Tissue is Associated with Geometry Alteration and Diastolic Dysfunction in Prediabetic Cardiomyopathy.

BACKGROUND: Diastolic dysfunction and alterations in cardiac geometry are early indicators of diabetic cardiomyopathy. However, the association between cardiac changes across the glucose continuum and the contribution of epicardial adipose tissue (EAT) to these changes has not yet been investigated. PURPOSE: In this study, we aim to investigated the EAT on cardiac diastolic function and structural alterations along the diabetic continuum using cardiac magnetic resonance imaging (CMRI). METHODS: We enrolled individuals who were categorized into groups based on glucose tolerance status. Left ventricular structure and diastolic function were assessed using echocardiography and CMRI to determine the EAT, intramyocardial fat, and associated parameters. Multivariable logistic regression models were also used. RESULTS: In a study of 370 patients (209 normal glucose tolerance, 82 prediabetes, 79 diabetes), those with prediabetes and diabetes showed increased heart dimensions and diastolic dysfunction, including E/E' (the ratio of early mitral inflow velocity to mitral annular early diastolic velocity) (7.9±0.51 vs. 8.5±0.64 vs. 10.0±0.93, p=0.010), left atrial volume index (28.21±14.7 vs. 33.2±12.8 vs. 37.4±8.2 mL/m2, p<0.001), and left ventricular peak filling rate (4.46±1.75 vs. 3.61±1.55 vs. 3.20±1.30 mL/s, p<0.001). EAT significantly increased in prediabetes and diabetes (26.3±1.16 vs. 31.3±1.83 vs. 33.9±1.9 gm, p=0.001), while intramyocardial fat did not differ significantly. Prediabetes altered heart geometry, but not diastolic function (OR 1.22 [1.02-1.83], p=0.012; and 1.70 [0.79-3.68], p=0.135). Diabetes significantly affected both heart structure and diastolic function (OR 1.42 [1.11-1.97], p=0.032; and 2.56 [1.03-5.40], p=0.034) after adjusting for covariates. CONCLUSIONS: Elevated EAT was observed in patients with prediabetes and is associated with adverse alterations in cardiac structure and diastolic function, potentially serving as an underlying mechanism for the early onset of diabetic cardiomyopathy.

Differentiating the Prognostic Determinants of Myocardial Steatosis for Heart Failure With Preserved Ejection Fraction by Cardiac Magnetic Resonance Imaging.

Background Myocardial steatosis and fibrosis may play a role in the pathophysiology of heart failure with preserved ejection fraction. We therefore investigated the prognostic significance of epicardial fat (epicardial adipose tissue [EAT]) and myocardial diffuse fibrosis. Methods and Results Myocardial fibrosis, estimated as extracellular volume (ECV), and EAT were measured using cardiac magnetic resonance imaging in 163 subjects with heart failure with preserved ejection fraction. We also evaluated cardiac structure and diastolic and systolic function by echocardiography and cardiac magnetic resonance imaging. After 24 months' follow-up, 39 (24%) subjects had experienced cardiovascular events, including hospitalization for heart failure, acute coronary syndrome, and cardiovascular death. Median EAT and mean ECV were significantly higher in subjects with cardiovascular events than survivors (EAT, 35 [25-45] versus 31 [21-38], P=0.006 and ECV, 28.9±3.16% versus 27.2±3.56%, P=0.04). Subjects with high EAT (≥42 g) had increased risk of cardiovascular events (hazard ratio [HR], 2.528 [95% CI, 1.704-4.981]; P=0.032). High ECV (>29%) was also significantly associated with poorer outcomes (HR, 1.647 [95% CI, 1.263-2.548]; P=0.013). With respect to secondary end points, high EAT and high ECV were associated with increased risk of the incident acute coronary syndrome (HR, 1.982 [95% CI, 1.008-4.123]; P=0.049) and hospitalization for heart failure (HR, 1.789 [95% CI, 1.102-6.987]; P=0.033), respectively. Conclusions Our study suggested that increased epicardial fat and ECV detected by cardiac magnetic resonance imaging have an impact on cardiovascular prognosis, in particular acute coronary syndrome and hospitalization for heart failure, respectively.

Myocardial adipose deposition and the development of heart failure with preserved ejection fraction.

AIMS: It has been proposed that an increase of myocardial adiposity is related to left ventricular (LV) diastolic dysfunction. The specific roles of myocardial steatosis including epicardial fat and intramyocardial fat for diastolic function are unknown in those patients suffering heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF). This study aims to determine the complex relationship between myocardial adiposity in patients with HFrEF or HFpEF. METHODS AND RESULTS: Using cardiac magnetic resonance imaging (CMRI), myocardial steatosis was measured in 305 subjects (34 patients with HFrEF, 163 with HFpEF, and 108 non-HF controls). We also evaluated cardiac structure and diastolic and systolic function by echocardiography and CMRI. Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non-HF controls [intramyocardial fat content (%), 1.56 (1.26, 1.89) vs. 0.75 (0.50, 0.87) and 1.0 (0.79, 1.15), P < 0.05]. Intramyocardial fat amount (%) was higher in HFpEF women than in men [1.91% (1.17%, 2.32%) vs. 1.22 (0.87%, 2.02%), P = 0.01]. When estimated by CMRI (left ventricular peak filling rate), echocardiographic E/e' level, or left atrial volume index, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients, and this was independent of age, co-morbidities, body mass index, gender, and myocardial fibrosis (standardized coefficient: ß = -0.34, P = 0.03; ß = 0.29, P = 0.025; and ß = 0.25, P = 0.02, respectively). CONCLUSIONS: Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non-HF controls. Independent of risk factors or gender, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients.

Effect of Empagliflozin on Cardiac Function, Adiposity, and Diffuse Fibrosis in Patients with Type 2 Diabetes Mellitus.

Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, significantly improves cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that empagliflozin might have beneficial effects on cardiac function, structure, adiposity, and myocardial diffuse fibrosis. This prospective study enrolled 35 patients (48.6% men, age 63.5 ± 9.7 years) with type 2 diabetes mellitus (T2DM) from June 1, 2017, to November 31, 2018. The patients received an SGLT2 inhibitor (empagliflozin 25 or 12.5 mg/d) for 6 months in addition to stable oral hypoglycaemic treatment. All patients underwent cardiac magnetic resonance imaging (CMRI) before and after empagliflozin treatment. Left ventricular (LV) function and structure were quantified using cine CMRI. Cardiac adiposity was defined based on pericardial fat and intracardiac triglyceride contents, whereas myocardial diffuse fibrosis was indicated by extracellular volume (ECV). The statistical significance of parameter changes was assessed using paired t-test and stepwise multiple linear regression. There were no significant differences in LV function and structure changes. Cardiac adiposity and diffuse fibrosis indices were also not different before and after empagliflozin treatment. Concerning clinical parameters, only a significant decrease in systolic blood pressure (by 6.4 mmHg) was observed (p = 0.013). Stepwise multiple linear regression revealed that worse baseline MRI parameters were associated with better improvements. Intracardiac triglyceride content decrease was inversely associated with baseline intracardiac triglyceride content (p < 0.001). Pericardial fat changes were negatively correlated with baseline pericardial fat (p < 0.001) and ECV changes (p = 0.028). ECV changes were inversely associated with baseline ECV (p < 0.001), baseline LV ejection fraction (p < 0.001), and LV mass index changes (p = 0.020). This study demonstrated that 6 months of empagliflozin treatment did not significantly improve the LV function, structure, adiposity, and diffuse fibrosis in patients with T2DM. Further, the beneficial effects of empagliflozin treatment might be more evident in patients with worse baseline LV substrate and structure.

Combination of Plasma Biomarkers and Clinical Data for the Detection of Myocardial Fibrosis or Aggravation of Heart Failure Symptoms in Heart Failure with Preserved Ejection Fraction Patients.

Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by heart failure symptoms and structural change (including fibrosis). The relationship between novel biomarkers and the above components remains unclear. Methods: Seventy-seven HFpEF patients were recruited. All patients underwent echocardiography with tissue doppler imaging, cardiac magnetic resonance imaging (CMRI), and measurement of plasma inflammatory, remodelling, endothelial function, and heart failure biomarker levels. Myocardial fibrosis was defined by CMRI-extracellular volume. Forward conditional logistic regression was applied to demonstrate the determinants of myocardial fibrosis or heart failure symptoms. Results: The levels of growth differentiation factor, tissue inhibitor of metalloproteinase (TIMP)-1, galectin-3, and N-terminal pro b-type natriuretic peptide (NT-proBNP) were significantly higher in patients with more myocardial fibrosis. Matrix metalloproteinase-2 (MMP-2) and galectin-3 were independent markers of ECV. After adjusting for confounding factors, plasma galectin-3 and MMP-2 levels were correlated with myocardial fibrosis levels (odds ratio (OR): 1.05, 95% confidence interval (CI): 1.02 to 1.09, p = 0.005 and OR: 2.11, 95% CI: 1.35⁻3.28, respectively), while NT-proBNP level only was associated with heart failure symptoms. We developed a score system consisted of biomarkers and clinical parameters. The area under the curve of the scoring system receiver operating characteristic curve is 0.838 to predict the degree of myocardial diffuse fibrosis. Conclusions: In conclusion, we found that galectin-3 and MMP-2 were significantly associated with global cardiac fibrosis in HFpEF patients. We also combined plasma biomarkers and clinical data to identify HFpEF patients with more severe cardiac fibrosis.

The relationship among cardiac structure, dietary salt and aldosterone in patients with primary aldosteronism.

Salt intake is highly associated with cardiac structure in patients with primary aldosteronism (PA). We investigated the association among dietary salt intake, aldosterone and left ventricular mass in patients with PA. We enrolled 158 patients with PA and 158 patients with essential hypertension. We measured 24-hour urinary sodium (UNa) and aldosterone (UAldo) level and echocardiography parameters. In patients with PA, the UAldo level was positively correlated with left ventricular mass index (LVMI; r=0.231, p=0.007). The UNa level was not linearly correlated with left ventricular structural parameters in patients with PA. To test if UNa has a non-linear relationship with LVMI among patients with PA, we categorized the participants according to the tertile of UNa (low, median, and high tertile). PA patients with medium tertile of UNa had significant lower LVMI than the other two groups (LVMI: 144.1 ± 42.9, 121.1 ± 33.4, and 136.7 ± 32.8 g/m2, from the lowest to the highest tertile of Una; analysis of variance p=0.006, post-hoc p <0.05). Multifactor analysis of variance confirmed this finding after adjustment for clinical parameters. Post-hoc analyses revealed that the high UNa tertile was associated with higher left ventricular end-diastolic volume compared with medium UNa tertile; while the low UNa tertile was associated with higher mean wall thickness compared with medium UNa tertile. The findings imply the reasons for increased LVMI may be different in patients with the highest and lowest UNa tertile. In conclusion, the medium tertile of 24-hour UNa is associated with lowest LVMI in patients with PA.

Evolutional change in epicardial fat and its correlation with myocardial diffuse fibrosis in heart failure patients.

OBJECTIVES: The aim of this study was to characterize the characteristics of epicardial fat (EAT) in different stage heart failure (HF) patients and its relationship between cardiac fibrosis. BACKGROUND: EAT is visceral adipose tissue that possesses inflammatory properties. Inflammation and obesity are associated with cardiac fibrosis, but the relationship between cardiac fibrosis and EAT is unknown. METHODS: EAT volume was measured using cardiac magnetic resonance imaging (CMR) in 180 subjects: 58 patients with systolic HF, 63 patients with HF and preserved ejection fraction, and 59 patients without HF. CMR derived myocardial extracellular volume (ECV) was used for fibrosis quantification. RESULTS: Patients with systolic HF had significantly more EAT compared with patients with HF and preserved ejection fraction or the control group (patients without HF) (indexed EAT volume [mL/m2], 27.0 [22.7-31.6] vs 25.6 [21.4-31.2] and 24.2 [21.0-27.6], P < .05). The adjusted EAT amount was associated with ECV completely independent of age, hypertension, diabetes, etiology of HF, left ventricular ejection fraction, CMR-late gadolinium enhancement (LGE), left ventricular mass index, and left ventricular end-diastolic volume index (correlation coefficient: 0.49; 95% confidence interval: 0.12-0.86, P < .01). Increased CMR ECV was more associated with EAT in those with advanced age, male sex, LGE on magnetic resonance imaging-LGE images, and less left ventricular end-diastolic volume index. CONCLUSIONS: EAT volume is highly associated with CMR ECV independent of traditional risk factors and left ventricular mass or volume. Whether EAT plays a role in the long-term prognosis of HF requires future investigation.

Clinical feasibility of Gd-EOB-DTPA-enhanced MR imaging for assessing liver function: validation with ICG tests and parenchymal cell volume.

OBJECTIVE: Using Gd-EOB-DTPA-enhanced MRI to assess liver function and validate with indocyanine green (ICG) tests and parenchymal cell volume (PCV). METHODS: Nineteen patients scheduled for operation were enrolled. Functional liver volume (FLV) was computed from 20min post-contrast images. ICG retention was measured in serum 15min after injection. The histological PCV was determined from resected liver specimen. RESULTS: FLV showed significantly correlated with ICG retention (ICG-R15: r=-0.47, P=.042) and PCV (r=0.814, P<.001). CONCLUSIONS: Gd-EOB-DTPA-enhanced MRI is clinically feasible for quantifying liver function.

Endocardial Remodeling in Heart Failure Patients with Impaired and Preserved Left Ventricular Systolic Function--A Magnetic Resonance Image Study.

Left ventricular (LV) trabeculation has been studied in certain forms of cardiomyopathy. However, the changes of LV endocardial trabeculation during the remodeling process leading to heart failure (HF) are unclear. Seventy-four patients with systolic heart failure (SHF), 65 with heart failure with preserved ejection fraction (HFpEF) and 61 without HF were prospectively enrolled. All subjects received magnetic resonance imaging (MRI) study including cine, T1 and late gadolinium enhancement (LGE) images. Trabecular-papillary muscle (TPM) mass, fractal dimension (FD) and extracellular volume (ECV) were derived. The results showed that TPM mass index was higher in patients with SHF than that in patients with HFpEF and non-HF. The TPM mass-LV mass ratio (TPMm/LVM) was higher in SHF group than that in HFpEF and non-HF. FD was not different among groups. The presence of LGE was inversely associated with TPM mass index and TPMm/LVM while the ECV were positively associated with TPMm/LVM. The FD was positively associated with LV chamber size. In conclusion, TPM increases in patients with SHF and are probably related to myocardial cell hypertrophy and fibrotic repair during remodeling. The FD increases with the dilatation of LV chamber but remain unchanged with the deterioration of LV function.

Pericardial fat is associated with ventricular tachyarrhythmia and mortality in patients with systolic heart failure.

OBJECTIVE: Pericardial fat (PF) has been hypothesized to exert local pathogenic effects on nearby cardiac structures above and beyond that of systemic adiposity which might be associated with the presence of arrhythmia or even worse outcomes. The aims of this study was to characterize the relationship between PF and the prognosis in patients with systolic heart failure (HF). METHODS: This is a retrospective cohort study of a cardiac magnetic resonance imaging (CMRI) database from 2004 to 2011. Fifty patients with systolic HF underwent CMRI examinations were included. We also enrolled twenty patients with HF as the control group. The cine imaging was analyzed to derive total PF volumes, left ventricular volumes and mass and left ventricular ejection fraction by using a previously validated technique. The outcomes, including ventricular tachycardia (VT), ventricular fibrillation (VF) and total mortality were obtained by reviewing medical records. RESULTS: After a median follow-up of 694 days, patients with VT/VF had significant larger indexed PF volumes than those without [36.3 (32.8-43.1) ml/m(2) vs. 24.1 (20.2-27.6) ml/m(2), p = 0.001]. The mortality group also had significant larger indexed PF volumes (PF/body surface area) than those without [31.3 (22.8-38.4) ml/m(2) vs. 23.9 (19.8-27.3) ml/m(2), p = 0.010]. Indexed PF volumes were associated with the development of VT/VF (Hazard ratio, 7.510; 95% C.I, 0.901-62.582, p = 0.062) and mortality (Hazard ratio, 3.998; 95% C.I, 1.077-14.845, p = 0.038) by Cox's regression analyses. CONCLUSION: PF is associated with the development of VT/VF and long-term overall mortality in patients with systolic HF.

MRI evaluation of the adaptive response of the contralateral kidney following nephrectomy in patients with renal cell carcinoma.

PURPOSE: To study the adaptive responses of the contralateral kidney and its association with renal outcome in patients with renal cell carcinoma (RCC) following radical nephrectomy (RN). MATERIALS AND METHODS: Eleven patients with RCC scheduled for RN and 15 control patients scheduled for adrenalectomy (Control) were prospectively recruited. All subjects underwent 4 MRI studies: 1 before surgery and 3 at 1 week, 1 month and 3 months after surgery, respectively. T2-weighted imaging and dynamic contrast-enhanced imaging were performed to estimate the renal volume and renal blood flow (RBF) of the contralateral kidney, respectively. The patients' serum creatinine levels were examined to determine the estimated glomerular filtration rate (e-GFR). The changes in renal volume at 3 months and both RBF and e-GFR during the serial follow-up were compared and associations between both of them were measured in both groups. RESULTS: In the RN group, RBF increased at 1 week (2.78 ± 0.93 mL/min/g, P = 0.002) and 1 month (2.65 ± 0.85 mL/min/g, P = 0.002), compared with presurgical values (1.94 ± 0.61 mL/min/g), and it returned to presurgical levels at 3 months (2.11 ± 0.73 mL/min/g, P = 0.432). In contrast, e-GFR decreased at 1 week (56.4 ± 20.3 mL/min/1.73 m(2) , P = 0.049) and 1 month (52.4 ± 18.8 mL/min/1.73 m(2) , P = 0.027), compared with presurgical values (66.3 ± 18.3 mL/min/1.73 m(2) ), and it returned to presurgical levels at 3 months (73.3 ± 29.5 mL/min/1.73 m(2) , P = 0.496). The renal volume increased at 3 months compared with baseline (198 ± 87 versus 329 ± 175 mL, P < 0.001). The change in renal volume was correlated with the change in RBF at 1 week (r = 0.609, P = 0.047). CONCLUSION: In patients with RCC following RN, an early increase in RBF of the contralateral kidney is associated with late renal hypertrophy which might normalize glomerular hyperfiltration and restore renal function.

CXCR4 Antagonist TG-0054 Mobilizes Mesenchymal Stem Cells, Attenuates Inflammation, and Preserves Cardiac Systolic Function in a Porcine Model of Myocardial Infarction.

Interaction between chemokine stromal cell-derived factor 1 and the CXC chemokine receptor 4 (CXCR4) governs the sequestration and mobilization of bone marrow stem cells. We investigated the therapeutic potential of TG-0054, a novel CXCR4 antagonist, in attenuating cardiac dysfunction after myocardial infarction (MI). In miniature pigs (minipigs), TG-0054 mobilized CD34(+)CXCR4(+), CD133(+)CXCR4(+), and CD271(+)CXCR4(+) cells into peripheral circulation. After isolation and expansion, TG-0054-mobilized CD271(+) cells were proved to be mesenchymal stem cells (designated CD271-MSCs) since they had trilineage differentiation potential, surface markers of MSCs, and immunosuppressive effects on allogeneic lymphocyte proliferation. MI was induced in 22 minipigs using balloon occlusion of the left anterior descending coronary artery, followed by intravenous injections of 2.85 mg/kg of TG-0054 or saline at 3 days and 7 days post-MI. Serial MRI analyses revealed that TG-0054 treatment prevented left ventricular (LV) dysfunction at 12 weeks after MI (change of LV ejection fraction from baseline, -1.0 ± 6.2% in the TG-0054 group versus -7.9 ± 5.8% in the controls). The preserved cardiac function was accompanied by a significant decrease in the myocardial expression of TNF-α, IL-1ß, and IL-6 at 7 days post-MI. Moreover, the plasma levels of TNF-α, IL-1ß, and IL-6 were persistently suppressed by the TG-0054 treatment. Infusion of TG-0054-mobilized CD271-MSCs reduced both myocardial and plasma cytokine levels in a pattern, which is temporally correlated with TG-0054 treatment. This study demonstrated that TG-0054 improves the impaired LV contractility following MI, at least in part, by mobilizing MSCs to attenuate the postinfarction inflammation. This insight may facilitate exploring novel stem cell-based therapy for treating post-MI heart failure.

CMR-verified diffuse myocardial fibrosis is associated with diastolic dysfunction in HFpEF.

OBJECTIVES: The purpose of this study was to investigate diffuse myocardial fibrosis in patients with systolic heart failure (SHF) and in patients with heart failure with preserved ejection fraction (HFpEF) and the association with diastolic dysfunction of the left ventricle (LV). BACKGROUND: Increased diffuse myocardial fibrosis may impair LV diastolic function. However, no study has verified the association between the degree of diffuse myocardial fibrosis and the severity of impaired diastolic function in SHF and HFpEF. METHODS: Forty patients with SHF, 62 patients with HFpEF, and 22 patients without HF underwent cardiac magnetic resonance (CMR), including T1 mapping and cine CMR on a 3-T system. Extracellular volume fraction (ECV), a measure of diffuse myocardial fibrosis, was quantified from T1 mapping. Systolic and diastolic functions of the LV were assessed by cine CMR. The ECV values and LV functional indexes were compared among the 3 groups. Associations between ECV and LV diastolic function were also investigated. RESULTS: Compared with patients without HF, significantly higher ECV was found in patients with SHF (31.2% [interquartile range (IQR): 29.0% to 34.1%] vs. 27.9% [IQR: 26.2% to 29.4%], p < 0.001) and HFpEF (28.9% [IQR: 27.8% to 31.3%] vs. 27.9% [IQR: 26.2% to 29.4%], p = 0.006). Peak filling rate, a diastolic functional index assessed by cine CMR, was significantly decreased in patients with SHF (1.00 s(-1) [IQR: 0.79 to 1.49 s(-1)] vs. 3.86 s(-1) [IQR: 3.34 to 4.48 s(-1)], p < 0.001) and HFpEF (2.89 s(-1) [IQR: 2.13 to 3.50 s(-1)] vs. 3.86 s(-1) [IQR: 3.34 to 4.48 s(-1)], p < 0.001). Myocardial ECV was significantly correlated with peak filling rate in the HFpEF group (r = -0.385, p = 0.002), but no correlation was found in the SHF and non-HF groups (r = 0.030, p = 0.856 and r = -0.238, p = 0.285, respectively). CONCLUSIONS: In patients with HF, only those with HFpEF show a significant correlation between increased diffuse myocardial fibrosis and impaired diastolic function. Diffuse myocardial fibrosis plays a unique role in the pathogenesis of HFpEF.

Conductive channels identified with contrast-enhanced MR imaging predict ventricular tachycardia in systolic heart failure.

OBJECTIVES: This study evaluated whether the conductive channel (CC) identified by late gadolinium enhanced-cardiac magnetic resonance (LGE-CMR) is associated with ventricular tachycardia (VT) in patients with systolic heart failure (HF). BACKGROUND: One recent study demonstrated that the CC formed by heterogeneous tissue within the core scar could be detected by LGE-CMR and that the CC is responsible for clinical VT. We hypothesized that the CC could help identify HF patients at risk for VT. METHODS: A total of 63 patients from a CMR database with left ventricular ejection fraction (LVEF) below 50% and with hyperenhancement on LGE-CMR were included. The cine and LGE images were analyzed to derive the LV function and scar characteristics, and to identify the CC. The outcomes, including VT, ventricular fibrillation (VF), and total mortality, were obtained by reviewing medical records. RESULTS: After a median 1,379 (interquartile range: 271 to 1,896) days of follow-up, 8 patients had VT/VF attacks and 14 patients died. Among the CMR-measured parameters, only the probability of identifying the CC by LGE-CMR was higher in patients with VT/VF than those without VT/VF (75.0% vs. 16.4%, p < 0.001). The probability of identifying the CC was also higher in the total mortality group than the survival group (50.0% vs. 16.3%, p = 0.004). The other LGE-CMR variables were not significantly different between the 2 groups. A univariate Cox regression model showed that CC identification was positively associated with VT/VF attacks (hazard ratio [HR]: 27.032, 95% confidence interval [CI]: 3.291 to 222.054, p = 0.002) and excess total mortality (HR: 4.766, 95% CI: 1.643 to 13.824, p = 0.004). The LVEF was inversely associated with VT/VF attacks (HR: 0.119, 95% CI: 0.015 to 0.977, p = 0.048) and excess total mortality (HR: 0.491, 95% CI: 0.261 to 0.925, p = 0.028) during follow-up. CONCLUSIONS: We demonstrated that CC identification using LGE-CMR can help identify HF patients at risk for VT/VF.

Contrast-enhanced MRI index of diffuse myocardial fibrosis is increased in primary aldosteronism.

PURPOSE: To assess the degree of myocardial fibrosis in patients with primary aldosteronism (PA). MATERIALS AND METHODS: Twenty-five patients with PA and 12 age-matched healthy volunteers underwent cine and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) on a 1.5 T MR system. From volume-time curves of cine MRI, the time for deceleration (Tdec) was determined to assess the left ventricle (LV) chamber stiffness. Based on phase-sensitive reconstructed LGE images, a fibrosis index called enhancement value (EV) was computed as the signal intensity change in the myocardium over blood before and after contrast. Both Tdec and EV were compared between patients and controls. The association between Tdec and EV was investigated. RESULTS: Patients showed a significantly higher EV (0.43 ± 0.05 vs. 0.36 ± 0.07; P = 0.002) and a significantly shorter Tdec (11.5 ± 3.5 %RR vs. 15.3 ± 2.4 %RR; P = 0.004) than controls. Significant correlations between EV and Tdec were observed in patients (r = -0.46, P = 0.018), in controls (r = -0.68, P = 0.015) and in all subjects (r = -0.63, P < 0.001). CONCLUSION: The fibrosis index is increased in patients with PA and the increase imposes an adverse effect on LV diastolic function.

Exercise training increases myocardial perfusion in residual viable myocardium within infarct zone.

PURPOSE: To study the effect of exercise training on the myocardial perfusion in the postinfarct myocardium. MATERIALS AND METHODS: Twenty-nine patients with stable chronic myocardial infarction were randomly assigned to either a training group (N = 17) or a control group (N = 12). The training group received a 3-month exercise program. Cardiovascular MR was first performed before the training to establish a baseline, and subsequently performed once again upon conclusion of the program. Late gadolinium enhancement was used both to define the infarct and remote zones and to quantify the ratio of the residual viable myocardium (VMR) within the infarct zone. The myocardium was divided into subendocardial and subepicardial layers with equal thickness. The interval change of myocardial perfusion reserve (MPR) was computed for each zone and layer. The association between the exercise-induced perfusion change and VMR was analyzed for layers of the infarct zone. RESULTS: In the training group, the remote zone showed significantly increased MPR. The infarct zone showed no perfusion change in the subendocardial layer, but it demonstrated significantly increased MPR in the subepicardial layer. In the infarct zone, the change in MPR was associated with VMR. CONCLUSION: In chronic myocardial infarction, the exercise-induced perfusion change in the infarct zone is proportional to the amount of residual viable myocardium.

Sequential changes of myocardial microstructure in patients postmyocardial infarction by diffusion-tensor cardiac MR: correlation with left ventricular structure and function.

BACKGROUND: We used diffusion-tensor cardiac MR to investigate myocardial microstructure changes, including tissue integrity (mean diffusivity [MD], fractional anisotropy) and fiber architecture (helix angles) in patients with recent myocardial infarction (MI). This study aimed to investigate the sequential changes of myocardial microstructure and its relationships with changes of macrostructure and function of the left ventricle post-MI. METHODS AND RESULTS: Seventeen patients (age, 55.1+/-11.5 years; all men) participated in the follow-up study. Diffusion-tensor cardiac MR, cine gradient echo for left ventricle function, and late gadolinium enhancement for viability were measured from recent to chronic MI (median interval, 191 days). When compared with the remote zone, the infarct-adjacent zone showed overall increase of MD (2-way MANOVA, F(1,16)=36.3; P<0.001), decrease of fractional anisotropy (F(1,16)=5.8; P=0.029), and decrease of mean helix angles (F(1,16)=62.0; P<0.001). From recent to chronic MI, there was overall sequential decrease of MD (F(1,16)=22.6; P<0.001) and increase of fractional anisotropy (F(1,16)=7.8; P=0.013). Multiple linear regression showed that the improvement of wall thickening in the infarct-adjacent zone correlated with sequential decrease of MD in the infarct-adjacent zone (r=-0.70; P=0.002) and increase of mean helix angles (ie, more right-handed helical myofiber reorientation, predominantly subendocardial location) in the remote zone (r=0.60; P=0.011). Likewise, wall thickening in the remote zone correlated with MD in the remote zone (r=-0.72; P=0.001) and mean helix angles in the infarct-adjacent zone (r=0.72; P=0.001). CONCLUSIONS: Diffusion-tensor cardiac MR suggests that sequential zonal improvement of tissue integrity and fiber architecture remodeling both associate with sequential recovery of zonal wall thickening of the left ventricle from recent to chronic MI.

Perfusion of residual viable myocardium in nontransmural infarct zone after intervention: MR quantitative myocardial blood flow measurement.

PURPOSE: To assess regional myocardial perfusion in patients with chronic myocardial infarction (MI) in relationship to the extent of residual viable myocardium. MATERIALS AND METHODS: The study was approved by the local ethics committee; written informed consent was obtained from each participant. Twenty-nine patients with first onset of MI who underwent successful primary percutaneous coronary intervention at least 6 months thereafter were studied. Delayed enhancement magnetic resonance (MR) imaging was performed to define the infarct zone and its viable myocardial ratio (VMR), quantified by the percentage of the nonscarred pixels relative to the total pixels in the infarct zone. First-pass contrast material-enhanced MR imaging was performed to estimate regional perfusion and myocardial perfusion reserve (MPR) in the infarct region. Paired comparisons in perfusion and MPR were tested with nonparametric Wilcoxon matched-pairs test. A difference with P < .05 was considered significant. Correlation was tested with Pearson analysis. RESULTS: The infarct region showed significant impairment of regional perfusion at rest (mean, 0.966 [mL x min(-1)]/g +/- 0.271 [standard deviation] vs 1.151 [mL x min(-1)]/g +/- 0.282; P = .024) and during stress (mean, 1.789 [mL x min(-1)]/g +/- 0.732 vs 2.753 [mL x min(-1)]/g +/- 0.806; P < .0001) and a reduced MPR (mean, 1.923 +/- 0.678 vs 2.486 +/- 0.836; P < .0001) as compared with remote myocardium. The estimated perfusion, with stress, of the residual viable myocardium was preserved (2.993 [mL x min(-1)]/g +/- 1.451 vs 2.753 [mL x min(-1)]/g +/- 0.806), and the difference was not significant. Furthermore, stress perfusion (R = 0.385; P = .039) and MPR (R = 0.434; P = .018) in the infarct zone were significantly correlated with VMR, suggesting that preservation of myocardial perfusion in the infarct region reflects the amount of viable myocardium. CONCLUSION: Reduced perfusion in the infarct zone is related to the extent of the viable myocardium.

First-pass myocardial perfusion cardiovascular magnetic resonance at 3 Tesla.

PURPOSE: To test the feasibility of first-pass contrast-enhanced myocardial perfusion imaging at 3 Tesla and to evaluate the change in perfusion index between normal, remote and ischemic myocardium, we obtained perfusion index from healthy subjects and patients with coronary artery stenosis. MATERIALS AND METHODS: First-pass contrast-enhanced perfusion imaging was performed on 12 patients and 32 age-matched healthy subjects in both rest and dipyridamole-induced stress states. After bolus injection of contrast agent, Gd-DTPA with dose of 0.025 mmol/kg body weight and injection time of 1.5 s, three short-axis images from apex to base of the left ventricle (LV) were acquired for 80 cardiac cycles using saturation recovery turbo FLASH sequence. The maximal upslope (Upslope) was derived from the signal-time curves of the LV cavity and myocardium to measure myocardial perfusion. Within 72 hours after cardiovascular magnetic resonance examination, patients received coronary angiography, and the results were correlated with cardiovascular magnetic resonance results. RESULTS: Using our protocol of contrast agent administration, sufficient perfusion contrast was obtained without susceptibility-induced signal drop-out at the interface between LV cavity and the myocardium. In healthy volunteers, Upslope showed no dependence on myocardial segments or coronary territories. Upslope increased significantly from rest to stress in normal myocardium (0.09 +/- 0.03 vs. 0.16 +/- 0.05, p < 0.001) and remote myocardium (0.09 +/- 0.03 vs. 0.13 +/- 0.03, p < 0.001), whereas in ischemic myocardium the change was insignificant (0.11 +/- 0.03 vs. 0.10 +/- 0.04, p = ns). This resulted in significant difference in the ratio of Upslope at stress to that at rest, representing myocardial perfusion reserve, between ischemic and non-ischemic myocardium (0.96 +/- 0.41 vs. 1.71 +/- 0.42, p < 0.001 for ischemic vs. normal myocardium; 0.96 +/- 0.41 vs. 1.59 +/- 0.40, p < 0.001 for ischemic vs. remote myocardium). CONCLUSIONS: First-pass gadolinium-enhanced myocardial perfusion imaging at 3 Tesla is feasible. The Upslope ratio can differentiate ischemic from non-ischemic myocardium.

Diffusion tensor magnetic resonance imaging mapping the fiber architecture remodeling in human myocardium after infarction: correlation with viability and wall motion.

BACKGROUND: Diffusion tensor magnetic resonance imaging (DT-MRI) provides a means for nondestructive characterization of myocardial architecture. We used DT-MRI to investigate changes in direction-dependent water diffusivity to reflect alterations in tissue integrity (trace apparent diffusion coefficients [ADCs] and fractional anisotropy [FA]), as well as indicators of remodeling of fiber helix angles, in patients after myocardial infarction. METHODS AND RESULTS: Thirty-seven patients (35 men, 2 women; median age, 59) after acute myocardial infarction (median interval from onset, 26 days) were enrolled. DT-MRI was performed at the midventricular level to measure trace ADC, FA, and helix angles of myofibers. Helix angles were grouped into left-handed helical fibers, circumferential fibers, and right-handed helical fibers. Measurements were correlated with viability and regional wall motion assessed by contrast-delay-enhancement and cine MRI, respectively. The infarct zone showed significantly increased trace ADC and decreased FA than the remote zone. The percentage of left-handed helical fibers increased from the remote zone (mean +/- SD, 13.3 +/- 5.8%) to the adjacent zone (19.2 +/- 9.7%) and infarct zone (25.8 +/- 18.4%) (MANOVA, P = 0.004). The percentage of right-handed helical fibers decreased from the remote zone (35.0 +/- 9.0%) to the adjacent zone (25.5 +/- 11.5%) and infarct zone (15.9 +/- 9.2%) (P < 0.001). Multiple linear regression showed that the percentage of left-handed helical fibers of the infarct zone was the strongest correlate of infarct size and predictor of ejection fraction. CONCLUSIONS: In vivo DT-MRI of postinfarct myocardium revealed a significant increase in trace ADC and a decrease in FA, indicating altered tissue integrity. The redistribution of fiber architecture correlated with infarct size and left ventricular function. This technique may help us understand structural correlates of functional remodeling after infarction.