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Introduction: Inflammation contributes to pathogenic ventricular remodeling. Recently, T1 mapping has been used to non-invasively measure interstitial myocardial fibrosis. We examined the association between baseline markers of systemic inflammation and interstitial fibrosis measured using T1 mapping at 10 years follow-up in MESA. Methods and Results: 1,156 participants underwent cardiac magnetic resonance imaging with T1 mapping. All analyses were stratified by gender. Three hierarchical multivariable linear regression models were constructed to assess the risk-adjusted association of baseline C-reactive protein (CRP), interleukin 6 (IL-6) and fibrinogen with 25 minutes post-contrast myocardial T1 time (T1Myo25). Shorter T1Myo25 reflect increasing levels of interstitial fibrosis. We found a non-linear relationship between IL-6 and T1Myo25 in males (Figure 1A). A significant negative association between T1Myo25 and increasing levels of IL-6 was found in males that reversed at IL-6 levels ≥2.7pg/ml. Moreover in males, increasing levels of fibrinogen were significantly negatively associated with T1Myo25, while a similar but non-significant trend was found for CRP (Figure 1B). In women, there was a similar inverse association between T1Myo25 and increasing levels of all three markers of systemic inflammation prior to adjusting for body mass index that became statistically non-significant following adjustment (Figure 1B). Similar associations with markers of inflammation were found using extracellular volume fraction and T1Myo12 as measures of interstitial fibrosis. Conclusions: Markers of systemic inflammation in males, particularly IL-6 and fibrinogen, are independently associated with increased interstitial fibrosis. In females, this association may be mediated by the obesity-induced inflammatory-state. These findings highlight the early role of inflammation in the pathogenesis of heart failure.

Background: Persons with diabetes mellitus (DM) have altered cardiac structure and function, which increases heart failure (HF) risk. Myocardial contraction fraction (MCF) is an echocardiographic global measure of fractional shortening recently applied to cardiac MRI. We sought to determine if MCF differed by DM status and if MCF predicts HF in the Multi-Ethnic Study of Atherosclerosis, a cohort which enrolled ethnically diverse adults aged 45-84 who were free of clinical CVD. Methods: Analyses included 4991 with MRI data for whom DM status could be ascertained. Left ventricle (LV) volumes and mass (LVM) were calculated by the summation of disks method from cine short axis images. Ejection fraction (EF) is defined as LV stroke volume (SV) / end diastolic luminal volume. MCF is defined as LV SV/ end diastolic myocardial volume. DM was defined as using hypoglycemic drugs or a fasting glucose>125mg/dl. Linear regression was utilized for cross sectional analyses of the association between MCF and DM status, adjusting for age, gender, race/ethnicity, BMI, systolic BP, BP drugs, and smoking. Cox proportional hazards modeling was used to compare MCF, EF and LV mass quartiles as predictors of HF, adjusting for the above variables and DM. Results: At baseline the mean age was 61.5 (SD 10), 52% were female, 39% white, and 61% minorities; 13% had impaired fasting glucose (IFG) and 12% DM. The table indicates LV measurements. After adjustment, DM status remained associated with a lower MCF (IFG -0.02, 95% CI -0.03,-0.01; DM -0.032, 95%CI -0.04, -0.02). There were 96 incident HF events. Compared to the 4 th quartile, the 1 st MCF quartile was associated with HF (adjusted HR 2.2; 95%CI 1.13, 4.43) as was 1 st EF quartile (adjusted HR 2.9; 95%CI 1.6, 5.2) and 4 th quartile LVM (adjusted HR 5.4; 95%CI 2.2, 13.2). Among those with DM, 39% were in the 1 st MCF quartile, compared to 27% in the 1 st EF and 33% in the 4 th LVM quartile. Conclusions: Incident HF is predicted by MCF. MCF may be a more sensitive marker for diabetic cardiomyopathy than EF or LVM. Ventricular Measures by Diabetes Status Glucose Category Parameter Normal 100-125 mg/dl Diabetes p-value MCF 0.66 (0.14) 0.61 (0.14) 0.59 (0.14) <0.001 EF, % 69 (7) 69 (8) 68 (9) 0.11 SV (ml) 87 (20) 86 (19) 86 (19) 0.05 LMV (g) 142 (38) 153 (41) 157 (43) <0.001 Mean (Std Dev)