Correlation between right ventricular T1 mapping and right ventricular dysfunction in non-ischemic cardiomyopathy

The purpose of this study was to investigate a noninvasive method for quantifying diffuse myocardial fibrosis with cardiac magnetic resonance imaging (CMRI). Diffuse myocardial fibrosis is a fundamental process in pathologic remodeling in cardiomyopathy and is postulated to cause increased cardiac stiffness and poor clinical outcomes. Although regional fibrosis is easily imaged with cardiac magnetic resonance, there is currently no noninvasive method for quantifying diffuse myocardial fibrosis. We performed CMRI on 45 subjects (25 patients with heart failure, 20 control patients), on a clinical 1.5-T CMRI scanner. A prototype T(1) mapping sequence was used to calculate the post-contrast myocardial T(1) time as an index of diffuse fibrosis; regional fibrosis was identified by delayed contrast enhancement. Regional and global systolic function was assessed by cine CMRI in standard short- and long-axis planes, with echocardiography used to evaluate diastology. An additional 9 subjects underwent CMRI and endomyocardial biopsy for histologic correlation. Post-contrast myocardial T(1) times correlated histologically with fibrosis (R = -0.7, p = 0.03) and were shorter in heart failure subjects than controls (383 +/- 17 ms vs. 564 +/- 23 ms, p < 0.0001). The T(1) time of heart failure myocardium was shorter than that in controls even when excluding areas of regional fibrosis (429 +/- 22 ms vs. 564 +/- 23 ms, p < 0.0001). The post-contrast myocardial T(1) time shortened as diastolic function worsened (562 +/- 24 ms in normal diastolic function vs. 423 +/- 33 ms in impaired diastolic function vs. 368 +/- 20 ms in restrictive function, p < 0.001). Contrast-enhanced CMRI T(1) mapping identifies changes in myocardial T(1) times in heart failure, which appear to reflect diffuse fibrosis.

The relationship between arrhythmogenic right ventricular cardiomyopathy (ARVC) and pure fat replacement of the right ventricle is unclear. Myocardial thickness, epicardial fat thickness, percent fibrosis, and intramyocardial fat infiltration were measured in 16 sections each from 25 hearts with typical (fibrofatty) ARVC, 7 hearts with fat replacement of the right ventricle without fibrosis (FaRV), and 18 control hearts from patients who died of noncardiac causes. Patients with fibrofatty ARVC were younger than those with FaRV (31+/-14 versus 44+/-13 years, P=.02), more likely to have a history of arrhythmias or a family history of premature sudden death (56% versus 0%, P=.01), more likely male (80% versus 29%, P=.02), and less likely to have coexisting conditions that might have predisposed to sudden death (12% versus 86%, P<.001). Fibrofatty ARVC was characterized by right ventricular myocardial thinning, fat infiltration of the anterobasal and posterolateral apical right ventricle, subepicardial left ventricular fibrofatty replacements (64%), myocyte atrophy (96%), and lymphocytic myocarditis (80%). FaRV showed normal or increased myocardial thickness, a diffuse increase in intramyocardial and epicardial fat, little inflammation, and an absence of myocardial atrophy. Intramyocardial fat was frequently seen in normal hearts, especially in the anteroapical region, but was less extensive than in fibrofatty ARVC and FaRV. ARVC is a familial arrhythmogenic disease characterized by fibrofatty replacement of myocytes with scattered foci of inflammation. Fat infiltration per se is probably a different process that should not be considered synonymous with ARVC.

Metabolic and vascular disturbances contribute to diabetic cardiomyopathy, but the role of interstitial fibrosis in early disease is unproven. We sought to assess the relationship between imaging markers of diffuse fibrosis and myocardial dysfunction and to link this to possible causes of early diabetic cardiomyopathy. Hemodynamic and metabolic data were measured in 67 subjects with type 2 diabetes mellitus (age 60±10 years) with no cardiac symptoms. Myocardial function was evaluated with standard echocardiography and myocardial deformation; ischemia was excluded by exercise echocardiography. Calibrated integrated backscatter was calculated from parasternal long-axis views. T1 mapping was performed after contrast with a modified Look-Locker technique using saturation recovery images. Amino-terminal propeptides of procollagens type I and III, as well as the carboxy-terminal propeptide of procollagen type I, were assayed to determine collagen turnover. Subjects with abnormal early diastolic tissue velocity (E(m)) had shorter postcontrast T1 values (P=0.042) and higher calibrated integrated backscatter (P=0.007). They were heavier (P=0.003) and had worse exercise capacity (P<0.001), lower insulin sensitivity (P=0.003), and blunted systolic tissue velocity (P=0.05). Postcontrast T1 was associated with diastolic dysfunction (E(m) r=0.28, P=0.020; E/E(m) r=-0.24, P=0.049), impaired exercise capacity (r=0.30, P=0.016), central adiposity (r=-0.26, P=0.046), blood pressure (systolic r=-0.30, P=0.012; diastolic r=-0.49, P<0.001), and insulin sensitivity (r=0.30, P=0.037). The association of T1 with E/E(m) (β=-0.31, P=0.017) was independent of blood pressure and metabolic disturbance. Amino-terminal propeptide of procollagens type III was linked to diastolic dysfunction (E(m) r=-0.32, P=0.008) and calibrated integrated backscatter (r=0.30, P=0.015) but not T1 values. The association between myocardial diastolic dysfunction, postcontrast T1 values, and metabolic disturbance supports that diffuse myocardial fibrosis is an underlying contributor to early diabetic cardiomyopathy.