Exploiting Differences in Myocardial Compartments With Native T1 and Extracellular Volume Fraction for the Diagnosis of Hypertrophic Cardiomyopathy

Abstract

. At present, establishing native T1 reference ranges is needed for each particular scanner and software version because small variations in T1-mapping methodology can exert significant influence on normal reference ranges. 6 Native T1 decreases with some diseases (fat infiltration and iron overload) and increases in others (fibrosis, edema, and amyloid). In myocardial fibrosis, the native T1 elevation is likely from the interstitial compartment rather than cardiomyocyte compartment, but not definitively known.In contradistinction to native T1, ECV detects diseases limited to the interstitium (including myocardial vasculature). ECV exploits the extracellular nature of gadolinium contrast agents. The concentration of contrast in myocardium relative to the concentration in plasma (not whole blood) is a direct measure of the interstitial space after equilibration, as long as contrast agents are not protein-bound. The relative concentrations are derived from the change in relaxivity (ie, 1/T1) for myocardium and whole blood before and after contrast administration and then multiplying the resultant partition coefficient by (1 -hematocrit). The latter term accounts for the displacement of plasma by erythrocytes and enables computation of plasma contrast concentration from the whole-blood measurement from regions of interest measured from the T1 images.ECV and T1 have their respective limitations. The signal to noise ratio of the biological signal to be detected may be massive in some diseases (iron, Fabry, and amyloid) but smaller in diffuse fibrosis. Small signals are intrinsically harder to detect and more prone to potential biases and difficulties with quality control, particularly between centers. There is some evidence that measurement errors are lower at 1.5T than 3T and lower for ECV compared with native T1. 8 Because the ECV and the partition coefficient are ratios, some systematic T1 biases may cancel. However, ECV requires precise T1 measurement over a broader range of values and relies on a second measurement system for the hematocrit (Coulter counter), another potential source of error. ECV also varies slightly with contrast concentration possibly from water exchange effects in and out of cells. Therefore, variations in gadolinium contrast concentration (which relates to choice of contrast timing and dose) can yield slight differences in ECV values, for example, if double-dose or single-dose contrast is used or if time intervals between contrast bolus and post contrast T1 measures vary significantly.9 Both T1 and ECV can be prone to partial volume error from adjacent tissues (eg, blood) and off resonance, so care must be taken in their measurement.What might occur in myocardial compartments with HCM, particularly early HCM? The authors demonstrate early native T1 changes. This finding, in part, agrees with previous HCM studies, one measuring circulating peripheral biomarkers of fibrosis (presumably myocardial), 10 and another indicating elevations in myocardial ECV associated with increased pro-brain natr...

Isosorbide Dinitrate, With or Without Hydralazine, Does Not Reduce Wave Reflections, Left Ventricular Hypertrophy, or Myocardial Fibrosis in Patients With Heart Failure With Preserved Ejection Fraction

“…49 Native T1 signals, however, arise from the entirety of the myocardium, and thus reflect both the intracellular as well as the interstitial spaces. 50 The increased native T1 time, in the absence of a change in ECV, may thus be a reflection of changes occurring at the intracellular level (cardiomyocytes, cardiac fibroblasts, smooth muscle cells, and endothelial cells), including increased edema or cardiomyocyte disarray. 50,51 Finally, treatment with ISDN, with or without hydralazine, was poorly tolerated in this population and led to frequent adverse events.…”

“…50 The increased native T1 time, in the absence of a change in ECV, may thus be a reflection of changes occurring at the intracellular level (cardiomyocytes, cardiac fibroblasts, smooth muscle cells, and endothelial cells), including increased edema or cardiomyocyte disarray. 50,51 Finally, treatment with ISDN, with or without hydralazine, was poorly tolerated in this population and led to frequent adverse events. Overall, our findings are consistent with those of NEAT-HFpEF (Nitrate's Effect on Activity Tolerance in Heart Failure with Preserved Ejection Fraction) trial, which showed that isosorbide mononitrate decreased physical activity on accelerometry and led to numerically greater adverse events as compared with PB.…”

“…First, ECV calculations reflect interstitial changes, given its reliance on gadolinium, an extracellular contrast agent . Native T1 signals, however, arise from the entirety of the myocardium, and thus reflect both the intracellular as well as the interstitial spaces . The increased native T1 time, in the absence of a change in ECV, may thus be a reflection of changes occurring at the intracellular level (cardiomyocytes, cardiac fibroblasts, smooth muscle cells, and endothelial cells), including increased edema or cardiomyocyte disarray …”

Incremental Values of T1 Mapping in the Prediction of Sudden Cardiac Death Risk in Hypertrophic Cardiomyopathy: A Comparison With Two Guidelines

“…Alternatively, native T1 mapping is a robust biomarker indicating the pathologic hypertrophic remodeling in HCM ( 38 , 39 ). The myocardial tissue remodeling including cardiomyocyte disarray is also a risk factor for malignant arrhythmia ( 15 , 32 , 40 ). Furthermore, native T1 mapping is important for the detection of focal and diffuse fibrosis without the administration of contrast ( 14 ).…”

“…However, it is often confusing to define diffuse interstitial expansion by LGE ( 14 ). The amount of LGE also differs based on the chosen thresholding techniques ( 15 ).…”