Heterogeneity of intramural function in hypertrophic cardiomyopathy: mechanistic insights from MRI late gadolinium enhancement and high-resolution displacement encoding with stimulated echoes strain maps

Abstract

Background: In hypertrophic cardiomyopathy (HCM), myocardial abnormalities are commonly heterogeneous. Two patterns of late gadolinium enhancement (LGE) have been reported: a bright "confluent" and an intermediate intensity abnormality termed "diffuse," each representing different degrees of myocardial scarring. We used MRI to study the relation between intramural cardiac function and the extent of fibrosis in HCM. The aim of this study was to determine whether excess collagen or myocardial scarring, as determined by LGE MRI, are the primary mechanisms leading to heterogeneous regional contractile function in patients with HCM.

Methods and results: Intramural left ventricular strain, transmural left ventricular function, and regions of myocardial fibrosis/scarring were imaged in 22 patients with HCM, using displacement encoding with stimulated echoes (DENSE), cine MRI, and LGE. DENSE systolic strain maps were qualitatively and quantitatively compared with LGE images. Intramural systolic strain by DENSE was significantly depressed within areas of confluent and diffuse LGE but also in the core of the most hypertrophic nonenhanced segment (all P < 0.001 versus nonhypertrophied segments). DENSE demonstrated an unexpected inner rim of largely preserved contractile function and a noncontracting outer wall within hypertrophic segments in 91% of patients.

Conclusions: LGE predicted some but not all of the heterogeneity of intramural contractile abnormalities. This indicates that myocardial scarring or excess interstitial collagen deposition does not fully explain the observed contractile heterogeneity in HCM. Thus, myofibril disarray or other nonfibrotic processes affect systolic function in a large number of patients with HCM.

Figure 1

Patient with confluent late gadolinium enhancement in the inferior septum which colocalizes with a severe focal abnormality in radial DENSE (see Results for details).

Figure 2

The diffuse pattern of late gadolinium enhancement seen in the anterior septum matches the contractile abnormality seen with DENSE (see Results for details).

Figure 3

Patient where the systolic strain deficit extends well beyond the two clearly defined confluent lesions on the late gadolinium enhanced images (see Results for details).

Figure 4

Patient with extensive systolic intramural strain abnormality despite minimal late gadolinium gadolinium enhancement (see Results for details).

Figure 5

Abnormal systolic strain is seen not only in areas of confluent and diffuse late gadolinium enhancement but also in the most hypertrophic non-enhanced segment. Intramural function is reduced irrespective of type or presence of late gadolinium enhancement pattern in hypertrophic segments indicating that myocardial scarring and interstitial fibrosis cannot predict the entire spectrum of functional abnormalities.

Figure 6

Signal intensities in late gadolinium enhancement images varied depending on presence and type of late gadolinium enhancement. Confluent and diffuse patterns had significantly higher signal intensity than normal myocardium. The signal intensity in the most hypertrophic non-enhancing segment was not significantly different from that of normal myocardium.

Figure 7

Left panel 7A: Irrespective of segmental end-diastolic thickness, the myocardium exhibits on average more than 3 mm absolute systolic change in wall thickness. Note that excluding the most hypertrophic segments, absolute systolic change in wall thickness is on average more than 6 mm. In normal subjects, >3 mm represents normal absolute systolic change in wall thickness. Right panel 7B: With increasing end-diastolic thickness the myocardium exhibits reduced percent systolic wall thickening, which is a measure of transmural systolic strain. This seems paradoxical given that these patients have preserved ejection fractions and fairly extensive left ventricular hypertrophy. (Sample size per category was <6:572, 6–12:1272, 12–15:327, 15–20:449, 20–25:306, >25:134)

Figure 7

Left panel 7A: Irrespective of segmental end-diastolic thickness, the myocardium exhibits on average more than 3 mm absolute systolic change in wall thickness. Note that excluding the most hypertrophic segments, absolute systolic change in wall thickness is on average more than 6 mm. In normal subjects, >3 mm represents normal absolute systolic change in wall thickness. Right panel 7B: With increasing end-diastolic thickness the myocardium exhibits reduced percent systolic wall thickening, which is a measure of transmural systolic strain. This seems paradoxical given that these patients have preserved ejection fractions and fairly extensive left ventricular hypertrophy. (Sample size per category was <6:572, 6–12:1272, 12–15:327, 15–20:449, 20–25:306, >25:134)

Figure 8

Gadolinium delayed enhancement does not fully explain the observed functional abnormalities. For segments with end-diastolic wall thickness (EDWTh) < 12mm percent wall thickening was inversely proportional to the extent of delayed enhancement. However, for segments with EDWTh ≥ 12mm, transmural percent wall thickening was depressed irrespective of the extent of gadolinium delayed enhancement.