Myocardial late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy caused by mutations in troponin I

Abstract

Objective: To examine the influence of genotype on late gadolinium enhancement (LGE) and the potential of cardiovascular magnetic resonance (CMR) to detect preclinical hypertrophic cardiomyopathy.

Design: Prospective, blinded cohort study of myocardial LGE in a genetically homogeneous population.

Patients: 30 patients with disease causing mutations in the recognised hypertrophic cardiomyopathy gene for cardiac troponin I (TNNI3): 15 with echocardiographically determined left ventricular hypertrophy (LVH+) and 15 without (LVH-).

Main outcome measures: CMR measures of regional left ventricular function, wall thickness, and mass, and the extent and distribution of LGE.

Results: LGE was found in 12 (80%) LVH+ patients but with variable extent (mean 15%, range 3-48%). LGE was also found in two (13%) LVH- patients but the extent was limited (3.6%) and both patients were found to have an abnormal ECG and regional hypertrophy by cine CMR. The extent of LGE was positively associated with clinical markers of sudden death risk (21% with > or = 2 risk factors v 7% with < or = 1 risk factor, p = 0.02) and left ventricular mass (r = 0.56, p < 0.001) and was inversely associated with ejection fraction (r = -0.58, p < 0.001). Segmental analysis showed that as regional wall thickness increased, LGE was more prevalent (p < 0.0001) and more extensive (r = 0.98, p = 0.001).

Conclusion: In patients with disease causing mutations in TNNI3, focal fibrosis was not detected by LGE CMR before LVH and ECG abnormalities were present. Once LVH is present, LGE is common and the extent correlates with adverse clinical parameters. This suggests that focal fibrosis is closely linked to disease development.

Figure 1

Progression of late gadolinium enhancement (LGE) in a family with more than four gene positive members: H805 (Arg145Trp), a family with late onset, low risk disease without progression during follow up and little LGE. abn, abnormal; CMR, cardiovascular magnetic resonance; EF, ejection fraction; n, normal.

Figure 2

Progression of LGE in a family with more than four gene positive members. H15 (Arg162Gln), a family with early onset disease (in males) with rapid phenotype development, significant enhancement in the hypertrophied regions, and significant risk of sudden death.

Figure 3

Progression of LGE in a family with more than four gene positive members. H136 (Arg186Gln), a family with disease that progressed from normal through hypertrophy to heart failure. There is significant LGE in hypertrophied myocardium and massive LGE in the patient with previous left ventricular hypertrophy > 30 mm and subsequent wall thinning.

Figure 4

Combining the 480 myocardial segments from the 30 patients, the (A) prevalence and (B) extent of LGE increases with increasing segmental wall thickness.