T1 Characteristics in Different Disease Stages of Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and is frequently associated with microvascular dysfunction and myocardial fibrosis, even in early disease stages. Cardiovascular magnetic resonance (CMR) enables tissue characterization through T1 mapping, where T1 values reflect the myocardial content of water, protein, and lipids and are notably influenced by fibrosis [1]. Recent studies have proposed that stress T1 and the difference between stress and rest T1 (ΔT1) may serve as potential markers of (micro)vascular dysfunction [2]. The aim of this study was to assess native rest T1, stress T1, and ΔT1 across different disease stages of HCM.

Methods: Four groups were studied: patients with overt HCM (maximum wall thickness [MWT] >15 mm), mild HCM (MWT 12–15 mm), genotype-positive carriers without hypertrophy (MWT < 12 mm), and genotype-negative healthy controls. All three HCM groups carried a class 4 or 5 pathogenic variant in MYH7 or MYBPC3. CMR with native and (adenosine-induced) stress T1 mapping was performed in all participants on a 3T MR scanner. Two short-axis slices (basal-mid and mid-apical) were acquired, each divided into six segments according to the American Heart Association (AHA) segmentation model, yielding a total of 12 myocardial segments per subject (Figure 1a). Analysis was performed using CVI42 software with a 10% offset. ΔT1 was calculated by subtracting rest T1 from stress T1.

Results: 37 participants were included (10 overt HCM, 10 mild hypertrophy, 12 carriers and 5 healthy controls), the baseline characteristics and average global rest T1, stress T1 values, and ΔT1 values are provided in Table 1. T1 increased significantly during stress in each group during stress. Global rest T1, stress T1 values, and ΔT1 values did not significantly differ between groups (Table1).
Segmental analysis showed that HCM patients had a significantly lower ΔT1 in segment 9 compared to controls and carriers (44.6±18.3 vs. 68.5±18.1 and 68.6±27.5 ms; p=0.033 and p=0.029, respectively) (Figure 1d). Notably, segment 9 often corresponded to the location of MWT. Carriers exhibited significantly higher rest T1 values in segment 7 and 8 than controls (1254.8±35.8 ms vs. 1195.2±47.9 ms, p=0.012, and 1279.5±38.1 ms vs. 1228.4±44.3 ms, p=0.029) (Figure 1b).

Conclusion: These preliminary results demonstrate that global rest T1, stress T1 and ΔT1 values do not differ between groups. On a segmental level, significant differences were evident, particularly in regions corresponding to myocardial hypertrophy. Increased segmental T1 is observed even in carriers, suggesting early alterations occurring before the onset of hypertrophy. Future studies in larger cohorts are needed to validate these observations and to explore correlations between T1 metrics, perfusion imaging, and fibrosis assessment using late gadolinium enhancement.

Table 1: Baseline characteristics of each patient group.

	G+/Ph+ (n=10)	G+/mild hypertrophy (n=10)	G+/Ph- (n=12)	G- controls (n=5)
Age (years)	53.3 ± 11.6	52.0 ± 10.3	44.9 ± 13.0	52.6 ± 16.4
BMI (kg)	27.2 ± 2.5	26.9 ± 4.1	23.4 ± 3.8	24.4 ± 2.9
% male	80	70	25	60
Left ventricular end-diastolic diameter (mm)	48.5 ± 4.6	46.0 ± 4.2	43.9 ± 9.2	47.8 ± 5.3
Left ventricular end-diastolic volume (mL)	156.1 ± 46.0	165.0 ± 29.4	149.8 ± 49.5	139.8 ± 34.9
Left ventricular end-systolic volume (mL)	66.5 ± 24.4	59.0 ± 18.3	53.7 ± 20.3	57.0 ± 17.6
Stroke volume (mL)	109.3 ± 15.1	106.0 ± 14.2	96.1 ± 30.8	82.8 ± 17.9
Ejection fraction (%)	64.8 ± 5.7	64.7 ± 5.6	64.3 ± 3.4	59.8 ± 3.3
Maximum wall thickness (mm)	19.3 ± 3.4	13.2 ± 0.9	8.6 ± 1.3	9.5 ± 0.6
LV mass (g)	152.4 ± 28.4	112.7 ± 20.1	87.6 ± 29.7	82.8 ± 16.4
Rest T1 (ms)	1253.8 ± 53.3	1229.9 ± 40.5	1252.5 ± 24.0	1231.4 ± 42.0
Stress T1 (ms)	1309.9 ± 47.2	1294.7 ± 40.7	1320.4 ± 30.6	1296.8 ± 27.7
ΔT1 (ms)	56.1 ± 31.1	64.8 ± 15.9	67.9 ± 26.1	65.4 ± 19.9

All values are mean ± SD or %. Figure 1: a) AHA segment distribution (basal and mid segments) b) distribution of segmental rest T1 values c) distribution of segmental stress T1 values, and d) distribution of segmental ΔT1 values. 1 = healthy controls, 2 = carriers, 3 = mild hypertrophy patients, 4 = HCM patients (values are in ms). *p≤0.05 for carriers vs. healthy controls, **p≤0.05 for HCM patients vs. carriers and healthy controls.