In hypertrophic cardiomyopathy (HC), there are significant variations in left ventricular (LV) wall thickness and fibrosis, which necessitates a volumetric coverage. Slice-interleaved T 1 (STONE) mapping sequence allows for the assessment of native T 1 time with complete coverage of LV myocardium. The aims of this study were to evaluate spatial heterogeneity of native T 1 time in patients with HC. Twenty-nine patients with HC (55 ± 16 years) and 15 healthy adult control subjects (46 ± 19 years) were studied. Native T 1 mapping was performed using STONE sequence which enables acquisition of 5 slices in the short-axis plane within a 90 seconds free-breathing scan. We measured LV native T 1 time and maximum LV wall thickness in each 16 segments from 3 slices (basal, midventricular and apical slice). Late gadolinium enhanced (LGE) magnetic resonance imaging was acquired to assess the presence of myocardial enhancement. In patients with HC, LV native T 1 time was significantly elevated compared with healthy controls, regardless of the presence or absence of LGE (mean native T 1 time; LGE positive segments from HC, 1,141 ± 46 ms; LGE negative segments from HC, 1,114 ± 56 ms; segments from healthy controls, 1,065 ± 35 ms, p <0.001). Elevation of native T 1 time was defined as >1,135 ms, which was +2SD of native T 1 time by STONE sequence in healthy controls. A total of 120 of 405 (30%) LGE negative segments from patients with HC showed elevated native T 1 time. Prevalence of segments with elevated native T 1 time for basal, midventricular, and apical slice was 29%, 25%, 38%, respectively. Significant correlation was found between LV wall thickness and LV native T 1 time (y = 0.029 × −22.6, p <0.001 by Spearman’s correlation coefficient). In conclusion, substantial number of segments without LGE showed elevation of native T 1 time, and whole-heart T 1 mapping revealed heterogeneity of myocardial native T 1 time in patients with HC.
Hypertrophic cardiomyopathy (HC) is a genetic heart disease, characterized by unexplained left ventricular (LV) hypertrophy, myofibrillar disarray, and myocardial fibrosis. HC is regarded as the most common nontraumatic cause of sudden death in young generation. Postmortem studies revealed that fibrosis is either present as focal fibrosis or diffuse fibrosis by intercellular deposition of collagen fibers. In vivo, focal fibrosis can be assessed noninvasively with late gadolinium enhanced (LGE) magnetic resonance imaging (MRI). Several studies showed that the presence of myocardial enhancement on LGE MRI is associated with worse clinical outcome in HC. However, LGE MRI can delineate only focal myocardial fibrosis not diffuse interstitial fibrosis. Therefore, noninvasive assessment of diffuse interstitial fibrosis is of interest in terms of better risk stratification in patients with HC. Myocardial T 1 mapping emerged as a noninvasive method to quantify diffuse myocardial abnormality. Extracellular volume calculated by pre- and post-T 1 mapping can detect diffuse myocardial abnormality in patients with diastolic heart failure, diabetic cardiomyopathy, and cardiac amyloidosis. Recent studies showed that native (noncontrast) T 1 mapping can differentiate myocardial abnormality of HC from healthy myocardium. However, in this study, myocardial T 1 time was calculated by one point sampling of midseptal wall. To date, no data are available regarding native T 1 time heterogeneity based on the 16-segment model. The aims of this study were to compare native T 1 time between patients with HC and healthy controls and to evaluate spatial heterogeneity of native T 1 time in patients with HC using slice-interleaved T 1 (STONE) mapping.
Methods
Twenty-nine HC (56 ± 16 years; 22 men) and 15 healthy adult control subjects (46 ± 19 years; 9 men) free of any cardiovascular diseases were studied. Phenotypes of HC were septal hypertrophy (n = 25) and apical hypertrophy (n = 4). In our cohort, there were 6 patients with HC with LV outflow obstruction. Healthy controls had no history of hypertension, dyslipidemia, diabetes mellitus, and smoking. All participants were in sinus rhythm at the time of scan. The study protocol was approved by our institutional review board. Written informed consent was obtained from all subjects. Using a 1.5-T MR scanner and 32-channel cardiac coil (Achieva; Philips Healthcare, Best, the Netherlands), cine MRI, LGE MRI, and native T 1 mapping images of LV were acquired. Electrocardiogram monitoring leads were positioned with the subject in the supine position. Vertical and horizontal LV long-axis cine images were acquired using a steady-state free precession sequence. LV volumes and mass were calculated from an LV short-axis stack of cine images extending from the apex to the base (repetition time, 3.3 ms; echo time, 1.6 ms; flip angle, 60°; field-of-view, 320 × 320 mm; acquisition matrix, 128 × 128; slice thickness, 8 mm; and gap, 2 mm). Native T 1 mapping was acquired using a STONE sequence which enables acquisition of 5 slices in the short-axis plane within a 90 seconds free-breathing scan (repetition time, 2.8 ms; echo time, 1.4 ms; flip angle, 70°; field-of-view, 360 × 351 mm; voxel size, 2.1 × 2.1 mm; slice thickness, 8 mm; turbo field echo factor, 86; and sensitivity encoding factor, 2). Fifteen minutes after the injection of 0.2 mmol/kg gadobenate dimeglumine, LGE images were acquired using a 3-dimensional sequence with following parameters: repetition time, 5.3 ms; echo time, 2.1 ms; flip angle, 70°; field-of-view, 320 × 320 × 125 mm 3 ; acquisition matrix, 224 × 224 × 23; spatial resolution, 1.4 × 1.4 × 1.5 mm; reconstruction resolution, 0.6 × 0.6 × 0.8 mm. Cine MRI was analyzed using a commercial workstation (Extend MR WorkSpace, version 2.3.6.3; Philips Healthcare). To determine LV mass, epicardial and endocardial LV borders were manually traced on the short-axis images. LV mass was calculated as the sum of the myocardial volume multiplied by the specific gravity (1.05 g/mL) of myocardial tissue. Visual assessment was performed to assess the presence or absence of myocardial enhancement on LGE images using the 16-segment model. Myocardial segments from patients with HC were allocated into 2 group base on the presence or absence of hyperenhancement on LGE MRI. Short-axis slices of native T 1 mapping images were analyzed using a custom software (MedIACare, Boston, Massachusetts). For calculating LV native T 1 time, the 3 short-axis LV slices were divided into 6 segments for basal and midventricular slices, 4 segments for apical slice using the anterior right ventricular-LV insertion point as reference. Motion correction was performed using the adaptive registration of varying contrast-weighted images for improved tissue characterization approach. The 16-segment model was used to assess native T 1 time in each segment. To evaluate interobserver reproducibility, measurements of LV native T 1 time from 10 patients with HC were independently taken by 2 observers. One of the 2 observers measured LV native T 1 time twice to assess intraobserver reproducibility. Data were analyzed using SPSS software (version 17.0; SPSS, Inc., Chicago, Illinois) and MedCalc for Windows (version 14.8.1; MedCalc Software, Ostend, Belgium). Continuous values are presented as mean ± SD. Categorical values are expressed as number (%). For continuous variables, normality was evaluated by the Shapiro–Wilk test. Significance of difference was evaluated using the unpaired t test for normal distributed variables and Mann–Whitney U test for skewed variables. The chi-square test was used to assess the difference for categorical variables. Significance of difference of native T 1 time between 4 groups was evaluated by one-way analysis of variance with Tukey’s post hoc test. Relation between LV native T 1 time and LV wall thickness was calculated by Spearman’s correlation coefficient. To evaluate reproducibility of native T 1 time measurement, intraclass correlation coefficient (ICC) and repeatability coefficient were evaluated. Repeatability coefficients were calculated as 1.96 times the SD of the differences on the Bland–Altman plots. A 2-sided p value <0.05 was considered statistically significant.
Results
Table 1 summarizes the characteristics of study subjects. Patients with HC were heavier than healthy controls. Table 2 summarizes cardiac MR findings. LV mass index was significantly higher in patients with HC than in control subjects. LGE hyperenhancement of LV myocardium was observed in 13 of 29 patients with HC (45%). Figure 1 showed representative native T 1 mapping images from a patient with HC with asymmetric septal hypertrophy and a healthy control. Mean native T 1 time over the 16 segments was elevated to 1,175 ms in this patient with HC. However, no myocardial enhancement was observed on LGE images. Figure 2 demonstrated segment-based comparison of native T 1 time between HC and healthy controls. We excluded 6 segments due to severe artifacts on T 1 mapping images from analysis. Comparing to segments from healthy controls (n = 240), mean native T 1 time was significantly elevated in patients with HC (1,117 ± 55 vs 1,065 ± 35 ms, p <0.001). Furthermore, mean native T 1 time of LGE negative segments from HC was significantly higher than from healthy controls (1,114 ± 56 vs 1065 ± 35 ms, p <0.001). LGE positive segments from HC showed highest native T 1 time (1,141 ± 46 ms). Figure 3 demonstrated the location of segments with elevated native T 1 time in patients with HC. Elevation of native T 1 time was defined as >1,135 ms, which was +2SD of native T 1 time by STONE sequence in healthy controls. A total of 120 of 405 (30%) LGE negative segments showed elevated native T 1 time. Prevalence of segments with elevated native T 1 time for basal, midventricular and apical slice was 29%, 25%, 38%, respectively. Figure 4 illustrated myocardial native T 1 time across all myocardial segments in both HC and healthy controls. Substantial regional heterogeneity was found in myocardial native T 1 time in patients with HC. Comparing to healthy controls, native T 1 time was significantly elevated in patients with HC in 15 of 16 myocardial segments except for basal inferolateral wall. Figure 5 showed relation between native T 1 time and LV wall thickness in end diastole. Significant positive correlation was found between native T 1 time and LV wall thickness (y = 0.029 × −22.6, p <0.001). Reproducibility of native T 1 time measurement was high, with ICC of 0.91 (95% CI 0.88 to 0.93) and repeatability coefficient of 46 ms (4.1% of mean native T 1 time) for intraobserver reproducibility, ICC of 0.86 (95% CI 0.86 to 0.92) and repeatability coefficient of 51 ms (4.5% of mean native T 1 time) for interobserver reproducibility.
| Hypertrophic Cardiomyopathy (N = 29) | Healthy Controls (N = 15) | P-Value ∗ | |
|---|---|---|---|
| Demographics | |||
| Male | 22 (76%) | 9 (60%) | 0.27 |
| Age (years) | 56 ± 16 | 46 ± 19 | 0.091 |
| Height (cm) | 173 ± 9 | 173 ± 9 | 0.98 |
| Body weight (kg) | 88 ± 14 | 78 ± 14 | 0.028 |
| Body mass index (kg/m 2 ) | 29.3 ± 5 | 26 ± 4 | 0.012 |
| Body surface area, (m 2 ) | 2.05 ± 0.19 | 1.92 ± 0.21 | 0.045 |
| Systolic blood pressure (mmHg) | 122 ± 17 | 122 ± 11 | 0.93 |
| Diastolic blood pressure (mmHg) | 71 ± 16 | 71 ± 10 | 0.90 |
| Heart rate (beats per minute) | 65 ± 10 | 70 ± 10 | 0.15 |
| New York Heart Association functional classification | |||
| Class I | 20 (69%) | – | – |
| Class II | 9 (31%) | – | – |
| Class III or IV | 0 (0%) | – | – |
∗ p Value represents significance of difference between hypertrophic cardiomyopathy patients and healthy controls.
| Hypertrophic Cardiomyopathy (N = 29) | Healthy Controls (N = 15) | P-Value ∗ | |
|---|---|---|---|
| End diastolic volume index (mL/m 2 ) | 75 ± 16 | 80 ± 12 | 0.33 |
| End systolic volume index (mL/m 2 ) | 27 ± 10 | 31 ± 7 | 0.11 |
| Stroke volume index (mL/m 2 ) | 48 ± 9 | 48 ± 7 | 0.89 |
| Left ventricular ejection fraction (%) | 65 ± 8 | 61 ± 5 | 0.051 |
| Left ventricular mass index (g/m 2 ) | 74 ± 22 | 47 ± 12 | <0.001 |
| Heart rate (beats per minute) | 65 ± 10 | 70 ± 10 | 0.15 |
| Late gadolinium enhancement positive subjects | 13 (45%) | 0 (0%) | 0.003 |
∗ p Value represents significance of difference between hypertrophic cardiomyopathy patients and healthy controls.
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