To assess left ventricular remodeling patterns using cardiac computed tomography (CT) in children with congenital heart disease and correlate these patterns with their clinical course.
Left ventricular volume and myocardial mass were quantified in 17 children with congenital heart disease who underwent initial and follow-up end-systolic cardiac CT studies with a mean follow-up duration of 8.4 ± 9.7 months. Based on changes in the indexed left ventricular myocardial mass (LVMi) and left ventricular mass-volume ratio (LVMVR), left ventricular remodeling between the two serial cardiac CT examinations was categorized into one of four patterns: pattern 1, increased LVMi and increased LVMVR; pattern 2, decreased LVMi and decreased LVMVR; pattern 3, increased LVMi and decreased LVMVR; and pattern 4, decreased LVMi and increased LVMVR. Left ventricular remodeling patterns were correlated with unfavorable clinical courses.
Baseline LVMi and LVMVR were 65.1 ± 37.9 g/m2 and 4.0 ± 3.2 g/mL, respectively. LVMi increased in 10 patients and decreased in seven patients. LVMVR increased in seven patients and decreased in 10 patients. Pattern 1 was observed in seven patients, pattern 2 in seven, and pattern 3 in three patients. Unfavorable events were observed in 29% (2/7) of patients with pattern 1 and 67% (2/3) of patients with pattern 3, but no such events occurred in pattern 2 during the follow-up period (4.4 ± 2.7 years).
Left ventricular remodeling patterns can be characterized using cardiac CT in children with congenital heart disease and may be used to predict their clinical course.
Left ventricular hypertrophy (LVH) is a critical factor predicting adverse cardiovascular events such as arrhythmia, heart failure, and sudden cardiac death (
This retrospective study was approved by the local Institutional Review Board and the requirement for informed consent was waived.
Between June 2011 and August 2016, 17 patients with congenital heart disease (median age at the first cardiac CT, 22 days; range, 2 days to 16 years; male:female = 10:7) underwent initial and follow-up electrocardiography (ECG)-synchronized end-systolic cardiac CT examinations (time interval, 8.4 ± 9.7 months) using a second-generation dual-source scanner (SOMATOM Definition Flash; Siemens Healthineers, Forchheim, Germany). Therefore, 34 cardiac CT examinations were included in this study. Demographic characteristics, diagnosis, and treatment of the study population are described in
The fundamental scan parameters of the cardiac CT were as follows: 2 × 64 × 0.6-mm slices with the z-flying focal spot technique; gantry rotation time, 0.28 seconds; temporal resolution, 75 ms; slice width, 0.75 mm; and reconstruction interval, 0.4 mm. Scan protocols were further optimized to minimize radiation dose and maintain diagnostic image quality (
Iodinated contrast agent (Iomeron 400, iomeprol 400 mg I/mL; Bracco Imaging SpA, Milan, Italy; 1.5–2.0 mL/kg) was administered intravenously using a dual-head power injector at an injection rate of 0.3–3.0 mL/s. A tri-phasic or quadri-phasic injection protocol was utilized to achieve uniform cardiovascular enhancement and minimal peri-venous streak artifacts from undiluted contrast agent. The scan delay time was determined using a bolus tracking technique with a trigger threshold of 150 HU in the left ventricular cavity.
Volume CT dose index and dose-length product values based on a 32-cm phantom were 3.5 ± 4.7 mGy and 60.6 ± 98.8 mGy·cm, respectively. The effective dose value of cardiac CT calculated by multiplying the dose-length product by the age, sex, and tube voltage-specific conversion factors was 1.2 ± 1.4 mSv (
Left ventricular end-systolic cavity volume and myocardial mass were quantified by using a commercially available workstation (Advantage Workstation 4.6; GE Healthcare, Milwaukee, WI, USA). First, the epicardial border of the left ventricle was delineated consecutively using one-click identification of the left ventricle, a 3D region-growing method, and manual adjustment. The mitral and aortic valve planes were then defined manually. For the total volume of the left ventricle, the left ventricular cavity volume was separated from the left ventricular myocardial volume by using 3D threshold-based segmentation. The left ventricular myocardial mass (in grams) was calculated by multiplying the specific gravity of the myocardium (1.05 g/mL or g/cm3) by the quantified myocardial volume. Left ventricular mass-volume ratio (LVMVR) was calculated by dividing the left ventricular myocardial mass by the left ventricular volume. The left ventricular volume and myocardial mass were indexed to body surface area. Based on a previous article using the same segmentation method, the indexed left ventricular myocardial mass (LVMi) was categorized as either no hypertrophy (< 60.2 g/m2), borderline hypertrophy (60.2–74.0 g/m2), or definite hypertrophy (≥ 74.1 g/m2) (
Left ventricular overloaded conditions in each patient were characterized based on the following echocardiographic and cardiac CT findings: pressure overload was regarded present when substantial obstruction was observed in the aortic arch (pressure gradient ≥ 20 mm Hg), aortic valve (≥ 36 mm Hg), or left ventricular outflow tract (≥ 30 mm Hg), or when the aortic valve annulus was small (Z score < −2). Volume overload was considered present when aortic or mitral regurgitation greater than grade 2 (or moderate) was observed, or when right-to-left or bidirectional shunt flow through a ventricular septal defect was identified.
Based on changes in LVMi and LVMVR between the two serial cardiac CT examinations, LVR was categorized into one of four patterns: pattern 1, increased LVMi and increased LVMVR (
All patients were followed up (4.4 ± 2.7 years) to determine whether an unfavorable event had occurred, such as re-operation or re-intervention for a residual lesion causing left ventricular pressure or volume overload, application of extracorporeal membrane oxygenation, left ventricular dysfunction, myocardial infarction, arrhythmia, heart failure, or cardiac death.
Continuous variables are presented as mean ± standard deviation or median with range, and categorical variables are expressed as frequency with percentage. To explore their clinical significance, LVR patterns were correlated with unfavorable clinical courses. Descriptive data analyses were performed using Excel (Microsoft Corp., Redmond, WA, USA).
The mean baseline LVMi and LVMVR in 17 patients were 65.1 ± 37.9 g/m2 and 4.0 ± 3.2 g/mL, respectively. Of 34 examinations, LVMi showed no hypertrophy in 20, borderline hypertrophy in eight, and definite hypertrophy in six. There was no change in the degree of LVH between serial examinations in 14 patients, but 3 patients showed a change in category. LVMi increased from 52.2 ± 39.0 g/m2 at the initial CT to 70.4 ± 33.1 g/m2 at the follow-up CT in 10 patients during the interval of 0.9 ± 1.0 years, whereas LVMi decreased from 77.9 ± 42.8 g/m2 at the initial CT to 63.1 ± 40.5 g/m2 at the follow-up CT in 7 patients during the interval of 0.5 ± 0.4 years. On the other hand, LVMVR increased from 2.1 ± 1.1 g/mL at the initial CT to 3.4 ± 1.1 g/mL at the follow-up CT in 7 patients during the interval of 0.9 ± 1.1 years, while LVMVR decreased from 6.6 ± 4.4 g/mL at the initial CT to 3.0 ± 2.6 g/mL at the follow-up CT in 10 patients during the interval of 0.6 ± 0.4 years.
Of 17 patients, pressure overload was present in 11 patients (aortic arch obstruction in six, a small aortic valve annulus in three, left ventricular outflow obstruction in two, aortic valve stenosis in one, and pulmonary artery banding in one), and two kinds of pressure overload were identified in two patients. Of 17 patients, volume overload was present in four patients (mitral regurgitation in two, aortic regurgitation in one, and shunt through a ventricular septal defect in one). Two patients had a combination of pressure and volume overload.
Patterns of LVR are summarized in
This study demonstrated that LVR patterns could be characterized using cardiac CT in children with congenital heart disease, and the patterns were used to predict clinical course. Based on the preliminary results of this study, the most favorable clinical course was observed in pattern 2 (decreased LVMi and LVMVR), the most unfavorable clinical course in pattern 3 (increased LVMi and decreased LVMVR), and the clinical course in pattern 1 (increased LVMi and LVMVR) was intermediate between the two extremes.
LVH is an adaptive reaction to pressure overloaded conditions that increase left ventricular wall stress to maintain cardiac performance despite the elevated left ventricular systolic pressure, but is associated with excess cardiac mortality and morbidity (
Favorable LVR occurs as a regression process after the relief of overloaded conditions. In a previous study using cardiac MRI (
As previously mentioned, LVH may develop as a compensatory remodeling process (
Maladaptive LVR may produce patterns 3 or 4. Pattern 3 is characterized by a disproportionally greater increase in ventricular volume than that in myocardial mass, resulting in a reduction in LVMVR. In contrast, pattern 4 is characterized by a disproportionally greater decrease in ventricular volume than that in myocardial mass, leading to increased LVMVR. In this study, a poor clinical outcome frequently occurred in pattern 3. Pattern 4 was observed in patients with aortic regurgitation after aortic valve replacement (
The same strategy as that used in this study may be applied to characterize right ventricular remodeling patterns in response to severe pulmonary regurgitation in patients with repaired tetralogy of Fallot and other congenital heart diseases, mainly involving the right ventricle (
Retrospective study design and the small study population are major limitations of this study. Its retrospective nature might lead to selection bias in which more severe cases were enrolled in the study population. Moreover, statistical and subgroup analyses were limited due to the small number of patients with variable patient age and pathology. The time intervals between serial cardiac CT examinations were also highly variable. Pathology-based verification of left ventricular mass quantification using 3D CT data is practically impossible. Nonetheless, the same 3D threshold-based approach as used in this study previously demonstrated high reproducibility with a mean difference between the two evaluation sessions of 2.3 ± 1.1% (
In conclusion, LVR patterns can be characterized using cardiac CT in children with congenital heart disease and may be used to predict their clinical course.
Four-chamber views of initial
Four-chamber views of initial
Four-chamber views
Case Number | Sex | Age at 1st Cardiac CT | Time Interval between Serial CT Examinations | Diagnosis and Previous Treatment | Interval Treatment |
---|---|---|---|---|---|
1 | M | 2 days | 19 days | TGA, VSD, S/P BAS | Arterial switch operation |
2 | M | 2 days | 82 days | HLHS variant, CoA | Bilateral PAB |
3 | F | 4 days | 895 days | CoA | Arch repair |
4 | M | 6 days | 378 days | CoA | Arch repair |
5 | M | 7 days | 361 days | CoA | Arch repair |
6 | M | 15 days | 357 days | IAA, VSD, S/P arch repair | N/A |
7 | F | 16 days | 349 days | CoA | Arch repair |
8 | F | 20 days | 436 days | Critical aortic stenosis, S/P Sano modified Norwood operation | Pulmonary artery angioplasty, right modified Blalock-Taussig shunt |
9 | F | 22 days | 77 days | IAA, VSD, S/P arch repair | N/A |
10 | M | 1 month | 344 days | CoA | Arch repair |
11 | M | 8 months | 98 days | Congenially-corrected TGA with intact ventricular septum, S/P PAB | N/A |
12 | M | 8 months | 161 days | Large ASD, BPD, pulmonary hypertension | Sutureless repair, ASD closure |
13 | F | 17 months | 99 days | Williams syndrome | Modified sliding aortoplasty |
14 | M | 9 years | 82 days | Williams syndrome | Aortoplasty, bypass graft |
15 | F | 10 years | 31 days | TGA, VSD, tricuspid atresia, S/P Fontan operation | VSD extension, mitral valvuloplasty |
16 | F | 10 years | 929 days | CoA | N/A |
17 | M | 16 years | 19 days | Bicuspid aortic valve, aortic regurgitation | Bentall operation |
ASD = atrial septal defect, BAS = balloon atrial septostomy, BPD = bronchopulmonary dysplasia, CoA = coarctation of aorta, CT = computed tomography, F = female, HLHS = hypoplastic left heart syndrome, IAA = interrupted aortic arch, M = male, N/A = not applicable, PAB = pulmonary artery banding, S/P = status post, TGA = transposition of great arteries, VSD = ventricular septal defect
Left Ventricular Remodeling Patterns | LVMi | LVMVR | No. of Cases | Pressure Overload | Volume Overload | Unfavorable Events | Follow-Up Period (Years) |
---|---|---|---|---|---|---|---|
Pattern 1 | Increased | Increased | 7 | 57% (4/7) | 29% (2/7) | 29% (2/7) | 2.5–8.2 |
Pattern 2 | Decreased | Decreased | 7 | 57% (4/7) | 14% (1/7) | 0% (0/5) | 1.1–8.2 |
Pattern 3 | Increased | Decreased | 3 | 100% (3/3) | 33% (1/3) | 67% (2/3) | 0.8–8.3 |
LVMi = indexed left ventricular myocardial mass, LVMVR = left ventricular mass-volume ratio