Pediatric cardiomyopathies caused by different causes either ischemic or non-ischemic and primary (genetic) or secondary (non-genetic). They have diagnostic challenge to clinicians, so it is important to detect the underlying cause as it then leads to improvement of outcome with disease-specific treatment [5].
As reported by Cox et al. [6], the patient population of pediatric cardiomyopathies was divided into 4 types: dilated (53.8%), hypertrophic (34.2%), restrictive (3.2%), and other or mixed (8.9%). And these findings are in approximation with result of our study in which DCM represents 43.1% and was the most common form followed by hypertrophic (25%) and restrictive (2.3%).
Nineteen out of 44 (43.1%) cases were dilated cardiomyopathy. These patients were retrospectively assessed and most of these cases have an idiopathic form (42%) and this agrees with the study conducted by Hong [6], who reported that in pediatric population most cases have idiopathic forms of disease and maybe, in the future, these cases will be found to have genetic or familial causes with subsequent changes in the epidemiology of disease [7].
However, Latus et al. [8] reported that majority of the cases in pediatric population have idiopathic form, the most common known causes are myocarditis (46%) and this with our study results in which among studied dilated cases, we found that myocarditis is the commonest cause of dilation found in seven patients (41%) (Fig. 3).
In our study, the cardiac MRI was highly effective in the assessment of ventricular volumes with increased indexed EDV of the left ventricle, reduced EF and global hypokinesia in all cases (100%) of DCM. The left ventricular wall thinning presents only in advanced cases. One of the cases has associated dilated right ventricle. All our previous results in DCM are in agreement with all previous study in literatures by Iacucci et al. [7] and Lehrke et al. [9].
Eleven out of 42 cases (26.2%) in our study, patients were diagnosed as hypertrophic cardiomyopathy (HCM) and represent the second common type in our study, this finding is a close match with a previous study reported by Hong [6] as mentioned before.
In all our cases, diagnosis based on both echo and MRI findings with mean thickness were 13 mm. Ten out of 11 cases showing asymmetric focal left ventricular hypertrophy and only one case with apical form. These findings are in close match with a previous study conducted by Rickers et al. [10], they reported that asymmetric involvement of the inter-ventricular septum is the most common form of the disease, accounting for an estimated 60% to 70% of the cases of HCM and this is in approximation of our finding (90%) in our HCM cases, and these relatively high percentage in our study may be due to our small sample size.
Also, Rickers et al. [10] reported that hypertrophy in this phenotype is typically most evident in the antro-septal myocardium and this is a close match with our study in which asymmetric hypertrophy adjacent to the left ventricular outflow tract including the anterior and infero-septal walls present in more than two thirds (91%) of our patients. However, areas of relative sparing of hypertrophy are also commonly visualized in HCM patients but this finding is not noted in our study.
Systolic anterior motion (SAM) effect is found in 6 out of 10 cases (60%) of focal sigmoid-shaped hypertrophy and this matched with the study that records the presence of SAM in 31–61% of HCM in his study and it is associated with resting LVOTO in 25–50% of cases (based on several series studies) [11,12,13]. And this matched with our finding in which the turbulent jet through the left ventricular outflow track coupled with an eccentric jet of mitral regurgitation, that was highly suggestive of a significant LVOT obstruction which was noted in 7 of our cases (63.6%) (Fig. 4).
Three out of these cases with LVOT obstruction showed papillary muscle abnormalities in the form of accessory papillary muscle, bifid muscle with abnormal insertion in to mitral valve leaflet and all three cases showing LVOT obstruction, and these findings are with a previous reported study by Maron and Maron [14] that found resting or provo cable LVOT obstruction in up to 70% of HCM cases and relates it to complex anatomical relationships between the basal septum, LVOT, mitral valve, and papillary muscles (Fig. 4).
Three out of our 11 HCM cases (27.2%) had family history of HCM. And this is a close match with the study conducted by Maron et al. [15] that found eleven (27.5%) of his patients had a family history of HCM at the time of his study. We assessed two cases (sisters to already diagnosed one of study cases) without HCM diagnosis or any clinical suspicion as trial for MRI screening, and LV crypt was seen in two cases together with mild focal asymmetrical hypertrophy in antero-septal segment.
However, we only represent only two cases but this matched with other previously mentioned results by Moon and McKenna [16] that documented screening of the family members of a patient with HCM is important because the first-degree relatives of such a patient have a 50% chance of being a gene carrier; he found a high rate of occurrence of 81% (13 of 16 subjects) in cine MR imaging in HCM mutation carriers who had not yet developed LV hypertrophy. And this may be a point for further research study as a non-invasive technique for screening.
We have diagnosed LVNC in only five cases out of referral eight cases (previously diagnosed by echo) (62.5%). We depend on MRI diagnostic criteria published by a study conducted by Mikolich et al. [17] in which they found 15 of 22 patients (68%) had a diagnosis of LVH on their 2-D echo study, while only 3 had LVH on their cardiac MRI study. Based on these data, patients with LVH on 2-D echo should be considered for a cardiac MRI examination to determine if the increased LV wall thicknesses are truly LVH or an undiagnosed LV non-compaction.
Zuccarino et al. [18] reported that the apical and mid ventricular segments of both the inferior and lateral walls are the most common affected segments in LVNC cases and this with our study results in which all cases had shown region of non-compaction along the lateral wall and sparing septal wall (Fig. 5).
Three of our patient have associated other congenital heart disease, one case has hypoplastic left heart syndrome while another one has PDA and the other ASD and this matches with study conducted by Ichida [19] who described this as a non-isolated form. The remaining two cases have an isolated form and this was different from the study conducted by Zuccarino et al. [18] who reported that the isolated form is the commonest form.
The incidence of ARVD in our study was (4.7%); however, the true incidence of ARVD is unknown and is categorized as a rare disease with estimated prevalence at 1:5000 [2]. We have two cases with ARVD diagnosis. One of them showed a normal-size right ventricle with reduced ejection fraction (30%), regional hypokinesia and dyskinesia with small aneurysmal dilation near RVOT, and no detected fatty infiltration in the right or left ventricle; also, this case demonstrated right atrial dilation secondary to tricuspid regurge; there was subtle patchy enhancement in RVOT. The other case shows fatty infiltration was detected in RVOT with dilated RV and RA with tricuspid regurgitation; however, no detected WMA (Fig. 6).
In a study carried out by Grosse-Wortmann et al. [20], they found that MRI is a useful tool in the diagnostic work-up of ARVC in children and adolescents in contrast to adult due to more subtle degree of WMA in this age group which are not detected by echocardiography but found on MRI. Also, in the pediatric age group, fibrofatty degeneration is found rarely and never without wall motion abnormalities, and this matches with the finding in our two cases.
As regards restrictive cardiomyopathy type, in our study, we have six referral patients with diastolic dysfunction; one of them has restrictive cardiomyopathy and the other five cases are diagnosed as constrictive pericarditis based on clinical, echo, and MRI findings. Although both restrictive cardiomyopathy and constrictive pericarditis are characterized by diastolic dysfunction and impairment of ventricular filling, they have different management and differentiation between them is very important.
In restrictive case, there were small both ventricles with significant decrease in EDV and ESV; however, there were normal EF of both ventricle and marked dilation of both atria associated with dilated IVC and hepatic veins while no pericardial thickening or effusion or pericardial enhancement (Fig. 7).
While in the other five cases that were diagnosed as constrictive pericarditis, there were also small both ventricles with significant decrease in EDV and ESV and normal EF of both ventricle; however, the main differentiating points were thickened pericardium with no enhancement in chronic cases and enhancement in acute setting and evidence of septal bounce that is more evident with respiration, flattening of the inter-ventricular septum with inspiration, and septum bounces to the right side with expiration.
In all studied referral cases, both morphological and functional parameter of restrictive cardiomyopathy and constrictive cardiomyopathy are similar apart from septal bounce which is diagnostic for constrictive pericarditis and detected on MRI using a real-time imaging sequence in the short-axis plan and thickened enhancing or non-enhancing pericardium and this point is superior assessed by MRI than echo. Our findings are a closer match with study conducted by Rammos et al. [21] that use the respiratory-related ventricular coupling to differentiate patients with constrictive pericarditis and RCM. However, the cases of constrictive pericarditis were excluded from our study and this is the only differentiating point.
Another form of restrictive cardiomyopathy type is the infiltrative form which also enters under secondary causes as previously mentioned in review. In our study, we have six cases; two of them with metabolic storage disease and were presented with diffuse hypertrophy as differential diagnosis to HCM cases while the remaining four cases were cardiomyopathy secondary to iron overload in thalassemia patients.
We add T2*-weighted image in our protocol in examination of patient with thalassemia and we found that myocardial iron deposition was found on gradient-echo images, with lower signal at higher echo time (TE) values and this matched with study conducted by Cozma [22]. He reported that myocardial T2* was shown to be a more reliable indicator of true myocardial iron content as compared to serum ferritin levels or liver iron. Myocardial T2* < 20 ms is significant iron deposition and < 10 ms is advanced iron deposition (Fig. 8).
In our study, we found that there was an agreement between echocardiography and cardiac MRI examination in evaluation of LVEF as demonstrated by Bland-Altman plot test Fig. 2. Among our 44 patients, the mean EF by echo was 54.4 + 19.7 SD and by cardiac magnetic resonance was 47.2 + 21.6 with a mean difference of 7.3%. SD of bias was 9.7 and the 95% limits of agreement were − 26.4 to 11.6. Our result are quite different from study conducted by Hoffmann et al. [23]. All of them found that mean differences between EF by cardiac magnetic resonance and echocardiography images were below 5%; however, we found that mean difference was 7%.
In our study, there was an overestimation of LVEF by echocardiography compared to CMR with a mean difference of about 7% between the two imaging modalities. As well, our results agreed with Rasha et al. [24] who observed agreement between echocardiography and CMR for estimation of LVEF in 37 patients with left ventricular dysfunction due to ischemic heart disease; the mean EF by CMR and echocardiography was 33.3% and 29% respectively with a mean difference of 4.3%. SD of bias was 6.73 and the 95% limit of agreement was − 8.90 to 7.5m and our result were mean EF by echo was 54.4 and by cardiac magnetic resonance was 47.2 with a mean difference of 7.3%. SD of bias was 9.7 and the 95% limits of agreement were − 26.4 to 11.6 with higher values in our study.
We have relatively high percentage of bias in comparison to all previous reported study, as all these studies were in adults and our study was in children, and need for further agreement that MRI is more accurate than echo in functional cardiac assessment due to relatively different anatomy between adult and children and challenge of echo technique in children.
As regards the delayed contrast enhancement finding in our study, LGE is found in 15 cases out of 31 cases (48.4%); however, the remaining 13 cases have no contrast study due to medical problems, the parent refusing or escape of contrast out of cannula. The enhancing cases were 7 DCM, 4 HCM, 1 ARVD,1 infiltrative cardiomyopathy, and two ischemic cases. The following regional patterns are presented in Table 4: mid-wall (n = 9), sub-endocardial extending to epicardial surface (transmural) (n = 4) (Fig. 3), and sub-epicardial (n = 2), sub-endocardial only (n = 2).
We found that there was correlation between the presence of LGE and MRI LVEF and LV volumes. The LVEF was lower and LV volume indices included (LVEDV, LVESV) were higher in patients with LGE compared with those without LGE with a statistically significant difference (p value = 0.001, p value = 0.003, and p value = 0.005, respectively).
Also, a major adverse effect found in 14 of our cases with higher incidence in enhancement cases (80%) as compared to non-enhancement ones (20%) with a statistically significant difference (p value ≤0.001). So as regards the correlation between enhancement and other variables, we found that adverse cardiac prognosis is associated with the presence of LGE.
These results agree with adult study carried out by Wu et al. [25] that correlates the presence and extent of CMR LGE with a higher risk of adverse cardiac outcomes in patients with non-ischemic cardiomyopathy (NICM) and LVEF 35% and LVEF trended lower and LV volume indexes were higher in those patients with LGE compared with those without LGE. And in correlation with the study also carried out by Assomull et al. [26].
Although we found a significantly higher incidence of adverse cardiac outcomes in NICM patients with positive LGE, the absence of LGE did not exclude the occurrence of adverse effect and we found an adverse effect in two patient (12.5%) without enhancement and this is in agreement with study carried out by Wu et al. (25) that found adverse cardiac effect in three patients of her study cases (9%) without LGE and they explained that not all adverse cardiac effect are caused by fibrosis, but may occur due to other causes such as by bundle branch or inter fasicular re-entry in arrhythmia and others.
From previous results LGE image can be used as clinical tool for suspecting cases with bad clinical out come and aid in management of these cases.
