Ventricular non-compaction in children: clinical characteristics and course☆

Abstract

Isolated left ventricular non-compaction (LVNC) is a rare cardiomyopathy characterized by prominent trabeculations and deep intratrabecular recesses. In this study, we aimed to identify the clinical characteristics of children with ventricular non-compaction and determine the factors affecting prognosis. We retrospectively evaluated 29 children with LVNC followed at Dr. Sami Ulus Children Hospital Pediatric Cardiology Department from December 2004 to November 2009. There were 13 females (45%) and 16 males (55%) and the mean age at presentation was 4.8±4.6 years (one month–15 years). Although there was no statistical significance; early presentation age and high left ventricular end-diastolic diameter at the diagnosis were associated with poorer prognosis.

Heart failure, Non-compaction of the left ventricle, Children

1. Introduction

Ventricular non-compaction (VNC) is a rare congenital cardiomyopathy characterized by prominent trabeculations and deep intratrabecular recesses in direct contact with the cavity [1]. The diagnosis of VNC is usually made by an echocardiographic (ECG). Since this cardiomyopathy can be easily overlooked during the echocardiography studies, it has become a frequently discussed subject [2]. Here, we aimed to determine the factors affecting prognosis and identify the clinical characteristics of children with VNC.

2. Materials and methods

We retrospectively evaluated 29 children with VNC followed at Dr. Sami Ulus Children's Hospital Pediatric Cardiology Department from December 2004 to November 2009. All patients' backgrounds and family histories were noted. Age and symptoms at presentation, gender-associated cardiac and extracardiac abnormalities and dysmorphic features were also recorded.

The diagnosis of VNC was made by ECG. The transthoracic ECG was performed with Vivid 7 (GE Healthcare, Milwaukee, WI, USA). The presence of a two-layered myocardium with a thicker non-compacted (NC) layer to a thin compacted (C) layer ratio >2 in the parasternal short axis or apical view, numerous excessively prominent trabeculations and deep intertrabecular recesses which were directly connected with the intraventricular cavity shown on color Doppler study were accepted as echocardiographic criteria of non-compaction. Echocardiograms were also used for calculating ejection fraction (EF), fractional shortening (FS), left ventricular end-diastolic diameter (LVEDD) and for detecting additional cardiac abnormalities. LVEDD beyond ±2 S.Ds confidence limit for age and body surface area was defined as left ventricular dilatation. When left ventricular EF and FS were below the standard values, it was termed a left ventricular systolic dysfunction.

All patients in this study were evaluated for arrhythmia. All had a twelve-lead ECG and a Holter examination was done when there was an abnormal ECG or in the case of suspected arrhythmia.

Left ventricular systolic functions before and after anticongestive therapy were compared and the factors which can affect the prognosis were evaluated.

All analyses were studied using SPSS 11.5 version (Chicago, IL, USA). A P<0.05 was accepted as statistically significant.

3. Results

Twenty-nine children with VNC followed at Dr. Sami Ulus Children's Hospital Pediatric Cardiology Department from December 2004 to November 2009 were observed. Of the 29 patients, 13 (45%) were female and 16 (55%) were male. Two were siblings and they had positive family history. The mean age at presentation was 4.8 years (one month–15 years). The mean follow-up period was 16 months (two months–four years).

The diagnosis of all patients was made by ECG studies. The regions most commonly involved were the left ventricular apical, inferior and lateral parts, respectively (Fig. 1 ).

Fig. 1.

Echocardiographic view of the involved area in left ventricle.

Left ventricular dilatation was seen in 25 patients (87%). Two patients (7%) showed no cardiomyopathic changes, one patient each (3%) had changes consistent with hypertrophic and restrictive cardiomyopathy (RCM) (Table 1 ).

Table 1

Patient dispersion according to the left ventricular morphology

Morphology	Number of
	patients (%)
LV dilatation	25 (87%)
Restrictive	1 (3%)
Hypertrophic	1 (3%)
No change	2 (7%)

At diagnosis, 25 patients (87%) had left ventricular systolic dysfunction and in the four (13%) remaining cases the left ventricular systolic function was in the normal range. At the time of presentation, the median value of EF was 44% and the median value of FS was 21%. None of the cases had intracardiac thrombosis.

Anticongestive and prophylactic anticoagulant therapy were given to the patients with left ventricular dilatation. We first used a loop diuretic and ace inhibitors. In some patients we added digital and aldactone according to the clinical condition.

In the younger age group, complaints like tachypnea, irritability, and growth retardation were more common while in the older age group fatigue and shortness of breath were the common symptoms. Clinical findings on admission were tachypnea, irritability, and growth retardation in nine patients (31%), cardiomegaly in four (14%), murmur in three (10%), dysmorphic facial appearance in two (7%), chest pain in two patients (7%). Two patients were detected during family screening (Table 2 ). Seven patients (24%) were previously diagnosed at different centers as having various forms of cardiomyopathies and all of them were admitted to the hospital with heart failure symptoms. These patient had previously been diagnosed with dilated cardiomyopathy (DCM) in six and RCM in one.

Table 2

Clinical presentations at the time of diagnosis

Clinical symptoms	Number of
	patients (%)
Heart failure symptoms	20 (69%)
Murmur	3 (10%)
Dysmorphic facial appearance	2 (7%)
Chest pain	2 (7%)
Asymptomatic	2 (7%)

In some patients, cardiac and extracardiac pathologies were present. In seven cases (24%) additional cardiac problems were detected. In five patients there was only one cardiac defect. Atrial septal defect (ASD), patent ductus arteriosus (PDA), Ebstein abnormality, aortic root dilatation and mitral valve prolapse (MVP) were present in each patient. Three patients had more than one additional cardiac anomaly: ASD and ventricular septal defect (VSD), Ebstein abnormality and VSD and VSD and endocardial fibroelastosis (EFE). The other 22 patients (76%) had isolated VNC. All of the additional cardiac disease was hemodynamically and clinically insignificant. We decided that none of them contribute to congestive heart failure.

Eight cases (28%) had extracardiac pathologies: five patients (17.2%) had mental and motor retardation, one (3.4%) had microcephaly, one (3.4%) had vesico-ureteral reflux (VUR) and one patient had (3.4%) lung cysts. These findings are shown in Table 3 . Two patients (7%) with dysmorphic appearance were referred to a different center for genetic research, these patients also had mental and motor retardation.

Table 3

Extracardiac pathologies in patients with VNC

Extracardiac pathology	Number of
	patients (%)
Mental and motor retardation	5 (17.2%)
Microcephaly	1 (3.4%)
Vesico-ureteral reflux	1 (3.4%)
Lung cysts	1 (3.4%)

VNC, ventricular non-compaction.

During the follow-up, six patients (21%) died. The causes of death were heart failure in four and severe pneumonia and septicemia in two. With anticongestive therapy, improvement of left ventricular (LV) systolic function was detected in 11 patients (38%). Among these patients, left ventricular systolic functions were still below normal values in three (10%) and in the normal range in eight (28%). Despite eligible anticongestive therapy, no change or worsening of left ventricular systolic functions was seen in five patients (17%). Seven patients (24%) left the follow-up. In addition, three patients (10%) also received carvedilol. On follow-up, one patient's left ventricular function reached normal levels, another died and another left the study.

Neither gender nor the presence of additional cardiac anomalies were found to be statistically significant in prognosis. Although there is no statistical significance, diagnosis at an early age and lower LV systolic function at the time of diagnosis were found to be slightly related to a poorer prognosis (Table 4 ).

Table 4

Factors that may affect the prognosis

Variable	P-value
Age	0.163
Gender	0.212
LV systolic function at the time of diagnosis	0.058
Presence of additional cardiac abnormalies	0.220

During the follow-up, a variety of arrhythmias were detected in eight patients (28%). Two children (7%) had sinus tachycardia, five (17%) had ventricular extrasystoles (VES) and one patient (3%) had ventricular tachycardia (VT). Three of these patients (11%) received antiarrhythmic treatment and responses to therapy were satisfactory in all. Propranolol, amiodarone and sotalol were used in each patients with VES, VES and VT, respectively. In two cases (7%) a permanent pacemaker was inserted because of heart failure at another center.

Six patients (21%) had a positive family history for cardiac failure. Of these patients, two were siblings and three patients had a history of sibling death caused by heart failure. One patient's brother had been followed up with a diagnosis of DCM in another center. Parents of eight patients (28%) were consanguineously related to each other.

4. Discussion

VNC have been described for the first time in 1990, by Chin and his colleagues [3]. Morphologically, papillary muscles are not well-developed in these patients, and non-compacted internal myocardial layers consist of more than 50% of the ventricular wall thickness. Accompanying EFE exists due to a microcirculation disorder.

VNC consists of approximately 9% of all childhood cardiomyopathies [4]. Our non-compaction patients were 11.3% of all patients that we followed up due to different cardiomyopathies. However, since the diagnostic criteria are subjective and VNC may be easily overlooked during the ECG examination as the apical segment which the disease most frequently involves is difficult to display in a transthoracic ECG and it is also frequently seen with well-known cardiomyopathies, such as DCM or hypertrophic cardiomyopathies (HCM), VNC can occur more frequently than predicted.

If VNC does not coexist with other cardiovascular pathologies it is called an ‘isolated’ VNC. Although the left ventricle is most commonly affected (62%), both ventricles can be influenced in some cases (22–38%) [5]. Of our patients, 22 (76%) had isolated VNC and only the left ventricle was affected in all of them.

Approximately 44% of the cases are familial, and in both groups, dysmorphic facial appearance, such as strabismus, micrognathia, psychomotor retardation and visual problems may be found [3]. In our cases the leading extracardiac anomaly was mental and motor retardation. When the disease is detected family screening is required [6]. Two of our patients (6.8%) were diagnosed during family screening.

Diagnosis is made by ECG studies. The diagnostic criteria was first described by Jenni et al. in 2001 [7]. These criteria have been modified in later publications [8]. Diagnostic criteria include at least four distinct trabeculation and intratrabecular recesses, primarily involving the apical, the mid-inferior and the mid-lateral regions, direct contact of the recesses with the ventricular cavity which is shown by color Doppler ECG, and the ratio of the broad non-compacted structure to thin compact structure above 2 on parasternal short-axis image. The last criteria is especially controversial in children. Studies conclude that if echocardiographically measured NC/C ratio is above 1.4, echocardiographic follow-up of the patient must be taken into consideration. Nevertheless, in all of our patients NC/C ratio was above 2.

The disease is most often confused with DCM by ECG findings. Differential diagnosis also includes hypertrophic and restrictive cardiomyopathies, EFE, myocarditis and arrhythmogenic right ventricular dysplasia. Similar myocardial structural changes have also been reported in cases of severe aortic stenosis and in patients with pulmonary atresia and in intact interventricular septum but these are pathologically different [9].

In 36% of the cases additional cardiac pathologies were demonstrated in various reports. Different septation defects, PDA, pulmonary stenosis and a cleft in the mitral valve are some of the reported examples [10]. In seven (24.1%) of our cases, associated cardiac defects including various septation defects and MVP, Ebstein anomaly and aortic root dilatation was detected. The presence of additional cardiac anomalies was not found to be a statistically significant factor affecting the prognosis.

Patients can get a diagnosis from the neonatal period to old age. In our group, the earliest diagnosis was at one-month of age, while the latest was in the 15th year of life; the latter was asymptomatic and the diagnosis was made during family scanning, by ECG. Like the other reported cases, male predominance (56–82%), was also seen in our patients (55%) [3].

Diagnosis might be made in an asymptomatic patient with reduced left ventricular function by ECG at randomly or at heart failure, arrhythmias and thromboembolic events can be the indications [11]. Clinical presentations at the time of diagnosis are summarized in Table 2. Seven cases (24%) had already been diagnosed as DCM, HCM or RCM in other medical centers and all of them were admitted to the hospital with heart failure symptoms.

The mechanism of systolic heart failure in patients with non-compaction is not very clear. Non-compacted myocardium is more sensitive to reduction of myocardial oxygen supply and the toxic effects of catecholamines. The number of involved segments seems to be major determinant of LV systolic dysfunction [12].

The mechanisms of arrhythmias in left ventricular hypertrabeculation (LVHT) are largely unknown. Arrhythmias rarely appear in children compared to adults, the most frequent type being VES. Also left- and right-axis deviation, supraventricular extrasystoles, atrial fibrillation, supraventricular tachycardia, Wolff–Parkinson–White syndrome, left bundle branch block and AV block are disorders encountered [13]. Subendocardial hypoperfusion and microcirculatory dysfunction are thought to be responsible for these arrhythmias [14]. Various types of arrhythmias were detected in eight (27.5%) of our cases.

Low EF, rhythm disturbances, and deep recesses may cause systemic embolism [15]. In our patients no thromboembolic event has been found.

Several studies showed that the younger age at diagnosis, NC/C ratio >3 and higher immediate LVEDDs, and more hypertrabecular segments seen in echocardiography have been associated with a poor prognosis [7]. In this study, no prognostic factor was found to impact statistically on the prognosis. But an early age and lower LV systolic function at the time of diagnosis seems to produce poor prognostic factors while older asymptomatic patients with normal-sized left ventricle at diagnosis seem to have a better prognosis. Lack of statistical significance may be related to the small number of patients who could be followed up.

5. Conclusions

Our non-compaction patients were 11% of all cases that we followed up because of different cardiomyopathies. In 27% of cases extracardiac diseases, mainly mental and motor retardation were found. The most common complaints at admission were due to heart failure (69%). The mortality rate was 21% and death was caused by cardiac failure and sepsis. No prognostic factor was found to be statistically important.

☆

Presented at the 6th Congress of Update in Cardiology and Cardiovascular Surgery – Heart and Health Foundation of Turkey (HHFT), Izmir, Turkey, April 15–18, 2010.