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Pediatric cardiomyopathies over the last decade: a retrospective observational epidemiology study in a tertiary institute, Egypt

Elmasry, Ola A.; Kamel, Terez B.; El-Feki, Naglaa F.

The Journal Of The Egyptian Public Health Association: August 2011 - Volume 86 - Issue 3 and 4 - p 63–67
doi: 10.1097/01.EPX.0000399140.68151.6a
Original articles
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Background Pediatric cardiomyopathy (CM) is a rare, life-threatening disorder of unknown etiology. Data on CM in Egypt are scarce as there is no national registry. This study was an effort to understand the demographic features, clinical presentation, and frequency of different types of childhood CM in Egypt.

Materials and methods Medical files of all children diagnosed with CM in the last decade (1997–2007) and referred to the Pediatric Cardiology Clinic at Ain Shams University, Children's Hospital (Cairo, Egypt), were reviewed. This study included 124 (6.6%) cardiomyopathic patient files from a total of 1876 cardiac patients that were followed up at the Pediatric Cardiology Clinic during the 10-year study period.

Results In the last decade (1997–2007), children with CM represented 6.6% of all children with cardiovascular diseases followed at the Pediatric Cardiology Clinic; 73 were boys (58.9%) and 51 were girls (41.1%), with a mean age of 3.82±3.99 years. Parental consanguinity was positive in 19.4% of patients and a history of preceding viral infection was present in one patient (0.8%). Eight patients had a similarly affected sibling (6.5%).

Conclusion and recommendations Data on CM in Egypt are scarce, highlighting the urgent need for a national registry for CM (a) to allow more accurate assessment of the size of this problem, especially in children; (b) to minimize loss of follow-up data when patients move from one region to another; and (c) to allow screening of family members of a proband case.

Department of Pediatrics, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt

Correspondence to Dr Terez B. Kamel, Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt Tel: +2 02 24843479; fax: +2 02 24820237; e-mail: terez2003@hotmail.com

Received January 23, 2011

Accepted April 4, 2011

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Introduction

Pediatric cardiomyopathies (CMs) are a heterogeneous group of conditions, of which dilated CMs are the most common subtype. However, the etiology and pathogenesis of many cases remain unknown [1]. The prevalence of CM in the newborn period is 10/100 000 live births, whereas for all children the prevalence is 36/100 000 for dilated CM and 2/100 000 for hypertrophic and restrictive CM [2].

In Africa, CMs pose the greatest challenge of all the cardiovascular diseases because of their greater prevalence in societies still plagued by diseases of famine and pestilence; because of the difficulty in diagnosis, which often requires specialized investigations that are lacking in resource-poor environments; and because of the lack of access to effective interventions, such as heart transplantation [3]. Observational epidemiology had notable success in identifying many modifiable exposures that apparently increase or decrease the risk of diseases [4]. Data on CM in Egypt are scarce as there is no national registry. Therefore, this retrospective study aimed to describe the common features of children diagnosed with CM during the last decade in an effort to understand the demographic features, clinical presentation, and frequency of occurrence of different types of CM in children with CM in Egypt.

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Materials and methods

This retrospective study was conducted from January 2008 till January 2009. Medical files of all children diagnosed with CM and referred to the Pediatric Cardiology Clinic at Ain Shams University, Children's Hospital (Cairo, Egypt) in the last decade (1997–2007), were reviewed. The study was ethically approved by the Pediatric Departmental Board.

This study included 124 (6.6%) cardiomyopathic patient files from a total of 1876 cardiac cases that were followed at the Pediatric Cardiology Clinic during the 10-year study period.

Medical files were reviewed with regard to the demographic features (e.g. age at diagnosis, sex, residence, and consanguinity) and initial clinical presentation (e.g. difficulty of breathing, pallor, palpitation, cyanosis, and/or chest pain). Parameters collected from the echocardiogram determined the type of CM (dilated CM, hypertrophic CM, restrictive CM, etc.), medications received, and duration/frequency of follow-up.

An IBM computer using statistical program for social science version 15 (Chicago, Illinois, USA) analyzed the data as follows: quantitative variables as mean [standard deviation (SD)] and range and qualitative variables as number and percentage. The χ2-test and the Fisher's exact test were performed. P values of 0.05 or less were considered statistically significant.

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Results

During the period from January 1997 to January 2007, 1876 patients with cardiac disease were referred to the Pediatric Cardiology Clinic at the Children's Hospital. CM was confirmed by echocardiography in 124 children (6.6%) (CM group). The average annual occurrence of new CM cases enrolled per year of the study is demonstrated in Fig. 1. The mean frequency±SD of follow-up per year was 7.76±6.84 visits and the annual incidence of CM was 1.24 per 100 000 children younger than 10 years.

Figure 1

Figure 1

The CM group included 73 boys (58.9%) and 51 girls (41.1%), with a male-to-female ratio of 2.8:2. Their age ranged from 1 month to 14 years, with a mean±SD of 3.82±3.99 years; 24 children (19.3%) presented in their first year of life, whereas 46 children (45.5%) were between 1 and 6 years of age. The majority of patients had dilated CM (n=78; 88.7%). Hypertrophic CM was present in 10 patients (9.7%), whereas restrictive CM was found in two patients (1.6%). Slightly more than half the patients with CM (51.6%) were referred from the Cairo Governorate. Parental consanguinity was present in 24 patients (19.4%), and a definite history of a preceding viral infection was present in one patient (0.8%) (Table 1).

Table 1

Table 1

A positive history of chemotherapy for malignancy was present in two patients (Ewing's sarcoma, acute lymphoblastic leukemia), and both had dilated CM. Eight patients (6.5%) had a similarly affected sibling. Nineteen patients (15.3%) had coexisting extracardiac disease (Table 2).

Table 2

Table 2

Symptoms at presentation in the order of frequency were difficulty in breathing (n=45; 36.3%), cough (n=11; 8.9%), palpitations (n=7; 5.6%), and recurrent chest infections (n=6; 4.9%). Cyanosis was the presenting complaint in four children (3.2%) (Table 3).

Table 3

Table 3

There were no statistically significant differences observed between patients with dilated CM and patients with hypertrophic CM as regards age distribution, sex, or clinical presentation (P>0.05) (Table 4). The Majority of patients were on regular diuretic therapy (n=88; 70%), whereas 73 patients (58.9%) received digoxin therapy and 72 children (58.1%) were on angiotensin-converting enzyme inhibitor. Sixty-seven patients (53.6%) received regular antiplatelet therapy (aspirin) whereas 18 patients (14.5%) were on formal anticoagulation (warfarin).

Table 4

Table 4

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Discussion

CMs represent a major cause of morbidity and mortality in both children and adults and are the most frequent indication for cardiac transplantation [5]. Although dilated CM is the most common form of CM and the most common cause of cardiac transplantation, its epidemiology and clinical course are still not well established [6]. Moreover, despite the billions of dollars spent on the care of these patients, the development of new therapies, and the genetic-based studies, survival is still poor [7]. During the period January 1997–2007, 124 out of 1876 children (6.6%) referred to the Pediatric Cardiology clinic, Ain Shams University, had CM. Nugent et al. [8] reported 314 new cases of CM over a 10-year period (1987–1996) in Australia, diagnosed according to WHO guidelines [9]. In this study, the annual incidence of CM was 1.24 per 100 000 children younger than 10 years of age, similar to that reported by Nugent et al. in Australia [8] and similar to the 1.13 per 100 000 reported in a North-American study [10].

Although these values exceed the incidence of 0.74 per 100 000 reported in the Finnish study [11], the exclusion of individuals with self-limiting CM from the Finnish study may explain these differences. However, these data do not represent a true national incidence of CM in view of the lack of a national CM registry in Egypt; based on the number of centers caring for children with cardiac disease in Cairo alone, this patient population may reflect the distribution and variety of pediatric cardiac diseases in Egypt. In this study, the age at presentation of pediatric CM ranged from 1 month to 14 years, with a mean age of 3.8 years. Previous studies [12–14] have shown that the mean age of onset of pediatric CM ranges from 1.5 to 2.3 years. The majority of studied patients (45.5%) were between 1 and 6 years of age at presentation. Dilated CM was reported to occur more often in the first year of life than in older pediatric age groups [13]. The older age at presentation in this study may represent a true difference in the epidemiology of CM in Egyptian children, but more likely may be a consequence of delayed diagnosis and high mortality-associated with CM in the first year of life [15].

Similar to previous studies [8,13,14,16], there was a preponderance of boys with a male-to-female ratio of 2.8 : 2. Patients in this study were referred from different governorates in Egypt. Just over half of them (51.5%) were from Cairo, which is probably due to (a) the high population density in the capital area, (b) their proximity to the center, (c) the better health services, and (d) better reporting. The fact that approximately 48% of the patients were from distant governorates may have contributed to the low availability of follow-up data in the files and to the reduced frequency of follow-up, as most of the parents of these patients would prefer to follow-up closer to their homes than travel to the capital every 1 to 3 months.

A history of previous viral infection was reported in only one case, which was diagnosed as viral myocarditis. Although other studies have reported a similarly low incidence of viral myocarditis [17], viral myocarditis is reportedly more important in childhood CM than in adults [16–18]. However, diagnosis of myocarditis is problematic owing to sampling limitation and variation in histopathological diagnostic criteria [19].

In this study, cytotoxic-induced CM secondary to treatment of malignancy (doxorubicin) was present in two patients (2.5%). This is similar to the reported incidence of cytotoxic-induced CM in other studies [10,20]. Doxorubicin, a broad-spectrum antitumor antibiotic, has been widely used in the treatment of several cancers. Doxorubicin-associated CM and congestive heart failure are dose-dependent and the incidence of these complications rise to unacceptably high levels when the cumulative dose of the drug is greater than 360 mg/m2 of body surface area [20].

Parental consanguinity was documented in 19.4% as a potential marker of recessively inherited conditions. Nugent et al. [8] reported consanguinity in only 6.7% in their study. Arab populations have a long tradition of consanguinity due to sociocultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first-cousin marriages, which may reach 25–30% of all marriages [21]. Consanguinity has been a long-standing social habit among Egyptians. Estimates of consanguinity ratios in different parts of Egypt ranged from 29 to 50% [21,22]. Data on genetic disorders in Arab populations, as extracted from the Catalogue of Transmission Genetics in Arabs database, indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity [21]. Despite the higher rate of parental consanguinity, CM in another sibling was positive in only eight children (6.4%) in this patient population, in contrast to 19.7% found by Nugent et al. [8] and to 23% reported in the Finnish study [11]. Although this could be due to underreporting, it might also reflect a difference in the underlying cause and in the mode of inheritance of the CMs in the studied population.

Extracardiac manifestations were found in 15.3% of studied patients (n=19; total=124) in this study. The length of the study period allowed incorporation of advanced investigations for the diagnosis of genetic, infectious, and metabolic abnormalities into the clinical protocols. Absence of these investigations in the early years of the study would have limited the diagnosis of extracardiac diseases in this patient population. Nugent et al. [8] reported that 28.8% of their studied patients with CM had an underlying syndrome, including Noonan's syndrome, Leber's disease, Costello's syndrome, Beckwith–Wiedemann syndrome, and Fukuyama's syndrome, in addition to 1.9% with multiple congenital extracardiac abnormalities of no definable syndrome. Moreover, 28 of the 314 children in their study (8.9%) had a metabolic disease etiologically linked to CM.

The main presenting symptoms were difficulty in breathing (36.3%), cough (8.9%), and chest infection (13.7%). Durani et al. [23] reported that children with dilated CM most commonly present with difficulty in breathing. This is in keeping with previous studies that reported symptoms of congestive heart failure in 89.7% of patients [24]. Myocarditis and dilated CM may mimic other respiratory or viral illnesses, but hepatomegaly or the finding of cardiomegaly and an abnormal electrocardiogram result may help to distinguish these diagnoses from other more common pediatric illnesses [23].

Dilated CM was the most frequent type of CM present in 108 children (87.1%). Hypertrophic CM was found in 10 cases (9.7%). Dilated CM is the most common type of CM accounting for 53.8–90% of all patients with CM referred to specialized centers [14,25–27].

In this study's center, treatment of dilated CM was essentially the treatment of heart failure, applying the classic treatment algorithms for heart failure with and without reduced ejection fraction. Treatment is based on measures offloading the heart (angiotensin-converting enzyme inhibitors, β-blockers, diuretics) and on antiarrhythmic and anticoagulation, when needed [28]. The use of angiotensin-converting enzyme inhibitors has been reported to be associated with improvement of left ventricular dysfunction in children [29]. Preliminary evidence also indicates that β-blocker therapy can improve left ventricular dysfunction in pediatric dilated CM [30]. Aspirin remains the most common antiplatelet agent used in pediatrics. The dose of aspirin for optimal inhibition of platelet aggregation is not known, although empiric low doses of 1–5 mg/kg/day have been proposed [31]. The relatively low doses of aspirin used as antiplatelet therapy, as compared with the much higher doses used for anti-inflammatory therapy, seldom cause other side effects. Although aspirin is associated with Reye syndrome, this appears to be a dose-dependent effect of aspirin and is usually associated with doses greater than 40 mg/kg [32–36].

In a cross-sectional study, on CM children awaiting cardiac transplant, 31% were said to have acute pulmonary embolism confirmed by ventilation/perfusion scan or angiography [37]. There are no studies on anticoagulant prophylaxis in pediatric patients. However, based on adult studies and the apparent risk of pulmonary embolism and stroke in children with CM, primary prophylaxis with warfarin (target international normalized ratio 2.5; range: 2.0–3.0) is often used [38]. Moreover, Monagle et al. [39] suggested that pediatric patients with CM should receive vitamin K antagonists to achieve a target international normalized ratio of 2.5 (range: 2.0–3.0) no later than their activation on a cardiac transplant waiting list (Grade 2C evidence).

After 200 years of use [40], digitalis still appears to have a place in this armamentarium for heart failure, despite the proven survival benefits with angiotensin-converting enzyme inhibitors and β-blockers. Digoxin therapy is inexpensive and well tolerated, and it may result in considerable savings. Digoxin is the only oral inotrope that does not increase mortality in patients with heart failure, particularly if low doses are being used. It can be used in patients with systolic heart failure despite therapeutic doses of angiotensin-converting enzyme inhibitors or diuretics or in patients with atrial fibrillation with or without heart failure for rate control [40]. The absence of heart transplantation as a therapeutic option for children with dilated CM in Egypt makes it imperative to use all available treatment options. New therapies for the treatment of adult heart failure need to be extended to the treatment of pediatric dilated CM, as has been suggested by other investigators [41].

This study is limited by the fact that it is representative of only one center's data on CM in Egyptian children and by the absence of follow-up data in a large number of files due to infrequent patient follow-up.

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Conclusion and summary

This retrospective review of children referred with cardiac disease over the past decade has shown that CM represents 6.6% of all cardiac diseases in study center. The majority of children presented between 1 and 6 years of age, and CM was more common in boys. Dilated CM was the most common type of CM (88.7%). Parental consanguinity was positive in almost a fifth of the patients and concomitant extracardiac disease was found in 15.3% of children (n=19; total=124). Treatment of CM was symptomatic. This study highlights the importance of a national registry for CM in Egypt, which would allow a more accurate assessment of the size of this problem, especially in children, would minimize the loss of follow-up data when patients move from one region to another, and would allow screening of family members of a proband case.

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Keywords:

cardiomyopathy; children, Egypt

© 2011 Egyptian Public Health Association