Pediatric idiopathic dilated cardiomyopathy: A single center experience.

CONTEXT: Idiopathic dilated cardiomyopathy (IDCM) is a severe illness with high mortality in the pediatric population. AIMS: To highlight our experience about clinical course and outcome of IDCM. SETTINGS AND
DESIGN: Patients' files were reviewed retrospectively for diagnosed cases of IDCM in the pediatric cardiology unit of King Abdul Aziz University Hospital, Jeddah, Saudi Arabia, from Jan 2003 to Jun 2011.
MATERIALS AND METHODS: Data about full history, clinical examination and investigations were recorded and grouped according to outcome as alive and well (group 1), alive and symptomatic (group 2) and worsened or dead (group 3). STATISTICAL ANALYSIS: Data was subjected to descriptive analysis. Chi-square and Student's paired t-test techniques were used where appropriate. Spearman rank correlation and survival analysis was done.
RESULTS: Eighty three patients were included with presenting age median (range), i.e.,14 (2 months-12 years) with females predominance 53 (63.9%). On presentation; cardiomegaly was noted in 72 (86.7%) with increased lung vascularity in 45 (54%). Sixty-one (74%) patients had ST segment and T-wave changes on electrocardiogram, while the same number had left ventricular hypertrophy, and 15 (18%) had arrhythmias. Echocardiography records on presentation and at last follow-up showed significant difference in several areas. Group 1 had 40 (48.2%), Group 2 had 23 (27.7%) while 20 (24.1%) were in Group 3 including nine cases who died. Survival rate over three years was 78%. Older the age, worse was the outcome (Spearman's rho = 0.3, P = 0.04).
CONCLUSION: Majority of subjects were presented during first year of life; the three year survival rate was 78%. Favorable outcome was correlated with younger age at presentation.

INTRODUCTION

Dilated cardiomyopathy (DCM) is a heterogeneous group of myocardial diseases characterized by cardiac dilatation and impaired myocardial contractility.[1] The annual incidence of DCM is between 0.34 and 0.73 per 100,000 children,[23] While in Qatar all types of cardiomyopathies in all age groups were 2.5-5.2/100,000 population from 1996 to 2003,[4] in Finland, the annual incidence of idiopathic dilated cardiomyopathy (IDCM) in children was 0.34 cases per 100,000 of the age-specific population.[5]

Although progress has been made in understanding its etiology, i.e., numerous infectious, metabolic, and mutation of myocardial protein that helped in diagnosis of pediatric DCM, still majority of cases remain undiagnosed and are hence designated as idiopathic.[236]

The prognosis is often poor, with 5-year mortality of up to 80% in pediatric cases; nevertheless, a high scale of variability has been observed in clinical pathway and morphologic and hemodynamic features,[3-8] which suggested the need to set up an optimal management protocol and classify predictors of prognosis more accurately.[78] However, to the best of our knowledge, data regarding the prognosis of DCM in Saudi children in Saudi Arabia and Gulf region is scarce. Such prognostic information is required for constructing better management protocols, either locally or globally.

This study aimed to highlight the clinical course and outcome of IDCM in pediatric patients.

MATERIALS AND METHODS

Patients’ files were reviewed retrospectively for those presented with diagnosis of IDCM in the pediatric cardiology unit of King Abdul Aziz University Hospital (a tertiary care hospital in Jeddah, Saudi Arabia) from Jan 2003 to Jun 2011.

All pediatric cases presented with left ventricular end-diastolic and end-systolic dimensions ≥ 2 standard deviations (SDs), which was greater than those established for a normal heart according to age and body surface area, and left ventricular ejection fraction or fractional shortening with at least 2 SDs ≤ 55% and ≤ 26%, respectively, were included.[9]

Patients with transient cardiac abnormalities (e.g., acute myocarditis) were excluded except those having abnormal cardiac size/function, or both, for ≥ six months. Diagnosed cases with secondary forms of myocardial disease were also excluded. During the study period, 130 patients diagnosed with DCM and 38 (29%) had some causes, i.e., anomalous left coronary artery origin (diagnosed by cardiac catheterization), sepsis, systemic diseases, severe peri-natal hypoxia, post diphtheria, uremia, coarctation and metabolic diseases.

Data regarding full history and clinical examination, i.e., chest X-ray, electrocardiography (ECG), echocardiography, Doppler using Hewlett Packard (Philips) SONOS 7500 Ultrasound Machine were collected.

Interventricular septum in diastole and systole (IVSd and IVSs), end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular dimension in diastole and systole (LVEDd and LVEDs), left ventricle posterior wall in diastole and systole (LVPd and LVPs). Stroke volume (SV), fractional shortening (FS) and ejection fraction (EF) were obtained digitally by echocardiography M-Mode.

Patients were managed by diuretics, angiotensin converting enzyme (ACE) inhibitors and digoxin with Aspirin (prophylactic dose) as initial therapy and were admitted in the hospital for intravenous inotropes if they deteriorated clinically. Anti-arrhythmic drugs were used if arrhythmias occurred. Data about patients’ follow-up visits were collected that usually scheduled at one to three months gaps according to patients’ clinical status and each visit had full clinical examination, ECG, chest X-ray and echocardiography.

Patients were grouped according to the outcome as alive and well (group 1), alive and symptomatic (group 2), and worsened or dead (group 3). Improved patients and an increase in the ejection fraction > 5% were defined as improved (group 1). Zero to ≤ 5% change in the ejection fraction was considered as stationary (group 2). Clinical worsening and/or decline in the ejection fraction > 5% was classified as deteriorated (group 3). The time of death from the first presentation was noted. Some patients who had a follow-up of < 3 months (unless dead) were classified as lost to follow-up and were also excluded from study. Patients were followed for 34.7 ± 23.2 months.

Ethical issues

Ethical review committee of the hospital has approved this study

I declare that I have no financial and/or personal relationship (s), which may have inappropriately influenced me in writing this paper.

Data analysis

The data were analyzed using SPSS version 10 (SPSS Inc., Chicago, IL, USA). Continuous data are expressed as median and range or mean ± standard deviation (SD) and categorical data as frequency percentages. Category variable differences were analyzed by Chi-square analysis. Differences in continuous variables by Student's paired t-test analyses and bivariate correlation analysis (spearman rank) was applied to assess patients’ age at presentation and outcome. Kaplan-Meier survival analysis was done. Probability values ≤ 0.05 were considered significant.

RESULTS

Eighty three patients of IDCM were included out of 92 as nine patients did not have the required follow-up. Age at presentation ranged from 2 month to 12 years with a median of 14 months with high frequency of females 53 (63.9%). Regarding history, 32 (39%) of patients had weight below the third percentile and 17 (20.5%) had family history of cardiac disease. Cardiomegaly (chest X-ray) was noted in 72 (86.7%) with increased lung vascularity in 45 (54%). Sixty-one (74%) patients had ST segment and T-wave changes on electrocardiogram while the same number had LVH, and 15 (18%) had arrhythmias. Patients mean follow-up was 34 ± 21 months [Table 1].

Table 1

Presenting clinical features, ECG and X-rays findings (N=83)

On comparing the echocardiography data, i.e., on presentation and at most recent follow-up using paired t-test, we found significant difference in several areas, i.e., EDs, ESV, LVPs, FS, SV and EF [Table 2].

Table 2

Echocardiography measurements on presentation and last follow-up

On the other hand, 40 (48.2%) improved, 23 (27.7%) were remained stationary and 20 (24.1) deteriorated, and out of deteriorated cases nine died. Survival rate over three years was 78% [Figure 1].

Figure 1

Kaplan-Meier survival analysis in 83 patients with idiopathic dilated cardiomyopathy

Age at the time of first presentation was positively correlated with outcome, i.e., older the age worse was the outcome (Spearman's rho = 0.3, P = 0.04).

DISCUSSION

Childhood DCM is a rare and debilitating disease of various etiologies with intense morbidity and mortality.[10] Principal indication for pediatric cardiac transplantation is considered as DCM.[11] A steadily improved outcome after cardiac transplantation has been found, but still there is a threat of demand and supply mismatch, as well as continual disquiet regarding midway and long-term morbidity and mortality.[12] Other issue of concern is the poor establishment of pediatric epidemiology and clinical course of DCM and majority remained undiagnosed in the context of cause, which confines the potential for disease-specific therapies.[10]

Majority of young children with female dominance are affected by disease, and indeed, 50% of presentations were before 14 months of age of the children studied here. In a nationwide Finnish study, 52% of IDCM occurred in the first year of life with male dominance.[5] High incidence of DCM < 1 year of age was also found in the studies of Towbin et al.[10] and AL Jarallah et al. in Riyadh, Saudi Arabia, i.e., (69.7%) with female predominance.[13] Median age at diagnosis was 2.5 years for children with male predominance was found in Kuwait and Egypt by Elkilany et al., while Venugopalan et al. found majority of cases of IDCM in younger children in Oman.[1415] Other presenting features were also comparable with the study of AL Jarallah et al.[13] These differences may be attributable to racial basis.

Seventeen patients (20.5%) in our study group had familial cardiomyopathy. Similarly, Venugopalan et al. demonstrated a prevalence of familial disease in 30%, while 14% was found by AL Jarallah et al., and other studies have shown > 30% genetic causes of DCM.[131617]

Over time we found the improvement of LVPs, LVEDs, ESV, SV, EF and FS. A significant difference could appear before first 6 months of diagnosis in case of LVEDs and FS, while it was not observed when LVEDd was analyzed.[5]

Nearly half of patients improved, which was comparable with the study of AL Jarallah et al., who found 37% improvement, 55.5% stationary and 7.4% deterioration.[13] In other studies, it has been found that after a 2.5 years of median follow-up period, about one-third of patients fully improved, 38% survived and had left ventricular dysfunction and 29.4% died, mostly in the first year of follow-up.[16]

Arola et al. revealed the survival rates after one, three and five years as 65%, 56% and 51%, respectively. Venugopalan et al. reported the survival rate of 94% at one year and 87% at three years in Omani children and it was 92% at one year by Elkilany et al. in children in Kuwait and Egypt.[51415]

Older age at presentation was a predictor of unfavorable outcome in children with idiopathic dilated cardiomyopathy. This is similar to results obtained by others who declared that age below two years at presentation has relation with good outcome.[18] Age was not found a predictive factor for outcome in other studies.[513]

CONCLUSION

Among the majority of subjects presented during first year of life, three year survival rate was 78%. About one quarter deteriorated and nine died. Favorable outcome was correlated with younger age at presentation. Further studies are necessary with high sample size to verify predictors of outcome in IDCM patients. Recognition of affecting markers of early myocardial function is vital for attaining improvements in treatments and consequently outcomes. New strategies to make new methods as functional as possible for early diagnosis and risk judgment are highly required.