Cardiology in the Young (2015), 25, 333–337
© Cambridge University Press, 2014
doi:10.1017/S1047951113002369
Original Article Paediatric dilated cardiomyopathy: clinical profile and outcome. The experience of a tertiary centre for paediatric cardiology Joana O. Miranda,1 Liane Costa,2 Esmeralda Rodrigues,3 Elisa L. Teles,3 Maria J. Baptista,1 José C. Areias1 1
Department of Paediatric Cardiology; 2Department of Pediatrics; 3Department of Pediatrics, Metabolic Diseases Unit, Centro Hospitalar São João, Porto, Portugal Abstract Dilated cardiomyopathy is the most common form of cardiomyopathy in the paediatric population and an important cause of heart transplantation in children. The clinical profile and course of dilated cardiomyopathy in children have been poorly characterised. A retrospective review of 61 patients (37 female; 24 male) diagnosed with dilated cardiomyopathy from January, 2005 to June, 2012 at a single institution was performed. The median age at diagnosis was 15 months. Heart failure was present in 83.6% of patients and 44.3% required intensive care. The most prevalent causes were idiopathic (47.5%), viral myocarditis (18.0%) and inherited metabolic diseases (11.5%). In viral myocarditis, Parvovirus B19 was the most common identified agent, in concurrence with the increasing incidence documented recently. Inherited metabolic diseases were responsible for 11.5% of dilated cardiomyopathy cases compared with the 4–6% described in the literature, which reinforces the importance of considering this aetiology in differential diagnosis of paediatric dilated cardiomyopathy. The overall mortality rate was 16.1% and five patients underwent heart transplantation. In our series, age at diagnosis and aetiology were the most important prognosis factors. We report no mortality in the five patients who underwent heart transplantation, after 2 years of follow-up. Keywords: Dilated cardiomyopathy; heart failure; paediatric cardiology; heart transplant; myocarditis; metabolic disease Received: 15 March 2013; Accepted: 15 December 2013; First published online: 15 January 2014
D
ILATED CARDIOMYOPATHY IS THE MOST COMMON
form of cardiomyopathy in paediatric population, with an annual incidence of 1.13/ 100,000 infants and children.1 It is a myocardial disorder characterised by a dilated left ventricular chamber and systolic dysfunction. Right ventricular dysfunction can also be noticed, increasing disease severity.2 Although rare, dilated cardiomyopathy is a common cause of heart failure in children and it is also the most common cause of heart transplantation in children older than 1 year of age.3 Unlike adults, whose main cause is coronary heart disease, the aetiology in the paediatric population is Correspondence to: J. O. Miranda, Department of Paediatric Cardiology, Centro Hospitalar São João. Alameda Prof. Hernâni Monteiro, 4202–451 Porto, Portugal. Tel: + 351 225512100; Fax: + 351225512273; E-mail: [email protected]
mainly idiopathic or due to myocarditis, inherited metabolic diseases, neuromuscular diseases and malformative syndromes.2,4 The demographics and underlying causes of paediatric dilated cardiomyopathy are not well characterised, particularly in our country. A better understanding of the epidemiology, aetiology and outcome of the disease would facilitate planning and provision of medical services. The aim of the study was to provide a detailed description of clinical profile and outcome of dilated cardiomyopathy in children.
Methodology We performed a retrospective review of children diagnosed with dilated cardiomyopathy from January, 2005 to June, 2012 in a tertiary centre of Paediatric
334
February 2015
Cardiology in the Young
Clinical presentation The majority of the patients had clinical evidence of heart failure at diagnosis [n = 51 (83.6%)]. Of all, 44.3% (n = 27) needed to be admitted to an intensive care unit. The need for intensive care admission was significantly higher in younger patients (21.0 months versus 63.7 months, p = 0.009). Family history of dilated cardiomyopathy and sudden death were observed in two patients, each. A measured left ventricular ejection fraction at clinical presentation was available for 85.2% of patients; in the remaining patients, there was qualitative information of reduced left ventricular systolic function. The mean left ventricular ejection fraction was 32.0% (standard deviation ±13.0%). Left ventricular ejection fraction ⩽30% was observed in 23 patients (37.7%), between 30% and 50% in 24 patients (39.3%) and >50% in five patients (8.2%). Patients admitted to an intensive care unit had a significantly lower mean left ventricular ejection fraction at presentation (mean −8%, p = 0.026).
Cardiology. All patients were examined by a paediatric cardiologist and data reported were based on comprehensive chart review of each patient visit. Demographic data, clinical presentation, aetiology, treatment and outcome were assessed. The diagnostic criteria for dilated cardiomyopathy were (i) reduced left ventricular systolic function on any form of cardiac imaging in patients with symptoms or a family history of dilated cardiomyopathy, (ii) a measured left ventricular ejection fraction 2 years Ejection Fraction average (SD) Hospital admission [n (%)] Intensive care admission [n (%)]
Other (n = 12) Idiopathic [n = 29 Myocarditis [n = 11 Inherited metabolic Neuro-muscular diseases (47.5%)] (18.0%)] diseases [n = 7 (11.5%)] [n = 2 (3.3%)]
Outcome The overall mortality rate was 16.1% (n = 10) (Table 2). The median age at death was 6.5 years and median time interval from the diagnosis to death was about 7.5 months (IQR 60.8 months). The mortality was significantly higher in patients under 1 year of age (32.0% versus 5.6%, p = 0.006). Analysing the outcome by the composite endpoint of death and/or transplantation according to the aetiologies subgroups, the subgroup with a significantly better outcome was the myocarditis group, with no deaths or transplants registered (0% versus 30% in the remaining subgroups, p = 0.036). The aetiological subgroup with higher mortality and/or transplantation, although not statistically significant, was the idiopathic subgroup (16.4% versus 8.2% in the remaining subgroups, p = 0.079). Within inherited metabolic disease causes, only one patient died (Barth Syndrome patient) (Table 2). In all, five patients underwent heart transplantation: two of them in other centres and three of them in our centre – an idiopathic form, a familial form and a left ventricular non-compaction disease; the median age at transplantation was 11.7 years. After 2 years of follow-up, no mortality was observed in transplanted patients.
Table 2. Characteristics at diagnosis and outcome of 61 patients with Dilated cardiomyopathy (DCM), by aetiology.
Therapy At the time of dilated cardiomyopathy diagnosis, 82.0% (n = 50) of the patients were started on anticongestive medication, 80.3% (n = 49) received an angiotensin-converting enzyme inhibitor and 72.1% (n = 44) antiaggregant therapy. Antiarrhythmic agents and inotropes were used on 29.5% (n = 18) of cases, each. There was a lower use of β-blockers [n = 11 (18.0%)] and calcium channel blockers [n = 1 (1.6%)]. Pacemaker and ventricular assist device were rarely used [n = 2 (3.3%) and n = 1 (1.6%), respectively]. Ventricular assist device was used only in one patient, as a bridge to transplantation.
p-value*
Of all patients, 50.7% (n = 31) were evaluated at inherited metabolic diseases consultation. Inherited metabolic diseases identified were: three cases of mitochondrial citopathies – including one Barth Syndrome – two cases of fatty acid oxidation disease (long-chain acyl CoA dehydrogenase deficiency) and two cases of lysosomal storage diseases (Mucopolysaccharidosis type I and type VI). In the majority (n = 5/7), dilated cardiomyopathy presentation preceded the inherited metabolic disease diagnosis. Duchenne and Becker muscular dystrophy were the two neuromuscular diseases identified. The polymalformative syndrome associated with dilated cardiomyopathy was Jacobsen Syndrome.
Total (n = 61)
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Among not transplanted survivors, the median follow-up time from diagnosis of dilated cardiomyopathy was 35.5 months (IQR 51.3 months). Of those, 24.6% (n = 15) maintained cardiac dysfunction despite pharmacological therapy and 36.1% (n = 22) had normalisation of cardiac function.
Discussion Dilated cardiomyopathy is an important cause of heart failure in children and, although a variety of aetiological factors have been investigated, a significant proportion of our patients with documented dilated cardiomyopathy did not have a demonstrable cause. In fact, almost half of our patients had an idiopathic form of dilated cardiomyopathy. In the literature, an idiopathic form of dilated cardiomyopathy is usually reported in about two-thirds to a half of the children.1,4,7 Viral myocarditis is an important, and often unrecognised, cause of dilated cardiomyopathy. The exact incidence of myocarditis is difficult to ascertain as the viral evaluation by polymerase chain reaction, although performed in most clinically suggestive cases, was not performed in all patients. Despite that, a high prevalence of Parvovirus B19 was observed in our population. In fact, the epidemiology of viral myocarditis has been changing in the past few decades. After 1995, as the prevalence of enterovirus decreased, the prevalence of adenovirus increased.8,9 More recently, Parvovirus B19 is reported as the most commonly detected viral genome. Whereas the pathogenic role of enterovirus and adenovirus in myocarditis and dilated cardiomyopathy is well established, the role of Parvovirus B19 is uncertain. Whether it is an incidental or a pathogenic agent in acute myocarditis is still unclear.10–12 In our series, a significant proportion of cases caused by inherited metabolic diseases was identified, 11.5% of the cases when compared with the 4–6% described in the literature.4,13,14 This evidence is probably due to the high rate of metabolic diseases investigation. These data reinforce the importance of considering inherited metabolic diseases in the differential diagnosis of children presenting with dilated cardiomyopathy, as it is crucial to define prognosis. The ideal time to diagnose inherited metabolic diseases is obviously the neonatal period, before clinical manifestations, using newborn screening followed by confirmatory studies. However, as three of our patients had mitochondrial citopathies, not included in the neonatal screening, and long-chain acyl CoA dehydrogenase deficiency patients were born before the inclusion of the disease in the neonatal screening, the majority of our patients had identification of the
February 2015
metabolic disease in the aetiological study for dilated cardiomyopathy. Recent population data from several groups have improved our understanding about the natural history of dilated cardiomyopathy. The Paediatric Cardiomyopathy Registry in North America showed a 5-year survival rate of 54% for dilated cardiomyopathy.14 The National Australian Childhood Cardiomyopathy Study showed 5-year freedom from death or transplantation of 63% for children with dilated cardiomyopathy.7 The predictors of survival for dilated cardiomyopathy vary considerably between series. The most consistent risk factors at diagnosis for subsequent death or transplantation are age, congestive heart failure, lower fractional shortening and ejection fraction and aetiology of dilated cardiomyopathy.4,18,19 In our study, age at diagnosis and aetiology were the most important prognosis factors. We observed that younger patients had worse prognosis: the younger the patient the greater the need for intensive care (p = 0.009) and, additionally, patients under 1 year of age presented higher mortality (p = 0.006). Aetiology also presented as an important prognostic factor. In fact, it is essential to establish the aetiology of dilated cardiomyopathy to determine the subsequent optimal management and more accurate prognosis. The idiopathic forms of dilated cardiomyopathy have a significant impact on morbidity and mortality in paediatric population. The overall prognosis of idiopathic forms tends to be poor, with a reported 5-year mortality rate in the literature of about 14–50%, from either sudden cardiac death or pump failure.1,7,15,16 In our population, the mortality rate of this specific subgroup was of 24%, thus superior to overall mortality of 16.1%. The worse prognosis associated with idiopathic forms, in comparison to other causes of dilated cardiomyopathy, raises questions about its optimal management: should these patients go through a more exhaustive aetiological study or should they undergo heart transplantation sooner? On the other hand, the outcome of viral myocarditis in children is superior. Studies have shown survival rates of between 75% and 100% for acute myocarditis in childhood.17 In our patients, viral myocarditis resulted in no mortality or transplantation. This emphasises the benefit of knowing the diagnosis of myocarditis, as acute transplantation should be avoided, even if mechanical support is required. This will provide the opportunity for cardiac recovery, as well as minimise the risks of transplantation during recent or active viral infection.18 With regard to treatment, anticongestive agents, angiotensin-converting enzyme inhibitors and antiaggregant therapy were the most commonly used drugs.
Vol. 25, No. 2
Miranda et al: Paediatric dilated cardiomyopathy
Pacemaker and ventricular assist device were rarely used. When acute heart failure is unresponsive to aggressive medical management, institution of mechanical circulatory support must be considered, sometimes as a bridge to transplantation. Heart transplantation remains the main therapy for end-stage heart failure refractory to surgical and medical therapy in children. In the literature, current 1-year survival after heart transplantation in children is 85%; the overall survival rate 20 years after transplantation is 40%.20 With a modest experience in paediatric heart transplantation, we report no mortality in patients who underwent transplantation, after 2 years of follow-up. The present report reflects the reality of the referral network of our tertiary centre, representing an overview of paediatric dilated cardiomyopathy. The observational and retrospective nature of the study constitutes a limitation. The centralisation of paediatric tertiary services provides a great opportunity to examine the presentation and natural history of this rare condition. A comprehensive analysis of data obtained from different observational studies can expand our understanding about the natural history of dilated cardiomyopathy in the paediatric population.
Acknowledgements None.
Financial Support This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
3.
4.
5.
6. 7.
8.
9.
10.
11.
12.
13.
14.
Conflicts of Interest 15.
None.
References 1. Lipshultz SE, Sleeper LA, Towbin JA, et al. The incidence of paediatric cardiomyopathy in two regions of the United States. N Engl J Med 2003; 348: 1647–1655. 2. Maron BJ, Towbin JA, Thiene G, et al. American Heart Association Council on Clinical Cardiology, Heart Failure and Transplantation, Council on Clinical Cardiology, Heart Failure and Transplantation Committee, Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups, and Council on Epidemiology and Prevention. Contemporary definitions and classifications of the cardiomyopathies: an American Heart Association scientific statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee;
16.
17. 18.
19.
20.
337
Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006; 113: 1807–1816. Boucek MM, Waltz DA, Edwards LB, et al. Registry of the International Society for Heart and Lung Transplantation: ninth official paediatric heart transplantation report. J Heart Lung Transplant 2006; 25: 893–903. Towbin JA, Lowe AM, Colan SD, et al. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA 2006; 296: 1867–1876. Daubeney PE, Nugent AW, Chondros P, et al. National Australian Childhood Cardiomyopathy Study. Clinical features and outcomes of childhood dilated cardiomyopathy: results from a national population-based study. Circulation 2006; 114: 2671–2678. Baughman KL. Diagnosis of myocarditis: death of Dallas criteria. Circulation 2006; 113: 593–595. Nugent A, Daubney PE, Chondros P, et al. National Australian Childhood Cardiomyopathy Study. The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med 2003; 348: 1639–1646. Bowles NE, Ni J, Kearney DL, et al. Detection of viruses in myocardial tissues by polymerase chain reaction: evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol 2003; 42: 466–472. Schultz JC, Hilliard AA, Cooper LT Jr, Rihal CS. Diagnosis and treatment of viral myocarditis. Mayo Clin Proc 2009; 84: 1001–1009. Kühl U, Pauschinger M, Seeberg B, et al. Viral persistence in the myocardium is associated with progressive cardiac dysfunction. Circulation 2005; 112: 1965–1970. Mahrholdt H, Wagner A, Deluigi CC, et al. Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation 2006; 114: 1581–1590. Kindermann I, Kindermann M, Kandolf R, et al. Predictors of outcome in patients with suspected myocarditis. Circulation 2008; 118: 639–648. Cox GF. Diagnostic approaches to paediatric cardiomyopathy of metabolic genetic etiologies and their relation to therapy. Prog Pediatr Cardiol 2007; 24: 15–25. Wilkinson JD, Landy DC, Colan SD, et al. The paediatric cardiomyopathy registry and heart failure: key results from the first 15 years. Heart Fail Clin 2010; 6: 401–413; vii. Friedman RA, Moak JP, Garson A. Clinical course of idiopathic dilated cardiomyopathy in children. J Am Coll Cardiol 1991; 18: 152–156. Arola A, Tuominen J, Ruuskanen O, et al. Idiopathic dilated cardiomyopathy in children: prognostic indicators and outcome. Paediatrics 1998; 101: 369 –376. English RF, Janosky JE, Ettedgui JA, et al. Outcomes for children with acute myocarditis. Cardiol Young 2004; 14: 488–493. Feingold B, Webber SA. Acute myocarditis and cardiomiopathies. In: Munoz R, Morell V, Cruz Ed, Vetterly C (eds) Critical Care of Children with Heart Disease: Basic Medical and Surgical Concepts, 1st edn. Springer, London, 2010, pp. 507–520. Alvarez JA, Wilkinson JD, Lipshultz SE. Outcome predictors for paediatric dilated cardiomyopathy: a systematic review. Prog Pediatr Cardiol 2007; 23: 25–32. Hsu DT, Pearson GD. Heart failure in children: part II: diagnosis, treatment, and future directions. Circ Heart Fail 2008; 2: 490–498.
© Cambridge University Press, 2014
doi:10.1017/S1047951113002369
Original Article Paediatric dilated cardiomyopathy: clinical profile and outcome. The experience of a tertiary centre for paediatric cardiology Joana O. Miranda,1 Liane Costa,2 Esmeralda Rodrigues,3 Elisa L. Teles,3 Maria J. Baptista,1 José C. Areias1 1
Department of Paediatric Cardiology; 2Department of Pediatrics; 3Department of Pediatrics, Metabolic Diseases Unit, Centro Hospitalar São João, Porto, Portugal Abstract Dilated cardiomyopathy is the most common form of cardiomyopathy in the paediatric population and an important cause of heart transplantation in children. The clinical profile and course of dilated cardiomyopathy in children have been poorly characterised. A retrospective review of 61 patients (37 female; 24 male) diagnosed with dilated cardiomyopathy from January, 2005 to June, 2012 at a single institution was performed. The median age at diagnosis was 15 months. Heart failure was present in 83.6% of patients and 44.3% required intensive care. The most prevalent causes were idiopathic (47.5%), viral myocarditis (18.0%) and inherited metabolic diseases (11.5%). In viral myocarditis, Parvovirus B19 was the most common identified agent, in concurrence with the increasing incidence documented recently. Inherited metabolic diseases were responsible for 11.5% of dilated cardiomyopathy cases compared with the 4–6% described in the literature, which reinforces the importance of considering this aetiology in differential diagnosis of paediatric dilated cardiomyopathy. The overall mortality rate was 16.1% and five patients underwent heart transplantation. In our series, age at diagnosis and aetiology were the most important prognosis factors. We report no mortality in the five patients who underwent heart transplantation, after 2 years of follow-up. Keywords: Dilated cardiomyopathy; heart failure; paediatric cardiology; heart transplant; myocarditis; metabolic disease Received: 15 March 2013; Accepted: 15 December 2013; First published online: 15 January 2014
D
ILATED CARDIOMYOPATHY IS THE MOST COMMON
form of cardiomyopathy in paediatric population, with an annual incidence of 1.13/ 100,000 infants and children.1 It is a myocardial disorder characterised by a dilated left ventricular chamber and systolic dysfunction. Right ventricular dysfunction can also be noticed, increasing disease severity.2 Although rare, dilated cardiomyopathy is a common cause of heart failure in children and it is also the most common cause of heart transplantation in children older than 1 year of age.3 Unlike adults, whose main cause is coronary heart disease, the aetiology in the paediatric population is Correspondence to: J. O. Miranda, Department of Paediatric Cardiology, Centro Hospitalar São João. Alameda Prof. Hernâni Monteiro, 4202–451 Porto, Portugal. Tel: + 351 225512100; Fax: + 351225512273; E-mail: [email protected]
mainly idiopathic or due to myocarditis, inherited metabolic diseases, neuromuscular diseases and malformative syndromes.2,4 The demographics and underlying causes of paediatric dilated cardiomyopathy are not well characterised, particularly in our country. A better understanding of the epidemiology, aetiology and outcome of the disease would facilitate planning and provision of medical services. The aim of the study was to provide a detailed description of clinical profile and outcome of dilated cardiomyopathy in children.
Methodology We performed a retrospective review of children diagnosed with dilated cardiomyopathy from January, 2005 to June, 2012 in a tertiary centre of Paediatric
334
February 2015
Cardiology in the Young
Clinical presentation The majority of the patients had clinical evidence of heart failure at diagnosis [n = 51 (83.6%)]. Of all, 44.3% (n = 27) needed to be admitted to an intensive care unit. The need for intensive care admission was significantly higher in younger patients (21.0 months versus 63.7 months, p = 0.009). Family history of dilated cardiomyopathy and sudden death were observed in two patients, each. A measured left ventricular ejection fraction at clinical presentation was available for 85.2% of patients; in the remaining patients, there was qualitative information of reduced left ventricular systolic function. The mean left ventricular ejection fraction was 32.0% (standard deviation ±13.0%). Left ventricular ejection fraction ⩽30% was observed in 23 patients (37.7%), between 30% and 50% in 24 patients (39.3%) and >50% in five patients (8.2%). Patients admitted to an intensive care unit had a significantly lower mean left ventricular ejection fraction at presentation (mean −8%, p = 0.026).
Cardiology. All patients were examined by a paediatric cardiologist and data reported were based on comprehensive chart review of each patient visit. Demographic data, clinical presentation, aetiology, treatment and outcome were assessed. The diagnostic criteria for dilated cardiomyopathy were (i) reduced left ventricular systolic function on any form of cardiac imaging in patients with symptoms or a family history of dilated cardiomyopathy, (ii) a measured left ventricular ejection fraction 2 years Ejection Fraction average (SD) Hospital admission [n (%)] Intensive care admission [n (%)]
Other (n = 12) Idiopathic [n = 29 Myocarditis [n = 11 Inherited metabolic Neuro-muscular diseases (47.5%)] (18.0%)] diseases [n = 7 (11.5%)] [n = 2 (3.3%)]
Outcome The overall mortality rate was 16.1% (n = 10) (Table 2). The median age at death was 6.5 years and median time interval from the diagnosis to death was about 7.5 months (IQR 60.8 months). The mortality was significantly higher in patients under 1 year of age (32.0% versus 5.6%, p = 0.006). Analysing the outcome by the composite endpoint of death and/or transplantation according to the aetiologies subgroups, the subgroup with a significantly better outcome was the myocarditis group, with no deaths or transplants registered (0% versus 30% in the remaining subgroups, p = 0.036). The aetiological subgroup with higher mortality and/or transplantation, although not statistically significant, was the idiopathic subgroup (16.4% versus 8.2% in the remaining subgroups, p = 0.079). Within inherited metabolic disease causes, only one patient died (Barth Syndrome patient) (Table 2). In all, five patients underwent heart transplantation: two of them in other centres and three of them in our centre – an idiopathic form, a familial form and a left ventricular non-compaction disease; the median age at transplantation was 11.7 years. After 2 years of follow-up, no mortality was observed in transplanted patients.
Table 2. Characteristics at diagnosis and outcome of 61 patients with Dilated cardiomyopathy (DCM), by aetiology.
Therapy At the time of dilated cardiomyopathy diagnosis, 82.0% (n = 50) of the patients were started on anticongestive medication, 80.3% (n = 49) received an angiotensin-converting enzyme inhibitor and 72.1% (n = 44) antiaggregant therapy. Antiarrhythmic agents and inotropes were used on 29.5% (n = 18) of cases, each. There was a lower use of β-blockers [n = 11 (18.0%)] and calcium channel blockers [n = 1 (1.6%)]. Pacemaker and ventricular assist device were rarely used [n = 2 (3.3%) and n = 1 (1.6%), respectively]. Ventricular assist device was used only in one patient, as a bridge to transplantation.
p-value*
Of all patients, 50.7% (n = 31) were evaluated at inherited metabolic diseases consultation. Inherited metabolic diseases identified were: three cases of mitochondrial citopathies – including one Barth Syndrome – two cases of fatty acid oxidation disease (long-chain acyl CoA dehydrogenase deficiency) and two cases of lysosomal storage diseases (Mucopolysaccharidosis type I and type VI). In the majority (n = 5/7), dilated cardiomyopathy presentation preceded the inherited metabolic disease diagnosis. Duchenne and Becker muscular dystrophy were the two neuromuscular diseases identified. The polymalformative syndrome associated with dilated cardiomyopathy was Jacobsen Syndrome.
Total (n = 61)
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336
Cardiology in the Young
Among not transplanted survivors, the median follow-up time from diagnosis of dilated cardiomyopathy was 35.5 months (IQR 51.3 months). Of those, 24.6% (n = 15) maintained cardiac dysfunction despite pharmacological therapy and 36.1% (n = 22) had normalisation of cardiac function.
Discussion Dilated cardiomyopathy is an important cause of heart failure in children and, although a variety of aetiological factors have been investigated, a significant proportion of our patients with documented dilated cardiomyopathy did not have a demonstrable cause. In fact, almost half of our patients had an idiopathic form of dilated cardiomyopathy. In the literature, an idiopathic form of dilated cardiomyopathy is usually reported in about two-thirds to a half of the children.1,4,7 Viral myocarditis is an important, and often unrecognised, cause of dilated cardiomyopathy. The exact incidence of myocarditis is difficult to ascertain as the viral evaluation by polymerase chain reaction, although performed in most clinically suggestive cases, was not performed in all patients. Despite that, a high prevalence of Parvovirus B19 was observed in our population. In fact, the epidemiology of viral myocarditis has been changing in the past few decades. After 1995, as the prevalence of enterovirus decreased, the prevalence of adenovirus increased.8,9 More recently, Parvovirus B19 is reported as the most commonly detected viral genome. Whereas the pathogenic role of enterovirus and adenovirus in myocarditis and dilated cardiomyopathy is well established, the role of Parvovirus B19 is uncertain. Whether it is an incidental or a pathogenic agent in acute myocarditis is still unclear.10–12 In our series, a significant proportion of cases caused by inherited metabolic diseases was identified, 11.5% of the cases when compared with the 4–6% described in the literature.4,13,14 This evidence is probably due to the high rate of metabolic diseases investigation. These data reinforce the importance of considering inherited metabolic diseases in the differential diagnosis of children presenting with dilated cardiomyopathy, as it is crucial to define prognosis. The ideal time to diagnose inherited metabolic diseases is obviously the neonatal period, before clinical manifestations, using newborn screening followed by confirmatory studies. However, as three of our patients had mitochondrial citopathies, not included in the neonatal screening, and long-chain acyl CoA dehydrogenase deficiency patients were born before the inclusion of the disease in the neonatal screening, the majority of our patients had identification of the
February 2015
metabolic disease in the aetiological study for dilated cardiomyopathy. Recent population data from several groups have improved our understanding about the natural history of dilated cardiomyopathy. The Paediatric Cardiomyopathy Registry in North America showed a 5-year survival rate of 54% for dilated cardiomyopathy.14 The National Australian Childhood Cardiomyopathy Study showed 5-year freedom from death or transplantation of 63% for children with dilated cardiomyopathy.7 The predictors of survival for dilated cardiomyopathy vary considerably between series. The most consistent risk factors at diagnosis for subsequent death or transplantation are age, congestive heart failure, lower fractional shortening and ejection fraction and aetiology of dilated cardiomyopathy.4,18,19 In our study, age at diagnosis and aetiology were the most important prognosis factors. We observed that younger patients had worse prognosis: the younger the patient the greater the need for intensive care (p = 0.009) and, additionally, patients under 1 year of age presented higher mortality (p = 0.006). Aetiology also presented as an important prognostic factor. In fact, it is essential to establish the aetiology of dilated cardiomyopathy to determine the subsequent optimal management and more accurate prognosis. The idiopathic forms of dilated cardiomyopathy have a significant impact on morbidity and mortality in paediatric population. The overall prognosis of idiopathic forms tends to be poor, with a reported 5-year mortality rate in the literature of about 14–50%, from either sudden cardiac death or pump failure.1,7,15,16 In our population, the mortality rate of this specific subgroup was of 24%, thus superior to overall mortality of 16.1%. The worse prognosis associated with idiopathic forms, in comparison to other causes of dilated cardiomyopathy, raises questions about its optimal management: should these patients go through a more exhaustive aetiological study or should they undergo heart transplantation sooner? On the other hand, the outcome of viral myocarditis in children is superior. Studies have shown survival rates of between 75% and 100% for acute myocarditis in childhood.17 In our patients, viral myocarditis resulted in no mortality or transplantation. This emphasises the benefit of knowing the diagnosis of myocarditis, as acute transplantation should be avoided, even if mechanical support is required. This will provide the opportunity for cardiac recovery, as well as minimise the risks of transplantation during recent or active viral infection.18 With regard to treatment, anticongestive agents, angiotensin-converting enzyme inhibitors and antiaggregant therapy were the most commonly used drugs.
Vol. 25, No. 2
Miranda et al: Paediatric dilated cardiomyopathy
Pacemaker and ventricular assist device were rarely used. When acute heart failure is unresponsive to aggressive medical management, institution of mechanical circulatory support must be considered, sometimes as a bridge to transplantation. Heart transplantation remains the main therapy for end-stage heart failure refractory to surgical and medical therapy in children. In the literature, current 1-year survival after heart transplantation in children is 85%; the overall survival rate 20 years after transplantation is 40%.20 With a modest experience in paediatric heart transplantation, we report no mortality in patients who underwent transplantation, after 2 years of follow-up. The present report reflects the reality of the referral network of our tertiary centre, representing an overview of paediatric dilated cardiomyopathy. The observational and retrospective nature of the study constitutes a limitation. The centralisation of paediatric tertiary services provides a great opportunity to examine the presentation and natural history of this rare condition. A comprehensive analysis of data obtained from different observational studies can expand our understanding about the natural history of dilated cardiomyopathy in the paediatric population.
Acknowledgements None.
Financial Support This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
3.
4.
5.
6. 7.
8.
9.
10.
11.
12.
13.
14.
Conflicts of Interest 15.
None.
References 1. Lipshultz SE, Sleeper LA, Towbin JA, et al. The incidence of paediatric cardiomyopathy in two regions of the United States. N Engl J Med 2003; 348: 1647–1655. 2. Maron BJ, Towbin JA, Thiene G, et al. American Heart Association Council on Clinical Cardiology, Heart Failure and Transplantation, Council on Clinical Cardiology, Heart Failure and Transplantation Committee, Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups, and Council on Epidemiology and Prevention. Contemporary definitions and classifications of the cardiomyopathies: an American Heart Association scientific statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee;
16.
17. 18.
19.
20.
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