Pediatric Restrictive Cardiomyopathy
- Author: Kimberly Y Lin, MD; Chief Editor: Stuart Berger, MD more...
Background
Restrictive cardiomyopathy (RCM) is a rare disorder in children that is characterized by restrictive filling and reduced diastolic volume of one or both ventricles with normal or near-normal systolic function and wall thickness.[1] The heart is structurally normal, although histologic abnormalities are often present, depending on the etiology of the restrictive cardiomyopathy.
RCM may manifest as a solitary abnormality, although restrictive filling patterns of the left ventricle can be seen in patients with dilated or hypertrophic cardiomyopathy. Because this disease is so rare, its pathogenesis, natural history, and treatment are not well defined. Associated syndromes and noncardiac conditions include scleroderma, amyloidosis, sarcoidosis, Gaucher disease, Hurler disease, glycogen storage diseases, hypereosinophilic syndrome, and carcinoid syndrome.
Some investigators have divided RCM into the following subtypes: (1) pure restrictive cardiomyopathy, (2) hypertrophic-restrictive cardiomyopathy, and (3) mildly dilated restrictive cardiomyopathy.[2]
Therapy for idiopathic restrictive cardiomyopathy (RCM) is limited to symptomatic treatment and is often ineffective in improving outcome. Surgical options are limited to heart transplantation. A healthy lifestyle is recommended, although there is an increased risk of sudden death and worsening heart failure, which generally precludes competitive sports participation.
Pathophysiology
The pathophysiology of RCM is diverse. This condition can be associated with diseases such as amyloidosis, hemosiderosis, hypereosinophilia, and endocardial fibroelastosis; it can also occur secondary to radiation therapy and certain medications. However, these may be considered separate diseases because the etiology is known.
In true idiopathic RCM, endomyocardial biopsy and pathologic specimen findings are usually abnormal, although they may not be diagnostic for any single disease. Findings include myofibrillar disarray, myocyte hypertrophy, and interstitial fibrosis. Morphologic findings include atrial enlargement without increased ventricular wall thickness or ventricular cavity dilation, the absence of eosinophilic infiltration, and the absence of pericardial disease.[2, 3]
The physiologic consequences of RCM are more uniform than those of its diverse etiologies. Typically, there is abrupt premature cessation of ventricular filling in early diastole, causing a dip-and-plateau or square-root pattern on ventricular pressure tracings. Therefore, ventricular filling is limited to early diastole. This ultimately results in decreased compliance of the ventricle with development of atrial dilation. Typical hemodynamic characteristics include normal systolic function and equalization of increased ventricular end-diastolic pressures.
The natural history of RCM varies and is at least partially dependent on the etiology, if any is identified. Because the number of patients that have subclinical RCM is unknown, the natural history can be determined only when symptoms develop. Once symptoms develop, the morbidity and mortality are high (see Prognosis and Complications).
Etiology
In most pediatric cases of RCM, the etiology is unknown. Risk factors are also unknown.
RCM can be divided into 2 main types, myocardial and endomyocardial. The myocardial type, in turn, can be further classified into 2 subtypes, noninfiltrative and infiltrative.
Noninfiltrative myocardial forms of RCM include the following:
- Idiopathic (the most common etiology of RCM in children)
- Familial
- Post–cardiac transplant
- Diabetic cardiomyopathy with a restrictive component
Infiltrative myocardial causes of RCM include the following:
- Amyloidosis (the most common cause of RCM in adults outside of the tropics)[4]
- Hemochromatosis
- Lysosomal storage diseases such as Gaucher disease, Hurler disease, and Fabry disease
Endomyocardial causes of RCM include the following:
- Endomyocardial fibrosis (EMF; the most common cause of restrictive cardiomyopathy in adults and children in certain tropical areas of Africa, Asia, and South America)[5]
- Hypereosinophilic syndrome (also known as Loeffler endocarditis)
- Carcinoid heart disease
- Metastatic cancers
- Pseudoxanthoma elasticum
- Certain drugs, including anthracyclines and methysergide
- Mediastinal radiation
Most cases of RCM (including idiopathic ones) are not known to be inherited, although there have been reports of families in whom multiple members are affected by a combination of hypertrophic and restrictive cardiomyopathies. Additionally, some inherited infiltrative disorders can cause restrictive cardiomyopathy. These include Fabry disease (X-linked recessive), Gaucher disease (autosomal recessive), glycogen storage diseases, and autosomal recessive hemochromatosis.
Significant progress has been made in defining the genetic causes of RCM. These causes include mutations in the following genes: troponin I, troponin T, alpha-cardiac actin, myosin, and desmin.[6, 7, 8, 9, 10, 11, 12] Genetic mutations have also been identified in several diseases associated with RCM, including lamin A/C in Emery-Dreifuss muscular dystrophy, transthyretin in amyloidosis, and RSK2 in Coffin-Lowry syndrome.[13, 14, 15]
Epidemiology
Although its exact prevalence is unknown, RCM is the least common cardiomyopathy and represents approximately 2-5% of pediatric cardiomyopathies in the United States.[16, 17, 18] Reports from Europe and Australia suggest similar international infrequency.[19, 20] However, in tropical areas of Africa, Asia, and South America where endomyocardial fibrosis is endemic, the prevalence may be much higher.[21, 22]
Idiopathic RCM has been described in children of all ages. Some studies suggest that idiopathic RCM may be slightly more common in girls than in boys.[23, 24] No racial predilection is known.
Prognosis
The prognosis of RCM can be very poor in children. Patients are at risk for various acute and chronic complications that require close monitoring. Those who ultimately require and undergo heart transplantation before development of severe, irreversible pulmonary hypertension have a reasonably good prognosis after transplantation, comparable to those with other types of cardiomyopathy.
Mortality in children with idiopathic RCM is high, particularly in the absence of heart transplantation. Rates have been reported to be as high as 63% within 3 years of diagnosis and 75% within 6 years of diagnosis.[16] Actuarial survival range is 44-50% at 1-2 years after presentation.[16, 24] This decreases to 29-39% at 3-5 years after presentation.[18, 24]
Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O'Connell J. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation. Mar 1 1996;93(5):841-2. [Medline].
Angelini A, Calzolari V, Thiene G, et al. Morphologic spectrum of primary restrictive cardiomyopathy. Am J Cardiol. Oct 15 1997;80(8):1046-50. [Medline].
Hirota Y, Shimizu G, Kita Y, et al. Spectrum of restrictive cardiomyopathy: report of the national survey in Japan. Am Heart J. Jul 1990;120(1):188-94. [Medline].
Kushwaha SS, Fallon JT, Fuster V. Restrictive cardiomyopathy. N Engl J Med. Jan 23 1997;336(4):267-76. [Medline].
Mocumbi AO, Yacoub S, Yacoub MH. Neglected tropical cardiomyopathies: II. Endomyocardial fibrosis: myocardial disease. Heart. Mar 2008;94(3):384-90. [Medline].
Peddy SB, Vricella LA, Crosson JE, et al. Infantile restrictive cardiomyopathy resulting from a mutation in the cardiac troponin T gene. Pediatrics. May 2006;117(5):1830-3. [Medline].
Mogensen J, Kubo T, Duque M, et al. Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J Clin Invest. Jan 2003;111(2):209-16. [Medline].
Kaski JP, Syrris P, Burch M, et al. Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes. Heart. Nov 2008;94(11):1478-84. [Medline].
Ware SM, Quinn ME, Ballard ET, Miller E, Uzark K, Spicer RL. Pediatric restrictive cardiomyopathy associated with a mutation in beta-myosin heavy chain. Clin Genet. Feb 2008;73(2):165-70. [Medline].
Goldfarb LG, Park KY, Cervenakova L, et al. Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat Genet. Aug 1998;19(4):402-3. [Medline].
Pruszczyk P, Kostera-Pruszczyk A, Shatunov A, et al. Restrictive cardiomyopathy with atrioventricular conduction block resulting from a desmin mutation. Int J Cardiol. Apr 25 2007;117(2):244-53. [Medline].
Dalakas MC, Park KY, Semino-Mora C, et al. Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N Engl J Med. Mar 16 2000;342(11):770-80. [Medline].
Sanna T, Dello Russo A, Toniolo D, et al. Cardiac features of Emery-Dreifuss muscular dystrophy caused by lamin A/C gene mutations. Eur Heart J. Dec 2003;24(24):2227-36. [Medline].
Imamura T, Nakazato M, Date Y, et al. Cardiac amyloidosis associated with a novel transthyretin aspartic acid-18 glutamic acid de novo mutation. Circ J. Nov 2003;67(11):965-8. [Medline].
Facher JJ, Regier EJ, Jacobs GH, et al. Cardiomyopathy in Coffin-Lowry syndrome. Am J Med Genet A. Jul 15 2004;128(2):176-8. [Medline].
Denfield SW, Rosenthal G, Gajarski RJ, et al. Restrictive cardiomyopathies in childhood. Etiologies and natural history. Tex Heart Inst J. 1997;24(1):38-44. [Medline].
Lipshultz SE, Sleeper LA, Towbin JA, et al. The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med. Apr 24 2003;348(17):1647-55. [Medline].
Russo LM, Webber SA. Idiopathic restrictive cardiomyopathy in children. Heart. Sep 2005;91(9):1199-202. [Medline]. [Full Text].
Nugent AW, Daubeney PE, Chondros P, et al. The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med. Apr 24 2003;348(17):1639-46. [Medline].
Malcic I, Jelusic M, Kniewald H, Barisic N, Jelasic D, Bozikov J. Epidemiology of cardiomyopathies in children and adolescents: a retrospective study over the last 10 years. Cardiol Young. May 2002;12(3):253-9. [Medline].
Bukhman G, Ziegler J, Parry E. Endomyocardial fibrosis: still a mystery after 60 years. PLoS Negl Trop Dis. 2008;2(2):e97. [Medline].
Mocumbi AO, Ferreira MB, Sidi D, Yacoub MH. A population study of endomyocardial fibrosis in a rural area of Mozambique. N Engl J Med. Jul 3 2008;359(1):43-9. [Medline].
Cetta F, O'Leary PW, Seward JB, Driscoll DJ. Idiopathic restrictive cardiomyopathy in childhood: diagnostic features and clinical course. Mayo Clin Proc. Jul 1995;70(7):634-40. [Medline].
Lewis AB. Clinical profile and outcome of restrictive cardiomyopathy in children. Am Heart J. Jun 1992;123(6):1589-93. [Medline].
Arbustini E, Pasotti M, Pilotto A, Pellegrini C, Grasso M, Previtali S. Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects. Eur J Heart Fail. Aug 2006;8(5):477-83. [Medline].
Vaitkus PT, Kussmaul WG. Constrictive pericarditis versus restrictive cardiomyopathy: a reappraisal and update of diagnostic criteria. Am Heart J. Nov 1991;122(5):1431-41. [Medline].
Choi EY, Ha JW, Kim JM, et al. Incremental value of combining systolic mitral annular velocity and time difference between mitral inflow and diastolic mitral annular velocity to early diastolic annular velocity for differentiating constrictive pericarditis from restrictive cardiomyopathy. J Am Soc Echocardiogr. Jun 2007;20(6):738-43. [Medline].
Friedberg MK, Silverman NH. The systolic to diastolic duration ratio in children with heart failure secondary to restrictive cardiomyopathy. J Am Soc Echocardiogr. Nov 2006;19(11):1326-31. [Medline].
Hatle LK, Appleton CP, Popp RL. Differentiation of constrictive pericarditis and restrictive cardiomyopathy by Doppler echocardiography. Circulation. Feb 1989;79(2):357-70. [Medline].
Rivenes SM, Kearney DL, Smith EO, Towbin JA, Denfield SW. Sudden death and cardiovascular collapse in children with restrictive cardiomyopathy. Circulation. Aug 22 2000;102(8):876-82. [Medline]. [Full Text].
Talreja DR, Nishimura RA, Oh JK, Holmes DR. Constrictive pericarditis in the modern era: novel criteria for diagnosis in the cardiac catheterization laboratory. J Am Coll Cardiol. Jan 22 2008;51(3):315-9. [Medline].
Yoshizato T, Edwards WD, Alboliras ET, et al. Safety and utility of endomyocardial biopsy in infants, children and adolescents: a review of 66 procedures in 53 patients. J Am Coll Cardiol. Feb 1990;15(2):436-42. [Medline].
[Guideline] Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation. Nov 6 2007;116(19):2216-33. [Medline].
Maron BJ, Ackerman MJ, Nishimura RA, Pyeritz RE, Towbin JA, Udelson JE. Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol. Apr 19 2005;45(8):1340-5. [Medline].
Weller RJ, Weintraub R, Addonizio LJ, et al. Outcome of idiopathic restrictive cardiomyopathy in children. Am J Cardiol. Sep 1 2002;90(5):501-6. [Medline].
Bengur AR, Beekman RH, Rocchini AP. Acute hemodynamic effects of captopril in children with a congestive or restrictive cardiomyopathy. Circulation. Feb 1991;83(2):523-7. [Medline].
Shaddy RE. Pulmonary hypertension in pediatric heart transplantation. Prog Pediatr Cardiol. Jun 1 2000;11(2):131-136. [Medline].
Towbin JA. Cardiomyopathy and heart transplantation in children. Curr Opin Cardiol. May 2002;17(3):274-9. [Medline].
Fenton MJ, Chubb H, McMahon AM, et al. Heart and heart-lung transplantation for idiopathic restrictive cardiomyopathy in children. Heart. Jan 2006;92(1):85-9. [Medline].
Kimberling MT, Balzer DT, Hirsch R, Mendeloff E, Huddleston CB, Canter CE. Cardiac transplantation for pediatric restrictive cardiomyopathy: presentation, evaluation, and short-term outcome. J Heart Lung Transplant. Apr 2002;21(4):455-9. [Medline].
Bograd AJ, Mital S, Schwarzenberger JC, Mosca RS, Quaegebeur JM, Addonizio LJ. Twenty-year experience with heart transplantation for infants and children with restrictive cardiomyopathy: 1986-2006. Am J Transplant. Jan 2008;8(1):201-7. [Medline].
Al-Khaldi A, Reitz BA, Zhu H, Rosenthal D. Heterotopic heart transplant combined with postoperative Sildenafil use for the treatment of restrictive cardiomyopathy. Ann Thorac Surg. Apr 2006;81(4):1505-7. [Medline].
Print
