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Clinical features of isolated left ventricular noncompaction in children
International Journal of Cardiology 97 (2004) 233 – 237 www.elsevier.com/locate/ijcard
Clinical features of isolated left ventricular noncompaction in children Dursun Alehan * Division of Pediatric Cardiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey Received 4 April 2003; received in revised form 27 August 2003; accepted 8 September 2003
Abstract Background: Ventricular noncompaction is a rare unclassified cardiomyopathy due to intrauterin arrest of compaction of the loose interwoven meshwork with limited data regarding diagnosis and outcome in children. Methods: In this study we describe clinical features of isolated left ventricular noncompaction (IVNC) in children and compare our findings with those previously reported. A diagnosis of ventricular noncompaction was made according to the characteristic echocardiographic appearance of two-layered myocardial wall consisting of a thin compacted epicardial and a thick noncompacted endocardial layer with numerous, prominent trabeculations and deep intertrabecular recesses communicating with left ventricular cavity. Results: Nine children, eight male and one female, with ages ranging from 10 days to 12 years and follow-up as long as 5 years were included into the study. The primary diagnosis of IVNC had been missed in four of the patients. Clinical manifestations were heart failure in five patients, cardiac murmur in two, dizziness in one, and palpitation in one patient. All patients, except two asymptomatic ones, had electrocardiographic abnormalities. Four patients required hospital admission for decompansated heart failure. Two patients died during follow-up while waiting for heart transplantation. Familial occurrence, ventricular tachycardia and thromboembolic events were not observed in any of the patients. Conclusions: Although IVNC is present at birth, it may become clinically overt at any time from infancy through adolescence. Physicians and echocardiographers should be familiar with the diagnostic pattern of ventricular noncompaction in order to prevent any delay in diagnosis. Since associated morbidity and mortality rates are high, these patients require regular follow-up. D 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Isolated ventricular noncompaction; Cardiomyopathy; Children; Echocardiography
1. Introduction Noncompaction of the ventricular myocardium is a rare congenital disorder categorized as unclassified cardiomyopathy by the World Health Organization [1]. It is believed to be due to an arrest in the normal endomyocardial embryogenesis, and may occur in isolation or may be associated with other congenital heart anomalies [2]. Characteristic echocardiographic findings consist of multiple, prominent myocardial trabeculations and deep intertrabecular recesses communicating with the ventricular cavity [3– 5]. Despite an increasing awareness and interest in this anomaly, knowledge regarding diagnosis and long-term prognosis in children is still limited. In this report, which represents the second largest pediatric population to date, we describe nine children with
* Sinan Caddesi, No. 115/4 Dikmen, 06450 Ankara, Turkey. Tel.: +90312-3104258; fax: +90-312-3090220. E-mail address: [email protected] (D. Alehan). 0167-5273/$ - see front matter D 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2003.09.004
isolated left ventricular noncompaction (IVNC) and compare our results with those of previous reports.
2. Methods The study group consisted of nine patients (eight males and one female) with ages ranging from 10 days to 12 years, seen in our department during a 4-year period ending in December 2002. The data included personal and family history, physical examination, 12-lead electrocardiogram (ECG), chest X-ray, two-dimensional echocardiogram with Doppler interrogation, and 24-h Holter recording. Additionally, patients 6 and 7 had intracardiac electrophysiological studies. Echocardiographic examination was performed in all patients according to the recommendations of the American Society of Echocardiography including two-dimensional guided M-mode measurements [6,7]. Distribution of prominent trabeculations in the ventricles was assessed using parasternal, apical, and subxiphoid imaging planes.
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Echocardiopraphic data also included ventricular enddiastolic and end-systolic dimensions, fractional shortening, and ejection fraction. A diagnosis of isolated ventricular noncompaction was made according to the characteristic echocardiographic appearance of a twolayered structure of the myocardial wall consisting of a thin compacted epicardial layer and a thick noncompacted endocardial layer (ratio of noncompacted to compacted layers >2) with numerous, excessively prominent trabeculations and deep intertrabecular recesses communicating with the ventricular cavity [3– 5]. Echocardiograms were reviewed independetely by two pediatric cardiologists with expertise in echocardiography. Patients with coexisting cardiac abnormalities were excluded from the study.
3. Results 3.1. Clinical and electrocardiographic findings Clinical and electrocardiographic (ECG) characteristics of the patients are given in Table 1. Five patients presented with signs or symptoms of heart failure due to depressed left ventricular function. Two patients had no cardiac symptoms but was referred for evaluation of cardiac murmur. One patient presented with palpitation and dyspnea and one with dizziness. Familial occurrence or dysmorphic facial appearance were not observed in any of the patients. Patient 5 was the only patient with associated noncardiac malformations, and had esophageal atresia and tracheoesophageal fistula. Seven patients showed abnormalities on baseline ECG including left ventricular hypertrophy (based on voltage and repolarization criteria) and ST depression with flat or negative T waves in leads II, III, aVF and V4 – V6, prema-
Table 2 Echocardiographic findings of the patients at presentationa Case LVEDD (mm)
LFESD (mm)
EF SF Localization of (n: >55%) (n: 29 – 48%) noncompacted segments
1 2
35 (n: < 24) 30 (n: < 18) 29% 56 (n: < 40) 43 (n: < 27) 46%
13% 23%
3
55 (n: < 42) 40 (n: < 28) 46%
23%
4
47 (n: < 36) 41 (n: < 24) 26%
12%
5
20 (n: < 24) 12 (n: < 18) 68%
35%
6
62 (n: < 42) 55 (n: < 22) 24%
11%
7
43 (n: < 43) 27 (n: < 28) 68%
37%
8
54 (n: < 47) 41 (n: < 32) 48%
24%
9
18 (n: < 24) 12 (n: < 18) 69%
35%
LV apex LV apex, LW LV apex, LW LV apex, LW LV apex, LW LV apex, LW LV apex, LW LV apex, LW LV apex,
PW, PW, PW, PW, PW, PW, PW, PW
EF = ejection fraction; LV = left ventricle; LVEDD = left ventricle enddiastolic diameter; lVESD = left ventricle end-systolic diameter; LW = lateral wall; mm = millimeter; n = normal; PW = posterior wall; SF = shortening fraction. a Normal LV dimensions for children were obtained from Ref. [8].
ture ventricular contractions, and sinus bradycardia. Patients 5 and 9 were the only ones with a normal ECG. 3.2. Echocardiographic examinations Echocardiographic findings are summarized in Table 2. Two-dimensional echocardiograms showed numerous prominent trabeculations and deep intertrabecular recesses communicating with the ventricle in all nine patients (Figs. 1 and 2). Noncompacted myocardial segments were predominantly localized to the ventricular apex and posterior wall. Left ventricle was markedly dilated and left ventricular systolic function was severely depressed in six patients,
Table 1 Patient characteristics Case
Age at presentation
Weight (kg)
Gender
Clinical presentation
ECG
Associated findings
Follow-up (years)
Outcome
1 2
1,5 months 9 years
4.5 22
M M
Heart failure Heart failure
0 0
2 5
3 4 5
11 years 5 years 10 days
28 15.5 3
M M M
Heart failure Heart failure Murmur
LVH, ST-T wave changes LVH, ST-T wave changes Mobitz type II A-V block LVH, ST-T wave changes LVH, ST-T wave changes Normal
0 0 EA, TEF
3 3 1
6
7 years
24
M
LVH, ST-T wave changes PVC
0
5
7 8 9
12 years 12 years 1 month
30 45 4
M M F
Dispnea, palpitation Dizziness Heart failure Murmur
Died Pacemaker implantation, Died DSF DSF Surgery for EA and TEF, NSF DSF
Sinus bradycardia LVH, ST-T wave changes Normal
0 0 0
1 2.5 0.6
NSF DSF NSF
A-V = atrioventricular; CHD = congenital heart disease; DSF = decreased systolic function; EA = esophageal atresia; F = female; LVH = left vetricular hypertrophy; M = male; NSF = normal systolic function; PVC = premature ventricular contraction; TEF = tracheoesophageal fistula.
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whereas ventricle size and function were normal in three patients [8]. Intracardiac thrombus was not detected in any of the patients by echocardiography. The initial diagnosis of IVNC had been missed in four of our cases (patients 1, 2, 3 and 6). Delay in the diagnosis of IVNC was due to similarities between IVNC and other cardiomyopathies and to the examiner’s unfamilarity with its specific diagnostic pattern. Incorrect diagnosis was dilated cardiomyopathy in all of the patients. 3.3. Follow-up Mean duration of follow-up was 30.3 months (range: 6 –60 months). Hospital admission for severe heart failure was required in four patients. During follow-up, patient 2 developed Mobitz type II second-degree atrioventricular block with severe bradycardia and required permanent pacemaker implantation. He was hospitalized twice and died due to progressive ventricular dysfunction, 5 years after the initial diagnosis while waiting for heart transplantation. Patient 1 also died 2 years after the diagnosis because of severe heart failure. Patients 3, 4, 6 and 8 continued to have decreased systolic function and have been treated with digoxin, diuretics, and angiotensin-converting enzyme inhibitors. Additionally, they were given aspirin in an attempt to prevent thromboembolic events. Patient 5 underwent surgery for esophageal atresia and tracheoesophageal fistula. He and patient 9 had shown no symptoms related to cardiovascular system and had required no medication during the short follow-up period. Patient 7 had resting heart rates of < 50 beats/min and premature ventricular contractions (PVC) occurred during exercise testing in this patient. However, ventricular tachycardia was inducible neither in this patient nor in patient 5
Fig. 1. A representative two-dimensional echocardiogram in a patient with isolated ventricular noncompaction (patient 3). Parasternal long-axis view demonstrates a thin epicardial layer and an extremely thickened endocardial layer with prominent trabeculations and deep recesses in the apex and posterior wall of the left ventricle. LA: left atrium; LV: left ventricle.
Fig. 2. Modified parasternal long-axis view of patient 1. Two dimensional echocardiogram shows prominent trabeculations and deep recesses (arrows) in the apex of the left ventricle. LV: left ventricle.
(with PVC’s on surface ECG) during intracardiac electrophysiological study. Clinically overt thromboembolic events or ventricular tachycardia were not observed in any of the patients.
4. Discussion Isolated ventricular noncompaction is a rare cardiomyopathy with limited data regarding diagnosis and outcome in children. While echocardiography, magnetic resonance imaging, computed tomography, and angiography are all reliable imaging modalities to diagnose ventricular noncompaction, two-dimensional echocardiography with color and Doppler studies is the standard and first-line diagnostic tool [2,4,9 – 11]. However, for the correct diagnosis, the echocardiographer should be familiar with this congenital disorder and clear cut diagnostic criteria should be used. Despite an increasing awareness in this anomaly, there is still little knowledge regarding diagnosis of this rare cardiomyopathy. Indeed, the primary diagnosis of IVNC had been missed in four of our patients. The delay in diagnosis was due to the similarities between IVNC and other cardiomyopathies, and to the unfamilarity of the referring physicians with its specific diagnostic pattern. The incorrect diagnoses had been dilated cardiomyopathy in all of the patients. Other misdiagnoses reported in the literature include hypertrophic cardiomyopathy, restrictive cardiomyopthy, endocardial fibroelastosis and myocarditis [12,13]. Similar to our findings, Ichida et al. [13] also pointed out that the diagnosis of IVNC had been missed and several echocardiographic examinations had been required to diagnose IVNC in the majority of their cases. Left ventricular trabeculations have also been reported in 68% of normal hearts [14]. Thus the differentiation between variants and IVNC may be challenging in some
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cases. The characteristic discriminating feature to diagnose IVNC is the two-layered myocardial wall structure with both a thin epicardial compacted zone and an extremely thickened endocardial noncompacted zone with numerous and prominent trabeculations and deep recesses filled with blood from the ventricular cavity [3,5]. In the presence of these findings, a maximal end systolic ratio of noncompacted to compacted layers of >2 is diagnostic [3,5]. This rare abnormality is reported to be accompanied by three major risks, namely depressed ventricular function, endocardial clot with systemic embolization and ventricular arrhythmias that may be sometimes fatal [2]. The cause of depressed ventricular function is not clear. The coronary arteries are normal in these patients. However, recently restricted myocardial perfusion and decreased coronary flow reserve, suggestive of coronary microcirculatory dysfunction, were demonstrated by positron emission tomography in patients with IVNC [9,16]. Decreased coronary flow reserve was not only confined to noncompacted segments, but extended to most segments with wall motion abnormalities [16]. This finding suggests that coronary microcirculatory dysfunction may play a role in the development of impaired ventricular function [9,16]. Due to depressed ventricular function these patients usually present with heart failure similar to that of dilated cardiomyopathy. This was seen in six of our patients, in whom systolic function of the noncompacted myocardium was severely depressed. The patients described by Chin et al. [2] also manifested severe heart failure, ventricular tachycardia or embolic events at initial presentation and experienced a rapidly progressive clinical course. However, the current study differs from Chin’s study by absence of embolic events and ventricular tachycardia in Turkish children despite severely depressed ventricular functions. Our finding of no thromboembolic events may be due to small number of patient group or short follow-up period. Also the thromboembolic risk per se may be different in children from that in adults. Long-term studies with larger patient group may probably clarify the true thromboembolic risk in children. Ichida et al. [13] also reported many asymptomatic patients identified through mass screening who have longer clinical course with gradually depressed left ventricular function and restrictive hemodynamics. Their study is also characterized by absent systemic embolic events and very rare ventricular tachycardia in Japanese children. Our data and those of largest pediatric and adult series published so far are summarized in Table 3. Besides clinical features, the age range at diagnosis or onset of heart failure also varied widely in our study population as in previous studies [15]. Three of our patients, including one with heart failure, were diagnosed during neonatal period or early infancy whereas the others were asymptomatic until childhood. Thus, although IVNC is a congenital disorder and present at birth, its presentation may become clinically overt at any time from early infancy through adolescence.
Table 3 Characteristics of IVNC in the pediatric and adult population
Number of patients Age at diagnosis (median) Men Follow-up Facial dysmorphism Wolf – Parkinson – White syndrome Familial occurrence Heart failure symptom Systemic embolic events Deaths
Chin et al. [2]
Ichida et al. [13]
Present study
Oechslin et al. [3]
8 7 years
27 5 years
9 7 years
34 40 years
63% Up to 5 years 38% 13%
56% Up to 17 years 33% 15%
88% Up to 5 years 0% 0%
74% Up to 11 years 0% 0%
50% 63% 38% 38%
44% 30% 0% 7%
0% 56% 0% 22%
18% 68% 21% 35%
It is worth emphasizing that except two asymptomatic patients, all of our patients had an abnormal ECG at the time of presentation. In addition to baseline ECG abnormalities, patient 2 developed second-degree atrioventricular block requiring pacemaker implantation during follow-up. This suggests that ventricular conduction abnormalities may develop later in life and could be due to progressive endocardial fibrosis in association with IVNC [12,17]. Therefore regular follow-up is required for these patients. Our study revealed some features dissimilar to those previously reported in children. Although familial recurrences, facial dysmorphism and Wolff – Parkinson – White (WPW) syndrome were reported respectively in up to 50%, 38% and 15% of pediatric patients, they were absent in our patients [2,13,18,19]. Facial dysmorphism and WPW sydrome were also absent in a large adult population [3]. This clinical heterogeneity may be the result of different genetic background or genetic heterogeneity of this disorder, despite the same morphologic appearance of the cardiac anomaly [20,21]. Another interesting finding of the present study is the presence of esophageal atresia and tracheoesophageal fistula in one of our patients. Although IVNC may be associated with other noncardiac congenital malformations or syndromes, to our knowledge, this is the first association of this entity with esophageal atresia and tracheoesophageal fistula [22,23]. 4.1. Study limitations Our study population mostly consisted of patients referred to a tertiary care center because of heart failure. Therefore, there may be selection bias in this population representing mainly symptomatic patients. Also our study group is relatively small due to rare occurrence of IVNC. In conclusion, noncompaction of the ventricular myocardium is a rare congenital cardiomyopathy that may manifest itself from early infancy through adulthood with a wide clinical spectrum. Echocardiographers should be familiar
D. Alehan / International Journal of Cardiology 97 (2004) 233–237
with the diagnostic pattern of noncompaction in order to prevent any delay in diagnosis. Since associated morbidity and mortality rates are high, these patients require regular follow-up. As physicians become more aware of this rare disorder, the true prevalence and long-term prognosis of IVNC in an unselected group consisting of both asymptomatic and symptomatic patients will be better elucidated.
References [1] Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on definition and classification of cardiomyopathies. Circulation 1996;93:841 – 2. [2] Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R. Isolated noncompaction of left ventricular myocardium. A study of eight cases. Circulation 1990;82:507 – 13. [3] Oechslin EN, Attenhofer CH, Rojas JR, Kaufmann PA, Jenni R. Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol 2000;36:493 – 500. [4] Ritter M, Oechslin E, Sutsch G, Attenhofer C, Schneider J, Renni R. Isolated noncompaction of the myocardium in adults. Mayo Clin Proc 1997;72:26 – 31. [5] Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart 2001;86:666 – 71. [6] Sahn DJ, DcMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072 – 83. [7] American Society of Echocardiography Committee on Standards. Subcommittee on quantitation of two-dimensional echocardiograms. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr 1989;2:358 – 67. [8] Feigenbaum H. Echocardiographic measurements and normal values. In: Feigenbaum H, editor. Echocardiography. Philadelphia: Lea and Febiger; 1994. p. 658 – 83. [9] Junga G, Kneifel S, Von Smekal A, Steinert H, Bauersfeld U. Myocardial ischaemia in children with isolated ventricular non-compaction. Eur Heart J 1999;20:910 – 6.
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[10] Conces DJ, Ryan T, Tarver RD. Noncompaction of ventricular myocardium: CT appearance. Am J Roentgenol 1991;156:717 – 8. [11] Hamamichi Y, Ichida F, Hashimoto I, et al. Isolated noncompaction of the ventricular myocardium: ultrafast computed tomography and magnetic resonance imaging. Int J Card Imaging 2001;17:305 – 14. [12] Elshershari H, Okutan V, Cßeliker A. Isolated noncompaction of ventricular myocardium. Cardiol Young 2001;11:472 – 5. [13] Ichida F, Hamamichi Y, Miyawaki T, et al. Clinical features of isolated noncompaction of the ventricular myocardium. Long-term clinical course, hemodynamic properties, and genetic background. J Am Coll Cardiol 1999;34:233 – 40. [14] Boyd MT, Seward JB, Tajik AJ, Edwards WD. Frequency and location of prominent left ventricular trabeculations at autopsy in 474 normal human hearts: implications for evaluation of mural thrombi by two-dimensional echocardiography. J Am Coll Cardiol 1987; 9:323 – 6. [15] Neudorf UE, Hussein A, Trowitzsch E, Schmaltz AA. Clinical features of isolated noncompaction of the myocardium in children. Cardiol Young 2001;11:439 – 42. [16] Jenni R, Wyss CA, Oechslin EN, Kaufmann PA. Isolated ventricular noncompaction is associated with coronary microcirculatory dysfunction. J Am Coll Cardiol 2002;39:450 – 4. [17] Robida A, Hajar HA. Ventricular conduction defect in isolated noncompaction of the ventricular myocardium. Pediatr Cardiol 1996; 17:189 – 91. [18] Kurosaki K, Ikeda U, Hojo Y, Fujikawa H, Karsuki T, Shimada K. Familial isolated noncompaction of the left ventricular myocardium. Cardiology 1999;91:69 – 72. [19] Matsuda M, Tsukahara M, Kondoh O, Mito H. Familial isolated noncompaction of ventricular myocardium. J Hum Genet 1999;44:126 – 8. [20] Digilio MC, Marino B, Bevilacqua M, Musolino AM, Giannotti A, Dallapiccola B. Genetic heterogeneity of isolated noncompaction of the left ventricular myocardium. Am J Med Genet 1997;31:257 – 65. [21] Ichida F, Tsubata S, Bowles KR, et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation 2001;103:1256 – 63. [22] Wong JA, Bofinger MK. Noncompaction of the ventricular myocardium in Melnick – Needlees syndrome. Am J Med Genet 1997;71: 72 – 5. [23] Mandel K, Grunebaum E, Benson L. Noncompaction of the myocardium associated with Roifman syndrome. Cardiol Young 2001; 11:240 – 3.
Clinical features of isolated left ventricular noncompaction in children Dursun Alehan * Division of Pediatric Cardiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey Received 4 April 2003; received in revised form 27 August 2003; accepted 8 September 2003
Abstract Background: Ventricular noncompaction is a rare unclassified cardiomyopathy due to intrauterin arrest of compaction of the loose interwoven meshwork with limited data regarding diagnosis and outcome in children. Methods: In this study we describe clinical features of isolated left ventricular noncompaction (IVNC) in children and compare our findings with those previously reported. A diagnosis of ventricular noncompaction was made according to the characteristic echocardiographic appearance of two-layered myocardial wall consisting of a thin compacted epicardial and a thick noncompacted endocardial layer with numerous, prominent trabeculations and deep intertrabecular recesses communicating with left ventricular cavity. Results: Nine children, eight male and one female, with ages ranging from 10 days to 12 years and follow-up as long as 5 years were included into the study. The primary diagnosis of IVNC had been missed in four of the patients. Clinical manifestations were heart failure in five patients, cardiac murmur in two, dizziness in one, and palpitation in one patient. All patients, except two asymptomatic ones, had electrocardiographic abnormalities. Four patients required hospital admission for decompansated heart failure. Two patients died during follow-up while waiting for heart transplantation. Familial occurrence, ventricular tachycardia and thromboembolic events were not observed in any of the patients. Conclusions: Although IVNC is present at birth, it may become clinically overt at any time from infancy through adolescence. Physicians and echocardiographers should be familiar with the diagnostic pattern of ventricular noncompaction in order to prevent any delay in diagnosis. Since associated morbidity and mortality rates are high, these patients require regular follow-up. D 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Isolated ventricular noncompaction; Cardiomyopathy; Children; Echocardiography
1. Introduction Noncompaction of the ventricular myocardium is a rare congenital disorder categorized as unclassified cardiomyopathy by the World Health Organization [1]. It is believed to be due to an arrest in the normal endomyocardial embryogenesis, and may occur in isolation or may be associated with other congenital heart anomalies [2]. Characteristic echocardiographic findings consist of multiple, prominent myocardial trabeculations and deep intertrabecular recesses communicating with the ventricular cavity [3– 5]. Despite an increasing awareness and interest in this anomaly, knowledge regarding diagnosis and long-term prognosis in children is still limited. In this report, which represents the second largest pediatric population to date, we describe nine children with
* Sinan Caddesi, No. 115/4 Dikmen, 06450 Ankara, Turkey. Tel.: +90312-3104258; fax: +90-312-3090220. E-mail address: [email protected] (D. Alehan). 0167-5273/$ - see front matter D 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2003.09.004
isolated left ventricular noncompaction (IVNC) and compare our results with those of previous reports.
2. Methods The study group consisted of nine patients (eight males and one female) with ages ranging from 10 days to 12 years, seen in our department during a 4-year period ending in December 2002. The data included personal and family history, physical examination, 12-lead electrocardiogram (ECG), chest X-ray, two-dimensional echocardiogram with Doppler interrogation, and 24-h Holter recording. Additionally, patients 6 and 7 had intracardiac electrophysiological studies. Echocardiographic examination was performed in all patients according to the recommendations of the American Society of Echocardiography including two-dimensional guided M-mode measurements [6,7]. Distribution of prominent trabeculations in the ventricles was assessed using parasternal, apical, and subxiphoid imaging planes.
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D. Alehan / International Journal of Cardiology 97 (2004) 233–237
Echocardiopraphic data also included ventricular enddiastolic and end-systolic dimensions, fractional shortening, and ejection fraction. A diagnosis of isolated ventricular noncompaction was made according to the characteristic echocardiographic appearance of a twolayered structure of the myocardial wall consisting of a thin compacted epicardial layer and a thick noncompacted endocardial layer (ratio of noncompacted to compacted layers >2) with numerous, excessively prominent trabeculations and deep intertrabecular recesses communicating with the ventricular cavity [3– 5]. Echocardiograms were reviewed independetely by two pediatric cardiologists with expertise in echocardiography. Patients with coexisting cardiac abnormalities were excluded from the study.
3. Results 3.1. Clinical and electrocardiographic findings Clinical and electrocardiographic (ECG) characteristics of the patients are given in Table 1. Five patients presented with signs or symptoms of heart failure due to depressed left ventricular function. Two patients had no cardiac symptoms but was referred for evaluation of cardiac murmur. One patient presented with palpitation and dyspnea and one with dizziness. Familial occurrence or dysmorphic facial appearance were not observed in any of the patients. Patient 5 was the only patient with associated noncardiac malformations, and had esophageal atresia and tracheoesophageal fistula. Seven patients showed abnormalities on baseline ECG including left ventricular hypertrophy (based on voltage and repolarization criteria) and ST depression with flat or negative T waves in leads II, III, aVF and V4 – V6, prema-
Table 2 Echocardiographic findings of the patients at presentationa Case LVEDD (mm)
LFESD (mm)
EF SF Localization of (n: >55%) (n: 29 – 48%) noncompacted segments
1 2
35 (n: < 24) 30 (n: < 18) 29% 56 (n: < 40) 43 (n: < 27) 46%
13% 23%
3
55 (n: < 42) 40 (n: < 28) 46%
23%
4
47 (n: < 36) 41 (n: < 24) 26%
12%
5
20 (n: < 24) 12 (n: < 18) 68%
35%
6
62 (n: < 42) 55 (n: < 22) 24%
11%
7
43 (n: < 43) 27 (n: < 28) 68%
37%
8
54 (n: < 47) 41 (n: < 32) 48%
24%
9
18 (n: < 24) 12 (n: < 18) 69%
35%
LV apex LV apex, LW LV apex, LW LV apex, LW LV apex, LW LV apex, LW LV apex, LW LV apex, LW LV apex,
PW, PW, PW, PW, PW, PW, PW, PW
EF = ejection fraction; LV = left ventricle; LVEDD = left ventricle enddiastolic diameter; lVESD = left ventricle end-systolic diameter; LW = lateral wall; mm = millimeter; n = normal; PW = posterior wall; SF = shortening fraction. a Normal LV dimensions for children were obtained from Ref. [8].
ture ventricular contractions, and sinus bradycardia. Patients 5 and 9 were the only ones with a normal ECG. 3.2. Echocardiographic examinations Echocardiographic findings are summarized in Table 2. Two-dimensional echocardiograms showed numerous prominent trabeculations and deep intertrabecular recesses communicating with the ventricle in all nine patients (Figs. 1 and 2). Noncompacted myocardial segments were predominantly localized to the ventricular apex and posterior wall. Left ventricle was markedly dilated and left ventricular systolic function was severely depressed in six patients,
Table 1 Patient characteristics Case
Age at presentation
Weight (kg)
Gender
Clinical presentation
ECG
Associated findings
Follow-up (years)
Outcome
1 2
1,5 months 9 years
4.5 22
M M
Heart failure Heart failure
0 0
2 5
3 4 5
11 years 5 years 10 days
28 15.5 3
M M M
Heart failure Heart failure Murmur
LVH, ST-T wave changes LVH, ST-T wave changes Mobitz type II A-V block LVH, ST-T wave changes LVH, ST-T wave changes Normal
0 0 EA, TEF
3 3 1
6
7 years
24
M
LVH, ST-T wave changes PVC
0
5
7 8 9
12 years 12 years 1 month
30 45 4
M M F
Dispnea, palpitation Dizziness Heart failure Murmur
Died Pacemaker implantation, Died DSF DSF Surgery for EA and TEF, NSF DSF
Sinus bradycardia LVH, ST-T wave changes Normal
0 0 0
1 2.5 0.6
NSF DSF NSF
A-V = atrioventricular; CHD = congenital heart disease; DSF = decreased systolic function; EA = esophageal atresia; F = female; LVH = left vetricular hypertrophy; M = male; NSF = normal systolic function; PVC = premature ventricular contraction; TEF = tracheoesophageal fistula.
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whereas ventricle size and function were normal in three patients [8]. Intracardiac thrombus was not detected in any of the patients by echocardiography. The initial diagnosis of IVNC had been missed in four of our cases (patients 1, 2, 3 and 6). Delay in the diagnosis of IVNC was due to similarities between IVNC and other cardiomyopathies and to the examiner’s unfamilarity with its specific diagnostic pattern. Incorrect diagnosis was dilated cardiomyopathy in all of the patients. 3.3. Follow-up Mean duration of follow-up was 30.3 months (range: 6 –60 months). Hospital admission for severe heart failure was required in four patients. During follow-up, patient 2 developed Mobitz type II second-degree atrioventricular block with severe bradycardia and required permanent pacemaker implantation. He was hospitalized twice and died due to progressive ventricular dysfunction, 5 years after the initial diagnosis while waiting for heart transplantation. Patient 1 also died 2 years after the diagnosis because of severe heart failure. Patients 3, 4, 6 and 8 continued to have decreased systolic function and have been treated with digoxin, diuretics, and angiotensin-converting enzyme inhibitors. Additionally, they were given aspirin in an attempt to prevent thromboembolic events. Patient 5 underwent surgery for esophageal atresia and tracheoesophageal fistula. He and patient 9 had shown no symptoms related to cardiovascular system and had required no medication during the short follow-up period. Patient 7 had resting heart rates of < 50 beats/min and premature ventricular contractions (PVC) occurred during exercise testing in this patient. However, ventricular tachycardia was inducible neither in this patient nor in patient 5
Fig. 1. A representative two-dimensional echocardiogram in a patient with isolated ventricular noncompaction (patient 3). Parasternal long-axis view demonstrates a thin epicardial layer and an extremely thickened endocardial layer with prominent trabeculations and deep recesses in the apex and posterior wall of the left ventricle. LA: left atrium; LV: left ventricle.
Fig. 2. Modified parasternal long-axis view of patient 1. Two dimensional echocardiogram shows prominent trabeculations and deep recesses (arrows) in the apex of the left ventricle. LV: left ventricle.
(with PVC’s on surface ECG) during intracardiac electrophysiological study. Clinically overt thromboembolic events or ventricular tachycardia were not observed in any of the patients.
4. Discussion Isolated ventricular noncompaction is a rare cardiomyopathy with limited data regarding diagnosis and outcome in children. While echocardiography, magnetic resonance imaging, computed tomography, and angiography are all reliable imaging modalities to diagnose ventricular noncompaction, two-dimensional echocardiography with color and Doppler studies is the standard and first-line diagnostic tool [2,4,9 – 11]. However, for the correct diagnosis, the echocardiographer should be familiar with this congenital disorder and clear cut diagnostic criteria should be used. Despite an increasing awareness in this anomaly, there is still little knowledge regarding diagnosis of this rare cardiomyopathy. Indeed, the primary diagnosis of IVNC had been missed in four of our patients. The delay in diagnosis was due to the similarities between IVNC and other cardiomyopathies, and to the unfamilarity of the referring physicians with its specific diagnostic pattern. The incorrect diagnoses had been dilated cardiomyopathy in all of the patients. Other misdiagnoses reported in the literature include hypertrophic cardiomyopathy, restrictive cardiomyopthy, endocardial fibroelastosis and myocarditis [12,13]. Similar to our findings, Ichida et al. [13] also pointed out that the diagnosis of IVNC had been missed and several echocardiographic examinations had been required to diagnose IVNC in the majority of their cases. Left ventricular trabeculations have also been reported in 68% of normal hearts [14]. Thus the differentiation between variants and IVNC may be challenging in some
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cases. The characteristic discriminating feature to diagnose IVNC is the two-layered myocardial wall structure with both a thin epicardial compacted zone and an extremely thickened endocardial noncompacted zone with numerous and prominent trabeculations and deep recesses filled with blood from the ventricular cavity [3,5]. In the presence of these findings, a maximal end systolic ratio of noncompacted to compacted layers of >2 is diagnostic [3,5]. This rare abnormality is reported to be accompanied by three major risks, namely depressed ventricular function, endocardial clot with systemic embolization and ventricular arrhythmias that may be sometimes fatal [2]. The cause of depressed ventricular function is not clear. The coronary arteries are normal in these patients. However, recently restricted myocardial perfusion and decreased coronary flow reserve, suggestive of coronary microcirculatory dysfunction, were demonstrated by positron emission tomography in patients with IVNC [9,16]. Decreased coronary flow reserve was not only confined to noncompacted segments, but extended to most segments with wall motion abnormalities [16]. This finding suggests that coronary microcirculatory dysfunction may play a role in the development of impaired ventricular function [9,16]. Due to depressed ventricular function these patients usually present with heart failure similar to that of dilated cardiomyopathy. This was seen in six of our patients, in whom systolic function of the noncompacted myocardium was severely depressed. The patients described by Chin et al. [2] also manifested severe heart failure, ventricular tachycardia or embolic events at initial presentation and experienced a rapidly progressive clinical course. However, the current study differs from Chin’s study by absence of embolic events and ventricular tachycardia in Turkish children despite severely depressed ventricular functions. Our finding of no thromboembolic events may be due to small number of patient group or short follow-up period. Also the thromboembolic risk per se may be different in children from that in adults. Long-term studies with larger patient group may probably clarify the true thromboembolic risk in children. Ichida et al. [13] also reported many asymptomatic patients identified through mass screening who have longer clinical course with gradually depressed left ventricular function and restrictive hemodynamics. Their study is also characterized by absent systemic embolic events and very rare ventricular tachycardia in Japanese children. Our data and those of largest pediatric and adult series published so far are summarized in Table 3. Besides clinical features, the age range at diagnosis or onset of heart failure also varied widely in our study population as in previous studies [15]. Three of our patients, including one with heart failure, were diagnosed during neonatal period or early infancy whereas the others were asymptomatic until childhood. Thus, although IVNC is a congenital disorder and present at birth, its presentation may become clinically overt at any time from early infancy through adolescence.
Table 3 Characteristics of IVNC in the pediatric and adult population
Number of patients Age at diagnosis (median) Men Follow-up Facial dysmorphism Wolf – Parkinson – White syndrome Familial occurrence Heart failure symptom Systemic embolic events Deaths
Chin et al. [2]
Ichida et al. [13]
Present study
Oechslin et al. [3]
8 7 years
27 5 years
9 7 years
34 40 years
63% Up to 5 years 38% 13%
56% Up to 17 years 33% 15%
88% Up to 5 years 0% 0%
74% Up to 11 years 0% 0%
50% 63% 38% 38%
44% 30% 0% 7%
0% 56% 0% 22%
18% 68% 21% 35%
It is worth emphasizing that except two asymptomatic patients, all of our patients had an abnormal ECG at the time of presentation. In addition to baseline ECG abnormalities, patient 2 developed second-degree atrioventricular block requiring pacemaker implantation during follow-up. This suggests that ventricular conduction abnormalities may develop later in life and could be due to progressive endocardial fibrosis in association with IVNC [12,17]. Therefore regular follow-up is required for these patients. Our study revealed some features dissimilar to those previously reported in children. Although familial recurrences, facial dysmorphism and Wolff – Parkinson – White (WPW) syndrome were reported respectively in up to 50%, 38% and 15% of pediatric patients, they were absent in our patients [2,13,18,19]. Facial dysmorphism and WPW sydrome were also absent in a large adult population [3]. This clinical heterogeneity may be the result of different genetic background or genetic heterogeneity of this disorder, despite the same morphologic appearance of the cardiac anomaly [20,21]. Another interesting finding of the present study is the presence of esophageal atresia and tracheoesophageal fistula in one of our patients. Although IVNC may be associated with other noncardiac congenital malformations or syndromes, to our knowledge, this is the first association of this entity with esophageal atresia and tracheoesophageal fistula [22,23]. 4.1. Study limitations Our study population mostly consisted of patients referred to a tertiary care center because of heart failure. Therefore, there may be selection bias in this population representing mainly symptomatic patients. Also our study group is relatively small due to rare occurrence of IVNC. In conclusion, noncompaction of the ventricular myocardium is a rare congenital cardiomyopathy that may manifest itself from early infancy through adulthood with a wide clinical spectrum. Echocardiographers should be familiar
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with the diagnostic pattern of noncompaction in order to prevent any delay in diagnosis. Since associated morbidity and mortality rates are high, these patients require regular follow-up. As physicians become more aware of this rare disorder, the true prevalence and long-term prognosis of IVNC in an unselected group consisting of both asymptomatic and symptomatic patients will be better elucidated.
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