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Paradoxical Contributions of Non-Compacted and Compacted Segments to Global Left Ventricular Dysfunction in Isolated Left Ventricular Noncompaction
Paradoxical Contributions of Non-Compacted and Compacted Segments to Global Left Ventricular Dysfunction in Isolated Left Ventricular Noncompaction Carla Lofiego, MDa, Elena Biagini, MDa,b, Marinella Ferlito, MDa, Ferdinando Pasquale, MDa, Guido Rocchi, MDa, Enrica Perugini, MDa, Ornella Leone, MDc, Giovanni Bracchetti, MDa, Kadir Caliskan, MDb, Angelo Branzi, MDa, Folkert J. ten Cate, MDb, and Claudio Rapezzi, MDa,* The pathophysiologic mechanisms of left ventricular (LV) dysfunction in isolated ventricular noncompaction (IVNC) remain unclear. Evaluating global and segmental systolic LV function in 65 patients with IVNC, this study found that normal wall motion was more common in noncompacted than in compacted segments. The number of noncompacted segments per patient correlated positively with the LV ejection fraction and negatively with LV end-diastolic volume index. These paradoxical findings support the concept that noncompaction represents a marker of a more generalized (cardio)myopathy rather than the direct pathophysiologic substrate of this still little-understood disease. © 2006 Elsevier Inc. All rights reserved. (Am J Cardiol 2006;97:738 –741) Isolated ventricular noncompaction (IVNC) is a relatively new clinicopathologic entity (first described in 19901) characterized by a pattern of prominent trabecular meshwork and deep intertrabecular recesses communicating with the left ventricular (LV) cavity (see Figure 1). It has been hypothesized that IVNC results from the intrauterine arrest of the normal process of myocardial compaction, occurring independently of any ventricular pressure overload. Although a noncompacted myocardium is generally associated with the dilatation and hypokinesia of the left ventricle,1– 4 it has also been described in normally sized ventricles.2,5 IVNC still awaits nosographic definition.6 It is variously considered as a distinct (albeit currently unclassified) cardiomyopathy,6,7 as a subtype of dilated cardiomyopathy,8 or as a morphogenetic cardiac abnormality acting as a marker of coexisting neuromuscular disorders.7,9 The pathophysiologic mechanisms of the commonly associated LV dysfunction also remain unclear. In particular, it is not known whether myocardial dysfunction depends on the extension of the noncompacted segments. Hypokinesia seems not to be confined to the noncompacted zones, extending also to morphologically normal myocardium.3,10,11 To investigate whether myocardial noncompaction plays a direct pathophysiologic role in the LV dysfunction typically associated with IVNC, we evaluated the segmental systolic function of noncompacted and compacted segments and their rela-
a
Institute of Cardiology, University of Bologna, S. Orsola-Malpighi, Bologna, Italy; bThoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands; and cDepartment of Pathology, University of Bologna, Bologna, Italy. Manuscript received July 29, 2005; revised manuscript received and accepted September 13, 2005. * Corresponding author: Tel: 39-051349858; fax: 39-051344859. E-mail address: [email protected] (C. Rapezzi). 0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2005.09.109
tion with the LV ejection fraction in a series of patients with IVNC. •••
From January 1988 to September 2004, 65 patients (49 from Bologna, Italy, and 16 Rotterdam, The Netherlands) whose records were systematically recorded in our dedicated institutional databases satisfied stringent diagnostic criteria for IVNC. Briefly, specific echocardiographic diagnostic criteria were (in the absence of coexisting cardiac anomalies) (1) an excessively thickened myocardial wall with a 2-layered structure comprising a thin compacted layer on the epicardial side and a much thicker noncompacted layer of prominent trabeculations and deep intertrabecular recesses on the endocardial side; (2) a noncompacted/compacted myocardium thickness ratio ⬎2, as measured at the site of maximal thickness at the end-systolic phase of cardiac cycle3; and (3) color-Doppler evidence that the deep intertrabecular recesses were in communication with the ventricular cavity. For the purposes of the present study, we analyzed the most recent echocardiographic recordings (acquired from 1996 to 2004) of each of the 65 patients. Contrast echocardiography was used in 12 patients to clarify diagnostic ambiguities and optimize visualization of the endocardial border. LV volumes and ejection fractions were calculated in the apical 4-chamber view according to Simpson’s monoplane method, and a 16-segment model of the left ventricle was used to describe the localization of areas of noncompaction and regional contractility.12 The systolic performance of compacted and noncompacted segments was assessed using the wall motion score (WMS; 1 ⫽ normal motion, 2 ⫽ hypokinetic, 3 ⫽ akinetic, 4 ⫽ dyskinetic) and was expressed in terms of the WMS index (the WMS divided by the number of segments). In each center, measurements were performed by 2 experienced echocardiographers. The assessment of the interwww.AJConline.org
Miscellaneous/Segmental Function in Ventricular Compaction
739
Figure 1. Representative example of IVNC in an adult patient with dilated cardiomyopathy and congestive heart failure who underwent heart transplantation. The typical pattern of prominent trabecular meshwork and deep intertrabecular recesses communicating with the LV cavity is evident at echocardiography (upper portion; 4-chamber view), cross-sectional macroscopic examination (bottom left) and histology (bottom right, corresponding to the inset). Table 1 Clinical and echocardiographic characteristics (at the time of analysis) of 65 patients with isolated ventricular noncompaction Characteristic
Value
Age (yrs) 47 ⫾ 15 Women 41 (63%) NYHA class III/IV 18 (27%) Associated neuromuscular disease 6 (9%) LV end-diastolic diameter (mm) 67 ⫾ 12 124 ⫾ 52 LV end-diastolic volume (Simpson’s method) (ml/m2) LV ejection fraction (%) 32 ⫾ 10 Left atrial diameter (M-mode) (mm) 48 ⫾ 11 Moderate/severe mitral regurgitation 31 (47%) Noncompacted segments per patient 6 ⫾ 3 (median 5) Noncompacted/compacted ratio 2.7 ⫾ 0.7 Restrictive LV filling pattern 19 (29%) Data are expressed as mean ⫾ SD or as number of patients (percentage). NYHA ⫽ New York Heart Association.
and intraobserver variability of the WMS was determined by 2 independent observers at 2 different readings 20 days apart (analyzed according to statistics).
The patients’ main clinical and echocardiographic characteristics at the time of analysis are listed in Table 1. Of note, the diagnostic route was symptom based in 48 patients (74%; including 40 with heart failure symptoms), whereas in the remaining patients, diagnosis was either incidental (n ⫽ 7) or through family referral (n ⫽ 10). At the time of the echocardiographic examinations considered in this analysis, all the patients were in sinus rhythm, 21 had left bundle branch blocks, and 55 were receiving medical therapy (warfarin, n ⫽ 29;  blockers, n ⫽ 38; angiotensin-converting enzyme inhibitors, n ⫽ 48; and diuretics, n ⫽ 27). In 53 patients (82%), IVNC was associated with variable degrees of LV dilatation and hypokinesia, whereas in the remaining 12 patients (18%), LV volumes were normal. Of the 1,040 segments assessed, 364 (35%) were noncompacted; Figure 2 shows their distribution according to the 16-segment model. The WMS could be evaluated in 995 segments (96%); intra- and interobserver agreements were 95% ( ⫽ 0.90). The WMS index was significantly less in noncompacted than in compacted segments (1.91 ⫾ 0.45 vs 2.10 ⫾
740
The American Journal of Cardiology (www.AJConline.org)
Figure 2. Distribution of IVNC according to the 16-segment model. Table 2 Comparison of wall motion characteristics in noncompacted and compacted segments Wall Motion
Noncompacted Segments (n ⫽ 346)
Compacted Segments (n ⫽ 649)
p Value (Chi-square Test)
Normal Hypokinetic Akinetic Dyskinetic
86 (25%) 218 (63%) 38 (11%) 4 (1%)
78 (12%) 429 (66%) 123 (19%) 19 (3%)
⬍0.0001 0.31 0.001 0.168
0.44, p ⫽ 0.01). Table 2 reports the characteristics of wall motion contractility in these 2 subgroups. Relations between segmental and global systolic function were analyzed (Figure 3): the number of noncompacted segments per patient correlated positively with the LV ejection fraction (R ⫽ 0.38, p ⫽ 0.002) and negatively with LV end-diastolic volume index (R ⫽ ⫺0.34, p ⬍0.005). Furthermore, the mean LV ejection fraction was greater in the subgroup of patients (n ⫽ 28) with more than the median number (i.e., ⬎5) of noncompacted segments (36 ⫾ 13% vs 27 ⫾ 8%, p ⫽ 0.002). Of note, these relations were not statistically apparent when the patients with (n ⫽ 53) and without (n ⫽ 12) depressed LV function (ejection fraction ⬍40%) were considered separately. •••
This systematic analysis of the relative contributions of noncompacted and compacted segments to global LV function in IVNC was performed in a series of patients with wide-ranging clinical pictures and LV function profiles. The results indicate that the noncompacted and compacted segments provide different contributions to the overall LV dysfunction that pathophysiologically characterizes most (although not all) patients with IVNC. In a disease characterized by a specific morphologic feature (noncompaction), one might legitimately expect a positive correlation between the extent of this abnormality and the overall LV dysfunction. Paradoxically, however, in
Figure 3. Correlations between numbers of noncompacted segments per patient and (A) the LV ejection fraction and (B) LV end-diastolic volume.
our series of patients, the noncompacted segments showed better performance than the morphologically normal ones in terms of the WMS. When interpreting these findings, it must be remembered that the noncompacted segments are also more hypertrophic than their morphologically normal counterparts.1,5,7 So, the better WMS index recorded in the noncompacted segments could merely reflect their likely lower parietal stress (an unmeasured variable) rather than normal or slightly depressed contractility. Strain rate analysis could be included in future studies to clarify this point. More generally, our results seem to be in line with the hypothesis7–9 that IVNC is part of a more widespread cardiomyopathy, involving the morphologically normal and the dysmorphic segments. Interestingly, in a study focusing on coronary flow reserve (another determinant of myocardial function) Jenni et al10 found that abnormalities were not confined to noncompacted segments but extended to most morphologically normal segments. Some caution is required when interpreting the results of the present study, because the coexistence of overt dilated cardiomyopathy might have facilitated the recognition of noncompacted segments (which might be more difficult to spot in normal-sized ventricles),
Miscellaneous/Segmental Function in Ventricular Compaction
biasing recruitment toward patients with more severe systolic dysfunction. Our data are not readily comparable with those of previous reports. In our patients, abnormal regional wall motion was predominant but not universal (see Table 2). Other studies that generated descriptive data on segmental wall motion in IVNC3,10,11 had different main aims, and they were conducted in series of patients who were almost always symptomatic and had the pathophysiologic characteristics of dilated cardiomyopathy. This may help explain why Sengupta et al,11 Jenni et al,10 and Oechslin et al3 all found that the noncompacted segments under study were invariably hypokinetic, with the prevalence of hypokinesia in the compacted segments ranging from 58% to 66%. Other possible explanations for the discrepancies include the use of a 16-segment model and the use of contrast echocardiography. In fact, the difficulty of obtaining truly adequate visualization of the endocardial border and its motion remains the major technical limitation of any study dealing with segmental wall motion in IVNC. 1. Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R. Isolated noncompaction of left ventricular myocardium. A study of eight cases. Circulation 1990;82:507–513. 2. Ichida F, Hamamichi Y, Miyawaki T, Ono Y, Kamiya T, Akagi T, Hamada H, Hirose O, Isobe T, Yamada K, 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;34:233–240. 3. Oechslin EN, Attenhofer Jost CH, Rojas JR, Kaufmann PA, Jenni R. Long-term follow-up of 34 adults with isolated left ventricular non-
4.
5. 6.
7. 8.
9.
10.
11.
12.
741
compaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol 2000;36:493–500. Pignatelli RH, McMahon CJ, Dreyer WJ, Denfield SW, Price J, Belmont JW, Craigen WJ, Wu J, El Said H, Bezold LI, et al. Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy. Circulation 2003; 108:2672–2678. Burke A, Mont E, Kutys R, Virmani R. Left ventricular noncompaction: a pathological study of 14 cases. Hum Pathol 2005;36:403– 411. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies. Circulation 1996;93:841– 842. Weiford BC, Subbarao VD, Mulhern KM. Noncompaction of the ventricular myocardium. Circulation 2004;109:2965–2971. Murphy RT, Thaman R, Blanes JG, Ward D, Sevdalis E, Papra E, Kiotsekolglou A, Tome MT, Pellerin D, McKenna WJ, et al. Natural history and familial characteristics of isolated left ventricular noncompaction. Eur Heart J 2005;26:187–192. Stollberger C, Winkler-Dworak M, Blazek G, Finsterer J. Left ventricular hypertrabeculation/noncompaction with and without neuromuscular disorders. Int J Cardiol 2004;97:89 –92. Jenni R, Wyss CA, Oechslin EN, Kaufmann PA. Isolated ventricular noncompaction is associated with coronary microcirculatory dysfunction. J Am Coll Cardiol 2002;39:450 – 454. Sengupta PP, Mohan JC, Mehta V, Jain V, Arora R, Pandian NG, Khandheria BK. Comparison of echocardiographic features of noncompaction of the left ventricle in adults versus idiopathic dilated cardiomyopathy in adults. Am J Cardiol 2004;94:389 –391. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358 –367.
a
Institute of Cardiology, University of Bologna, S. Orsola-Malpighi, Bologna, Italy; bThoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands; and cDepartment of Pathology, University of Bologna, Bologna, Italy. Manuscript received July 29, 2005; revised manuscript received and accepted September 13, 2005. * Corresponding author: Tel: 39-051349858; fax: 39-051344859. E-mail address: [email protected] (C. Rapezzi). 0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2005.09.109
tion with the LV ejection fraction in a series of patients with IVNC. •••
From January 1988 to September 2004, 65 patients (49 from Bologna, Italy, and 16 Rotterdam, The Netherlands) whose records were systematically recorded in our dedicated institutional databases satisfied stringent diagnostic criteria for IVNC. Briefly, specific echocardiographic diagnostic criteria were (in the absence of coexisting cardiac anomalies) (1) an excessively thickened myocardial wall with a 2-layered structure comprising a thin compacted layer on the epicardial side and a much thicker noncompacted layer of prominent trabeculations and deep intertrabecular recesses on the endocardial side; (2) a noncompacted/compacted myocardium thickness ratio ⬎2, as measured at the site of maximal thickness at the end-systolic phase of cardiac cycle3; and (3) color-Doppler evidence that the deep intertrabecular recesses were in communication with the ventricular cavity. For the purposes of the present study, we analyzed the most recent echocardiographic recordings (acquired from 1996 to 2004) of each of the 65 patients. Contrast echocardiography was used in 12 patients to clarify diagnostic ambiguities and optimize visualization of the endocardial border. LV volumes and ejection fractions were calculated in the apical 4-chamber view according to Simpson’s monoplane method, and a 16-segment model of the left ventricle was used to describe the localization of areas of noncompaction and regional contractility.12 The systolic performance of compacted and noncompacted segments was assessed using the wall motion score (WMS; 1 ⫽ normal motion, 2 ⫽ hypokinetic, 3 ⫽ akinetic, 4 ⫽ dyskinetic) and was expressed in terms of the WMS index (the WMS divided by the number of segments). In each center, measurements were performed by 2 experienced echocardiographers. The assessment of the interwww.AJConline.org
Miscellaneous/Segmental Function in Ventricular Compaction
739
Figure 1. Representative example of IVNC in an adult patient with dilated cardiomyopathy and congestive heart failure who underwent heart transplantation. The typical pattern of prominent trabecular meshwork and deep intertrabecular recesses communicating with the LV cavity is evident at echocardiography (upper portion; 4-chamber view), cross-sectional macroscopic examination (bottom left) and histology (bottom right, corresponding to the inset). Table 1 Clinical and echocardiographic characteristics (at the time of analysis) of 65 patients with isolated ventricular noncompaction Characteristic
Value
Age (yrs) 47 ⫾ 15 Women 41 (63%) NYHA class III/IV 18 (27%) Associated neuromuscular disease 6 (9%) LV end-diastolic diameter (mm) 67 ⫾ 12 124 ⫾ 52 LV end-diastolic volume (Simpson’s method) (ml/m2) LV ejection fraction (%) 32 ⫾ 10 Left atrial diameter (M-mode) (mm) 48 ⫾ 11 Moderate/severe mitral regurgitation 31 (47%) Noncompacted segments per patient 6 ⫾ 3 (median 5) Noncompacted/compacted ratio 2.7 ⫾ 0.7 Restrictive LV filling pattern 19 (29%) Data are expressed as mean ⫾ SD or as number of patients (percentage). NYHA ⫽ New York Heart Association.
and intraobserver variability of the WMS was determined by 2 independent observers at 2 different readings 20 days apart (analyzed according to statistics).
The patients’ main clinical and echocardiographic characteristics at the time of analysis are listed in Table 1. Of note, the diagnostic route was symptom based in 48 patients (74%; including 40 with heart failure symptoms), whereas in the remaining patients, diagnosis was either incidental (n ⫽ 7) or through family referral (n ⫽ 10). At the time of the echocardiographic examinations considered in this analysis, all the patients were in sinus rhythm, 21 had left bundle branch blocks, and 55 were receiving medical therapy (warfarin, n ⫽ 29;  blockers, n ⫽ 38; angiotensin-converting enzyme inhibitors, n ⫽ 48; and diuretics, n ⫽ 27). In 53 patients (82%), IVNC was associated with variable degrees of LV dilatation and hypokinesia, whereas in the remaining 12 patients (18%), LV volumes were normal. Of the 1,040 segments assessed, 364 (35%) were noncompacted; Figure 2 shows their distribution according to the 16-segment model. The WMS could be evaluated in 995 segments (96%); intra- and interobserver agreements were 95% ( ⫽ 0.90). The WMS index was significantly less in noncompacted than in compacted segments (1.91 ⫾ 0.45 vs 2.10 ⫾
740
The American Journal of Cardiology (www.AJConline.org)
Figure 2. Distribution of IVNC according to the 16-segment model. Table 2 Comparison of wall motion characteristics in noncompacted and compacted segments Wall Motion
Noncompacted Segments (n ⫽ 346)
Compacted Segments (n ⫽ 649)
p Value (Chi-square Test)
Normal Hypokinetic Akinetic Dyskinetic
86 (25%) 218 (63%) 38 (11%) 4 (1%)
78 (12%) 429 (66%) 123 (19%) 19 (3%)
⬍0.0001 0.31 0.001 0.168
0.44, p ⫽ 0.01). Table 2 reports the characteristics of wall motion contractility in these 2 subgroups. Relations between segmental and global systolic function were analyzed (Figure 3): the number of noncompacted segments per patient correlated positively with the LV ejection fraction (R ⫽ 0.38, p ⫽ 0.002) and negatively with LV end-diastolic volume index (R ⫽ ⫺0.34, p ⬍0.005). Furthermore, the mean LV ejection fraction was greater in the subgroup of patients (n ⫽ 28) with more than the median number (i.e., ⬎5) of noncompacted segments (36 ⫾ 13% vs 27 ⫾ 8%, p ⫽ 0.002). Of note, these relations were not statistically apparent when the patients with (n ⫽ 53) and without (n ⫽ 12) depressed LV function (ejection fraction ⬍40%) were considered separately. •••
This systematic analysis of the relative contributions of noncompacted and compacted segments to global LV function in IVNC was performed in a series of patients with wide-ranging clinical pictures and LV function profiles. The results indicate that the noncompacted and compacted segments provide different contributions to the overall LV dysfunction that pathophysiologically characterizes most (although not all) patients with IVNC. In a disease characterized by a specific morphologic feature (noncompaction), one might legitimately expect a positive correlation between the extent of this abnormality and the overall LV dysfunction. Paradoxically, however, in
Figure 3. Correlations between numbers of noncompacted segments per patient and (A) the LV ejection fraction and (B) LV end-diastolic volume.
our series of patients, the noncompacted segments showed better performance than the morphologically normal ones in terms of the WMS. When interpreting these findings, it must be remembered that the noncompacted segments are also more hypertrophic than their morphologically normal counterparts.1,5,7 So, the better WMS index recorded in the noncompacted segments could merely reflect their likely lower parietal stress (an unmeasured variable) rather than normal or slightly depressed contractility. Strain rate analysis could be included in future studies to clarify this point. More generally, our results seem to be in line with the hypothesis7–9 that IVNC is part of a more widespread cardiomyopathy, involving the morphologically normal and the dysmorphic segments. Interestingly, in a study focusing on coronary flow reserve (another determinant of myocardial function) Jenni et al10 found that abnormalities were not confined to noncompacted segments but extended to most morphologically normal segments. Some caution is required when interpreting the results of the present study, because the coexistence of overt dilated cardiomyopathy might have facilitated the recognition of noncompacted segments (which might be more difficult to spot in normal-sized ventricles),
Miscellaneous/Segmental Function in Ventricular Compaction
biasing recruitment toward patients with more severe systolic dysfunction. Our data are not readily comparable with those of previous reports. In our patients, abnormal regional wall motion was predominant but not universal (see Table 2). Other studies that generated descriptive data on segmental wall motion in IVNC3,10,11 had different main aims, and they were conducted in series of patients who were almost always symptomatic and had the pathophysiologic characteristics of dilated cardiomyopathy. This may help explain why Sengupta et al,11 Jenni et al,10 and Oechslin et al3 all found that the noncompacted segments under study were invariably hypokinetic, with the prevalence of hypokinesia in the compacted segments ranging from 58% to 66%. Other possible explanations for the discrepancies include the use of a 16-segment model and the use of contrast echocardiography. In fact, the difficulty of obtaining truly adequate visualization of the endocardial border and its motion remains the major technical limitation of any study dealing with segmental wall motion in IVNC. 1. Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R. Isolated noncompaction of left ventricular myocardium. A study of eight cases. Circulation 1990;82:507–513. 2. Ichida F, Hamamichi Y, Miyawaki T, Ono Y, Kamiya T, Akagi T, Hamada H, Hirose O, Isobe T, Yamada K, 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;34:233–240. 3. Oechslin EN, Attenhofer Jost CH, Rojas JR, Kaufmann PA, Jenni R. Long-term follow-up of 34 adults with isolated left ventricular non-
4.
5. 6.
7. 8.
9.
10.
11.
12.
741
compaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol 2000;36:493–500. Pignatelli RH, McMahon CJ, Dreyer WJ, Denfield SW, Price J, Belmont JW, Craigen WJ, Wu J, El Said H, Bezold LI, et al. Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy. Circulation 2003; 108:2672–2678. Burke A, Mont E, Kutys R, Virmani R. Left ventricular noncompaction: a pathological study of 14 cases. Hum Pathol 2005;36:403– 411. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies. Circulation 1996;93:841– 842. Weiford BC, Subbarao VD, Mulhern KM. Noncompaction of the ventricular myocardium. Circulation 2004;109:2965–2971. Murphy RT, Thaman R, Blanes JG, Ward D, Sevdalis E, Papra E, Kiotsekolglou A, Tome MT, Pellerin D, McKenna WJ, et al. Natural history and familial characteristics of isolated left ventricular noncompaction. Eur Heart J 2005;26:187–192. Stollberger C, Winkler-Dworak M, Blazek G, Finsterer J. Left ventricular hypertrabeculation/noncompaction with and without neuromuscular disorders. Int J Cardiol 2004;97:89 –92. Jenni R, Wyss CA, Oechslin EN, Kaufmann PA. Isolated ventricular noncompaction is associated with coronary microcirculatory dysfunction. J Am Coll Cardiol 2002;39:450 – 454. Sengupta PP, Mohan JC, Mehta V, Jain V, Arora R, Pandian NG, Khandheria BK. Comparison of echocardiographic features of noncompaction of the left ventricle in adults versus idiopathic dilated cardiomyopathy in adults. Am J Cardiol 2004;94:389 –391. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358 –367.