CORRESPONDENCE Left Ventricular Noncompaction Cardiomyopathy: Lessons from the Past to Explain a Diagnostic Conundrum To the Editor: Those who fail to learn from history are doomed to repeat it. —Sir Winston Churchill Left ventricular (LV) noncompaction (LVNC) is a myocardial disorder characterized by pathognomonic morphologic anatomic features, including a thick, bilayered (compacted and noncompacted) myocardium; prominent ventricular trabeculations (spongy appearance); and deep intertrabecular recesses extending from the LV cavity to the subendocardial surface of the LV wall.1 These distinct morphologic features result from an arrest of myocardial maturation during embryogenesis.2 LVNC is accompanied by LV dysfunction, leading to heart failure, arrhythmias, thromboembolic events, and sudden cardiac death.3 Determining which patients are at risk for these complications has remained an enigma because of the heterogeneous expression of this entity. With the widespread use of echocardiography and increased awareness of LVNC, more patients are meeting the diagnostic criteria of LVNC (i.e., bilayered ‘‘spongy-looking’’ myocardium with a ratio of noncompacted to compacted myocardium > 2.0). However, in some of these individuals, LV function and myocardial mechanics are normal (i.e., not only a normal LV ejection fraction but also normal diastolic functional parameters, tissue Doppler and speckle-tracking parameters, strain, strain rate, and LV twist and rotation). So what do these individuals have? The query is whether this represents the early stages of LVNC cardiomyopathy, simply a ‘‘benign’’ phenotype of LVNC, or is perhaps best referred to as LV hypertrabeculation (LVHT). Recently, Arbustini et al.4 proposed a nosology, MOGE(S), that may improve our recognition and clinical acumen and enrich our understanding of cardiomyopathies. The proposed nosology is comprehensive, classifying five features of each cardiomyopathy: morphofunction phenotype (M), organ involvement (O), genetic or familial inheritance pattern (G), etiologic annotation (E), and function classification (S). This system may make it possible to distinguish LVNC with LV dilation and LV dysfunction (MLVNC+D) or hypertrophy (MLVNC+ H) from pure LVNC (MLVNC/LVHT).4 These distinctions are not made or emphasized in any of the diagnostic criteria defining LVNC. There are four different diagnostic criteria for LVNC published in the literature, the earliest dating back more than 20 years,5 but no universally accepted sensitive and specific definition of how to diagnose LVNC. All the available diagnostic criteria are based on a bilayered myocardial morphology, and three of the four criteria focus on ratios of noncompacted and compacted myocardium.1,5-7 The current diagnostic criteria have limitations, as they do not distinguish MLVNC from LVNC cardiomyopathy and were not generated prospectively, and validation techniques were not rigorous. This introduces a clinical dilemma. Is MLVNC/LVHT a disease or simply an anatomic remnant? Currently, there is no marker to identify if or when MLVNC will transition to a disease state (MLVNC+D). The pendulum has swung away from LVNC’s being a rare disease. Since 2000, LVNC has become an increasingly recognized diagnosis, with 862 publications on the topic, according to the US National Library of Medicine and National Institutes of Health. The number of publications in 2000 was four, compared with 134 in 2013. In the past 4 years at our institution, LVNC has been increasingly diagnosed. Our institution identified 65 cases of LVNC (0.4% of total 1128
echocardiographic examinations) in 2010 and 181 cases (1.0% of total echocardiographic examinations) in 2013. The pendulum swing raises a concern that we may have transitioned from under- to overdiagnosis as the result perhaps of arbitrary diagnostic criteria. DIAGNOSTIC CONUNDRUM Kohli et al.8 tested the echocardiographic criteria of Chin et al.,5 Jenni et al.,1 and St€ ollberger and Finsterer9 in patients with definitive LVNC. There was poor correlation among the three echocardiographic definitions, with only 30% of patients fulfilling all three criteria.8 Furthermore, Kohli et al. found that 8% of controls (four black subjects and one white subject) met at least one of the three criteria to diagnose LVNC. The review highlights the concern that the current echocardiographic criteria may be overly sensitive, particularly in black individuals, resulting in overdiagnosis of LVNC. This concern is further reified by a Mayo Clinic series in which 25% of patients with echocardiographic diagnoses of LVNC did not meet diagnostic criteria after careful retrospective review by two experts from the same echocardiography laboratory.10 This raises a serious concern of overdiagnosis (false positives) of LVNC in the practices of echocardiographic laboratories, with a negative impact of diagnosis on patients’ lives. Additional support for the diagnostic conundrum is the pathologic definition of LVNC as described by Burke et al.11 and Freedom et al.12 Freedom et al. described the unique anatomic features of hearts explanted from patients with LVNC. The hearts revealed a luminal meshwork of thin and thick endocardial bands, tendons, filaments, and trabeculations that intermixed to form a discrete trabecular layer of the LV wall to its apex. The thick and coarse trabeculations of the trabecular layer were separated by deep recesses. They did not use ratios to identify LVNC. Burke et al. described 14 explanted hearts with LVNC (nine of 14 sudden cardiac deaths). The pathologic definition included poorly developed papillary muscles and a noncompacted inner LV myocardial layer that comprised > 50% of the LV thickness. An important finding to note is that in four of 14 cases (27%), the noncompacted/compacted myocardial ratio was < 2. The statistic that 27% of patients with pathoanatomic diagnoses of LVNC did not meet an arbitrary cutoff ratio of noncompacted to compacted myocardium > 2 reinforces the limitation of diagnosing LVNC solely on the basis of measurements of ratios. We are at the precipice of a slippery slope of labeling people without a disease as having a serious disease entity. This is deja vu, because a similar chasm was scaled with asymmetric septal hypertrophy (ASH) and hypertrophic cardiomyopathy (HCM). The recognition that HCM could not be defined by diagnostic criteria using only measurements and an arbitrary ratio resulted in the withering of ASH as pathognomonic of HCM. Churchill’s quotation should resonate in our approach to obtain a deeper understanding of the LVNC spectrum. Lessons learned from a historical review of the measurements and ratios used to validate a diagnosis of HCM may prevent us from repeating the same errors. We present how the lesson of the experience with ASH and HCM could apply to LVNC.
HISTORICAL LESSONS: ASYMMETRIC SEPTAL HYPERTROPHY Four decades ago, in 1974, Henry and colleagues published their finding that ASH was a sensitive and specific disease marker of
Correspondence 1129
Journal of the American Society of Echocardiography Volume 27 Number 10
idiopathic hypertrophic subaortic stenosis. ASH was characterized by a ventricular septum that was $ 1.3 times as thick as the posterior LV free wall.13-15 They concluded that ASH was a pathognomonic anatomic abnormality of idiopathic hypertrophic subaortic stenosis.16 The observation that ASH was possible even with a normal thickness of the septum resulted in many normal individuals’ being incorrectly diagnosed with idiopathic hypertrophic subaortic stenosis (e.g., ventricular septum 12 mm, posterior wall 9 mm). With the introduction of two-dimensional echocardiography, the diseaseidentifying ratio went from ASH to disproportionate upper septal thickness. However, soon disproportionate upper septal thickness also was noted in systemic hypertension, pulmonary hypertension, valvular heart disease, and coarctation of the aorta.13 The lack of a true criterion standard, such as a genetic marker, to identify LVNC and its heterogeneous phenotypic expressions has inhibited our ability to determine a valid, reproducible definition. Furthermore, our inability to define whether a hypertrabeculated phenotype MLVNC/LVHT will transition to a cardiomyopathy complicates the issue. Thus, diagnosing the difference between the variant characterized by prominent apical trabeculations, MLVNC/LVHT, and MLVNC+D or MLVNC+H poses a new challenge to the medical community. A diagnostic modality ensuring a valid diagnosis of LVNC as reliably as a genetic marker has remained elusive. Measurement of not only morphologic features but also of advanced echocardiographic parameters, such as strain, strain rate, displacement, rotation, torsion, and deformation, currently has not achieved this dream.17-21 The main lesson learned from a temporal review of HCM that lends insight to the spectrum of LVNC is that disease should not be defined by measurements and ratios in isolation. Historically, the entity LVNC was described and studied in patients with abnormal systolic function. In 1990, Chin et al.5 described their echocardiographic findings in eight patients with isolated LVNC. Five of the eight patients had depressed LV systolic function. Jenni et al.1 in 2001 reviewed 34 adult patients with LVNC. Seven hearts were available for anatomic review through heart transplantation (three patients) or autopsy (four patients). LV ejection fractions ranged from 29% to 38% in these seven patients. A recent study in France reviewed the clinical and echocardiographic features of 105 patients with LVNC.22 Of these patients, 84% had reduced LV ejection fractions. These three studies reveal that the ratio-based criteria to diagnose LVNC were derived from diseased myopathic ventricles. We must not repeat the historical mistakes made with ASH and rely on an arbitrary ratio to diagnose HCM. Analysis must be multivariate to prevent under- and overdiagnosis. The diagnostic tools must have clinical application that is sensitive and specific to allow a distinction between normal anatomic variants, MLVNC/LVHT, and diseasestate MLVNC+D or MLVNC+H. BEYOND MEASUREMENTS AND RATIOS The present diagnostic tools result in uncertainty, as the noncompacted/compacted myocardial ratio has limitations, and the extent of noncompacted LV areas cannot distinguish with certainty disease from a variation of normal anatomy. Available studies have identified conflicting results: that the degree of LVNC is not related to the severity of LV systolic dysfunction23,24 and that the degree of LVNC is related to the degree of LV dysfunction.22,25 One study observed myocardial fibrosis in noncompacted and compacted myocardial segments with similar prevalence, supporting the theory that noncompacted myocardium is a phenotypic marker of an
underlying diffuse cardiomyopathy involving both noncompacted and compacted myocardium.26 These findings need further investigation and validation. Where do we go from here? Recent research suggests that maximal systolic compacta thickness < 8 mm is specific for LVNC, allowing differentiation from normal hearts and myocardial thickening due to pressure overload, and may be used as an additional diagnostic criteria.27 Peters et al.28 found that LV twist is diminished in subjects with LVNC and normal rotation. Rigid body rotation occurred in 53% of patients (32 of 60) with LVNC. Captur et al.29 identified that fractal analysis of trabeculations may aid in distinguishing healthy volunteers from patients with LVNC and that fractal dimension of trabeculations is greater in healthy blacks than whites. Despite these incremental advances, we are still left without a definitive way to diagnose LVNC. Current diagnostic criteria alone appear inadequate to make or refute the diagnosis of LVNC definitively.30 NEXT STEPS The search for more definitive diagnostic tools must continue with collaboration among large medical centers. There is a need for an LVNC consensus group to forge the path to a deeper understanding of this complex cardiomyopathy through international registries and multicenter collaboration. The collaboration must include the cross-pollination of ideas from the fields of embryology, genetics, and imaging. The use of a common nomenclature such as MOGE(S) will be advantageous. CONCLUSIONS Clearly, all present-day advances leave us wanting for a more sensitive and specific way of distinguishing MLVNC/LVHT from the disease state of LVNC cardiomyopathy. The interpretation and diagnosis must extend beyond measurements and ratios, as identified when we went from ASH to HCM. We must distinguish MLVNC/LVHT from MLVNC+D or MLVNC+H to prevent overdiagnosis. Ultimately, the genetic diagnosis of different types of HCM became a reality. Hopefully, the genetics of LVNC also will become a reality. The criteria finally chosen and accepted to diagnose LVNC must incorporate all aspects of MOGE(S). In daily practice, we must approach the diagnosis with broad clinical perspective. The judicious use of echocardiography and magnetic resonance imaging by thoughtful clinicians should allow accurate diagnosis, appropriate follow-up, and prognostication. When the cardiomyopathy is identified, we must follow patients carefully for heart failure, rhythm disturbances, and neurologic symptoms. When M LVNC/LVHT is identified, we need surveillance with echocardiography to determine if there is transition to the cardiomyopathy. As Churchill so eloquently advised, we must learn from history to avoid repeating the same error in the diagnosis of LVNC using a ratio (noncompacted/compacted myocardium > 2.0) that was made with HCM using ASH (ventricular septum/ posterior wall > 1.3) as a ratio.
Timothy E. Paterick, MD, JD A. Jamil Tajik, MD Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke’s Medical Centers, University of Wisconsin School of Medicine and Public Health, Milwaukee, Wisconsin
1130 Correspondence
REFERENCES 1. 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. 2. Wessels A, Sedmera D. Developmental anatomy of the heart: a tale of mice and man. Physiol Genomics 2003;15:165-76. 3. Paterick TE, Gerber TC, Pradhan SR, Lindor NM, Tajik AJ. Left ventricular noncompaction cardiomyopathy: what do we know? Rev Cardiovasc Med 2010;11:92-9. 4. Arbustini E, Narula N, Dec GW, Reddy KS, Greenberg B, Kushwaha S, et al. The MOGE(S) classification for a phenotype-genotype nomenclature of cardiomyopathy: endorsed by the World Heart Federation. J Am Coll Cardiol 2013;62:2046-72. 5. 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. 6. St€ ollberger C, Finsterer J, Blazek G. Left ventricular hypertrabeculation/noncompaction and association with additional cardiac abnormalities and neuromuscular disorders. Am J Cardiol 2002;90: 899-902. 7. Paterick TE, Umland MM, Jan MF, Ammar KA, Kramer C, Khandheria BK, et al. Left ventricular noncompaction: a 25-year odyssey. J Am Soc Echocardiogr 2012;25:363-75. 8. Kohli SK, Pantazis AA, Shah JS, Adeyemi B, Jackson G, McKenna WJ, et al. Diagnosis of left-ventricular non-compaction in patients with leftventricular systolic dysfunction: time for a reappraisal of diagnostic criteria? Eur Heart J 2008;29:89-95. 9. St€ ollberger C, Finsterer J. Left ventricular hypertrabeculation/noncompaction. J Am Soc Echocardiogr 2004;17:91-100. 10. Stanton C, Bruce C, Connolly H, Brady P, Syed I, Hodge D, et al. Isolated left ventricular noncompaction syndrome. Am J Cardiol 2009;104: 1135-8. 11. Burke A, Mont E, Kutys R, Virmani R. Left ventricular noncompaction: a pathological study of 14 cases. Hum Pathol 2005;36:403-11. 12. Freedom RM, Yoo SJ, Perrin D, Taylor G, Petersen S, Anderson RH. The morphological spectrum of ventricular noncompaction. Cardiol Young 2005;15:345-64. 13. Kansal S, Roitman D, Sheffield LT. Interventricular septal thickness and left ventricular hypertrophy. An echocardiographic study. Circulation 1979; 60:1058-65. 14. Epstein SE, Henry WL, Clark CE, Roberts WC, Maron BJ, Ferrans VJ, et al. Asymmetric septal hypertrophy. Ann Intern Med 1974;81:650-80. 15. Williams LK, Frenneaux MP, Steeds RP. Echocardiography in hypertrophic cardiomyopathy diagnosis, prognosis, and role in management. Eur J Echocardiogr 2009;10:iii9-14. 16. Henry WL, Clark CE, Epstein SE. Asymmetric septal hypertrophy. Echocardiographic identification of the pathognomonic anatomic abnormality of IHSS. Circulation 1973;47:225-33. 17. Paterick TE, Tajik AJ. Left ventricular noncompaction. Circ J 2012;76: 1556-62. 18. St€ ollberger C, Gerecke B, Finsterer J, Engberding R. Refinement of echocardiographic criteria for left ventricular noncompaction. Int J Cardiol 2013;165:463-7. 19. Willemsen HM, van den Berg MP. A few more pieces in the puzzle of noncompaction cardiomyopathy. Eur J Heart Fail 2011;13:127-9. 20. Attenhofer Jost CH, Connolly HM. Left ventricular non-compaction: dreaming of the perfect diagnostic tool. Eur J Heart Fail 2012;14:113-4. 21. Peters F, Khandheria BK. Isolated left ventricular noncompaction: what do we really know? Curr Cardiol Rep 2012;14:381-8. 22. Habib G, Charron P, Eicher JC, Giorgi R, Donal E, Laperche T, et al. Isolated left ventricular non-compaction in adults: clinical and echocardiographic features in 105 patients. Results from a French registry. Eur J Heart Fail 2011;13:177-85.
Journal of the American Society of Echocardiography October 2014
23. Aras D, Tufekcioglu O, Ergun K, Ozeke O, Yildiz A, Topaloglu S, et al. Clinical features of isolated ventricular noncompaction in adults long-term clinical course, echocardiographic properties, and predictors of left ventricular failure. J Card Fail 2006;12:726-33. 24. Belanger AR, Miller MA, Donthireddi UR, Najovits AJ, Goldman ME. New classification scheme of left ventricular noncompaction and correlation with ventricular performance. Am J Cardiol 2008;102:92-6. 25. Fazio G, Novo G, Casalicchio C, Di Gesaro G, Sutera L, Grassedonio E, et al. Left ventricular non-compaction cardiomyopathy in children: is segmental fibrosis the cause of tissue Doppler alterations and of EF reduction? Int J Cardiol 2009;132:278-80. 26. Nucifora G, Aquaro GD, Pingitore A, Masci PG, Lombardi M. Myocardial fibrosis in isolated left ventricular non-compaction and its relation to disease severity. Eur J Heart Fail 2011;13:170-6. 27. Gebhard C, St€ahli BE, Greutmann M, Biaggi P, Jenni R, Tanner FC. Reduced left ventricular compacta thickness: a novel echocardiographic criterion for non-compaction cardiomyopathy. J Am Soc Echocardiogr 2012;25:1050-7. 28. Peters F, Khandheria BK, Libhaber E, Maharaj N, Dos Santos C, Matioda H, et al. Left ventricular twist in left ventricular noncompaction. Eur Heart J Cardiovasc Imaging 2014;15:48-55. 29. Captur G, Muthurangu V, Cook C, Flett AS, Wilson R, Barison A, et al. Quantification of left ventricular trabeculae using fractal analysis. J Cardiovasc Magn Reson 2013;15:36. 30. Thavendiranathan P, Dahiya A, Phelan D, Desai MY, Tang WH. Isolated left ventricular non-compaction controversies in diagnostic criteria, adverse outcomes and management. Heart 2013;99:681-9. http://dx.doi.org/10.1016/j.echo.2014.06.015
Beware of Life-Threatening Activation of Air Bubble Detector during Contrast Echocardiography in Patients on Venoarterial Extracorporeal Membrane Oxygenator Support To the Editor: Venoarterial extracorporeal membrane oxygenation (ECMO) is a temporizing therapy for patients with refractory cardiogenic shock, and it may also be a bridge to destination therapy or cardiac transplantation. Patients requiring venoarterial ECMO are, by definition, on the verge of cardiopulmonary collapse. Acute disruption of forward flow in ECMO-dependent patients will result in severe hypoperfusion and must be avoided at all costs.1 It is common practice to use contrast transthoracic echocardiography to improve the visualization of endocardial borders and allow more accurate assessments of ventricular function.2-4 This information is used clinically to determine whether to wean patients from ECMO support. The ECMO system used at our institution (CARDIOHELP; MAQUET Medical Systems USA, Wayne, NJ) has an integrated sensor that uses ultrasound to detect changes in flow dynamics associated with the presence of air bubbles or thrombi >5 mm in dimension. Activation of the bubble detector results in an alarm, followed by pump shutdown. If the alarm is not overridden within 6 sec, ‘‘zero-flow mode’’ is engaged. This mode applies sufficient revolutions per minute to prevent backflow from the arterial cannula into the venous cannula and prevents forward flow as well, hence the name zero-flow mode. This safety feature is designed to prevent deleterious cardiovascular and neurologic sequelae associated with air embolism during ECMO. Nevertheless, although this is a safety feature, stopping the ECMO circuitry and therefore the blood flow may be followed by deleterious consequences such as hypotension or the occurrence of thrombi.
echocardiographic examinations) in 2010 and 181 cases (1.0% of total echocardiographic examinations) in 2013. The pendulum swing raises a concern that we may have transitioned from under- to overdiagnosis as the result perhaps of arbitrary diagnostic criteria. DIAGNOSTIC CONUNDRUM Kohli et al.8 tested the echocardiographic criteria of Chin et al.,5 Jenni et al.,1 and St€ ollberger and Finsterer9 in patients with definitive LVNC. There was poor correlation among the three echocardiographic definitions, with only 30% of patients fulfilling all three criteria.8 Furthermore, Kohli et al. found that 8% of controls (four black subjects and one white subject) met at least one of the three criteria to diagnose LVNC. The review highlights the concern that the current echocardiographic criteria may be overly sensitive, particularly in black individuals, resulting in overdiagnosis of LVNC. This concern is further reified by a Mayo Clinic series in which 25% of patients with echocardiographic diagnoses of LVNC did not meet diagnostic criteria after careful retrospective review by two experts from the same echocardiography laboratory.10 This raises a serious concern of overdiagnosis (false positives) of LVNC in the practices of echocardiographic laboratories, with a negative impact of diagnosis on patients’ lives. Additional support for the diagnostic conundrum is the pathologic definition of LVNC as described by Burke et al.11 and Freedom et al.12 Freedom et al. described the unique anatomic features of hearts explanted from patients with LVNC. The hearts revealed a luminal meshwork of thin and thick endocardial bands, tendons, filaments, and trabeculations that intermixed to form a discrete trabecular layer of the LV wall to its apex. The thick and coarse trabeculations of the trabecular layer were separated by deep recesses. They did not use ratios to identify LVNC. Burke et al. described 14 explanted hearts with LVNC (nine of 14 sudden cardiac deaths). The pathologic definition included poorly developed papillary muscles and a noncompacted inner LV myocardial layer that comprised > 50% of the LV thickness. An important finding to note is that in four of 14 cases (27%), the noncompacted/compacted myocardial ratio was < 2. The statistic that 27% of patients with pathoanatomic diagnoses of LVNC did not meet an arbitrary cutoff ratio of noncompacted to compacted myocardium > 2 reinforces the limitation of diagnosing LVNC solely on the basis of measurements of ratios. We are at the precipice of a slippery slope of labeling people without a disease as having a serious disease entity. This is deja vu, because a similar chasm was scaled with asymmetric septal hypertrophy (ASH) and hypertrophic cardiomyopathy (HCM). The recognition that HCM could not be defined by diagnostic criteria using only measurements and an arbitrary ratio resulted in the withering of ASH as pathognomonic of HCM. Churchill’s quotation should resonate in our approach to obtain a deeper understanding of the LVNC spectrum. Lessons learned from a historical review of the measurements and ratios used to validate a diagnosis of HCM may prevent us from repeating the same errors. We present how the lesson of the experience with ASH and HCM could apply to LVNC.
HISTORICAL LESSONS: ASYMMETRIC SEPTAL HYPERTROPHY Four decades ago, in 1974, Henry and colleagues published their finding that ASH was a sensitive and specific disease marker of
Correspondence 1129
Journal of the American Society of Echocardiography Volume 27 Number 10
idiopathic hypertrophic subaortic stenosis. ASH was characterized by a ventricular septum that was $ 1.3 times as thick as the posterior LV free wall.13-15 They concluded that ASH was a pathognomonic anatomic abnormality of idiopathic hypertrophic subaortic stenosis.16 The observation that ASH was possible even with a normal thickness of the septum resulted in many normal individuals’ being incorrectly diagnosed with idiopathic hypertrophic subaortic stenosis (e.g., ventricular septum 12 mm, posterior wall 9 mm). With the introduction of two-dimensional echocardiography, the diseaseidentifying ratio went from ASH to disproportionate upper septal thickness. However, soon disproportionate upper septal thickness also was noted in systemic hypertension, pulmonary hypertension, valvular heart disease, and coarctation of the aorta.13 The lack of a true criterion standard, such as a genetic marker, to identify LVNC and its heterogeneous phenotypic expressions has inhibited our ability to determine a valid, reproducible definition. Furthermore, our inability to define whether a hypertrabeculated phenotype MLVNC/LVHT will transition to a cardiomyopathy complicates the issue. Thus, diagnosing the difference between the variant characterized by prominent apical trabeculations, MLVNC/LVHT, and MLVNC+D or MLVNC+H poses a new challenge to the medical community. A diagnostic modality ensuring a valid diagnosis of LVNC as reliably as a genetic marker has remained elusive. Measurement of not only morphologic features but also of advanced echocardiographic parameters, such as strain, strain rate, displacement, rotation, torsion, and deformation, currently has not achieved this dream.17-21 The main lesson learned from a temporal review of HCM that lends insight to the spectrum of LVNC is that disease should not be defined by measurements and ratios in isolation. Historically, the entity LVNC was described and studied in patients with abnormal systolic function. In 1990, Chin et al.5 described their echocardiographic findings in eight patients with isolated LVNC. Five of the eight patients had depressed LV systolic function. Jenni et al.1 in 2001 reviewed 34 adult patients with LVNC. Seven hearts were available for anatomic review through heart transplantation (three patients) or autopsy (four patients). LV ejection fractions ranged from 29% to 38% in these seven patients. A recent study in France reviewed the clinical and echocardiographic features of 105 patients with LVNC.22 Of these patients, 84% had reduced LV ejection fractions. These three studies reveal that the ratio-based criteria to diagnose LVNC were derived from diseased myopathic ventricles. We must not repeat the historical mistakes made with ASH and rely on an arbitrary ratio to diagnose HCM. Analysis must be multivariate to prevent under- and overdiagnosis. The diagnostic tools must have clinical application that is sensitive and specific to allow a distinction between normal anatomic variants, MLVNC/LVHT, and diseasestate MLVNC+D or MLVNC+H. BEYOND MEASUREMENTS AND RATIOS The present diagnostic tools result in uncertainty, as the noncompacted/compacted myocardial ratio has limitations, and the extent of noncompacted LV areas cannot distinguish with certainty disease from a variation of normal anatomy. Available studies have identified conflicting results: that the degree of LVNC is not related to the severity of LV systolic dysfunction23,24 and that the degree of LVNC is related to the degree of LV dysfunction.22,25 One study observed myocardial fibrosis in noncompacted and compacted myocardial segments with similar prevalence, supporting the theory that noncompacted myocardium is a phenotypic marker of an
underlying diffuse cardiomyopathy involving both noncompacted and compacted myocardium.26 These findings need further investigation and validation. Where do we go from here? Recent research suggests that maximal systolic compacta thickness < 8 mm is specific for LVNC, allowing differentiation from normal hearts and myocardial thickening due to pressure overload, and may be used as an additional diagnostic criteria.27 Peters et al.28 found that LV twist is diminished in subjects with LVNC and normal rotation. Rigid body rotation occurred in 53% of patients (32 of 60) with LVNC. Captur et al.29 identified that fractal analysis of trabeculations may aid in distinguishing healthy volunteers from patients with LVNC and that fractal dimension of trabeculations is greater in healthy blacks than whites. Despite these incremental advances, we are still left without a definitive way to diagnose LVNC. Current diagnostic criteria alone appear inadequate to make or refute the diagnosis of LVNC definitively.30 NEXT STEPS The search for more definitive diagnostic tools must continue with collaboration among large medical centers. There is a need for an LVNC consensus group to forge the path to a deeper understanding of this complex cardiomyopathy through international registries and multicenter collaboration. The collaboration must include the cross-pollination of ideas from the fields of embryology, genetics, and imaging. The use of a common nomenclature such as MOGE(S) will be advantageous. CONCLUSIONS Clearly, all present-day advances leave us wanting for a more sensitive and specific way of distinguishing MLVNC/LVHT from the disease state of LVNC cardiomyopathy. The interpretation and diagnosis must extend beyond measurements and ratios, as identified when we went from ASH to HCM. We must distinguish MLVNC/LVHT from MLVNC+D or MLVNC+H to prevent overdiagnosis. Ultimately, the genetic diagnosis of different types of HCM became a reality. Hopefully, the genetics of LVNC also will become a reality. The criteria finally chosen and accepted to diagnose LVNC must incorporate all aspects of MOGE(S). In daily practice, we must approach the diagnosis with broad clinical perspective. The judicious use of echocardiography and magnetic resonance imaging by thoughtful clinicians should allow accurate diagnosis, appropriate follow-up, and prognostication. When the cardiomyopathy is identified, we must follow patients carefully for heart failure, rhythm disturbances, and neurologic symptoms. When M LVNC/LVHT is identified, we need surveillance with echocardiography to determine if there is transition to the cardiomyopathy. As Churchill so eloquently advised, we must learn from history to avoid repeating the same error in the diagnosis of LVNC using a ratio (noncompacted/compacted myocardium > 2.0) that was made with HCM using ASH (ventricular septum/ posterior wall > 1.3) as a ratio.
Timothy E. Paterick, MD, JD A. Jamil Tajik, MD Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke’s Medical Centers, University of Wisconsin School of Medicine and Public Health, Milwaukee, Wisconsin
1130 Correspondence
REFERENCES 1. 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. 2. Wessels A, Sedmera D. Developmental anatomy of the heart: a tale of mice and man. Physiol Genomics 2003;15:165-76. 3. Paterick TE, Gerber TC, Pradhan SR, Lindor NM, Tajik AJ. Left ventricular noncompaction cardiomyopathy: what do we know? Rev Cardiovasc Med 2010;11:92-9. 4. Arbustini E, Narula N, Dec GW, Reddy KS, Greenberg B, Kushwaha S, et al. The MOGE(S) classification for a phenotype-genotype nomenclature of cardiomyopathy: endorsed by the World Heart Federation. J Am Coll Cardiol 2013;62:2046-72. 5. 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. 6. St€ ollberger C, Finsterer J, Blazek G. Left ventricular hypertrabeculation/noncompaction and association with additional cardiac abnormalities and neuromuscular disorders. Am J Cardiol 2002;90: 899-902. 7. Paterick TE, Umland MM, Jan MF, Ammar KA, Kramer C, Khandheria BK, et al. Left ventricular noncompaction: a 25-year odyssey. J Am Soc Echocardiogr 2012;25:363-75. 8. Kohli SK, Pantazis AA, Shah JS, Adeyemi B, Jackson G, McKenna WJ, et al. Diagnosis of left-ventricular non-compaction in patients with leftventricular systolic dysfunction: time for a reappraisal of diagnostic criteria? Eur Heart J 2008;29:89-95. 9. St€ ollberger C, Finsterer J. Left ventricular hypertrabeculation/noncompaction. J Am Soc Echocardiogr 2004;17:91-100. 10. Stanton C, Bruce C, Connolly H, Brady P, Syed I, Hodge D, et al. Isolated left ventricular noncompaction syndrome. Am J Cardiol 2009;104: 1135-8. 11. Burke A, Mont E, Kutys R, Virmani R. Left ventricular noncompaction: a pathological study of 14 cases. Hum Pathol 2005;36:403-11. 12. Freedom RM, Yoo SJ, Perrin D, Taylor G, Petersen S, Anderson RH. The morphological spectrum of ventricular noncompaction. Cardiol Young 2005;15:345-64. 13. Kansal S, Roitman D, Sheffield LT. Interventricular septal thickness and left ventricular hypertrophy. An echocardiographic study. Circulation 1979; 60:1058-65. 14. Epstein SE, Henry WL, Clark CE, Roberts WC, Maron BJ, Ferrans VJ, et al. Asymmetric septal hypertrophy. Ann Intern Med 1974;81:650-80. 15. Williams LK, Frenneaux MP, Steeds RP. Echocardiography in hypertrophic cardiomyopathy diagnosis, prognosis, and role in management. Eur J Echocardiogr 2009;10:iii9-14. 16. Henry WL, Clark CE, Epstein SE. Asymmetric septal hypertrophy. Echocardiographic identification of the pathognomonic anatomic abnormality of IHSS. Circulation 1973;47:225-33. 17. Paterick TE, Tajik AJ. Left ventricular noncompaction. Circ J 2012;76: 1556-62. 18. St€ ollberger C, Gerecke B, Finsterer J, Engberding R. Refinement of echocardiographic criteria for left ventricular noncompaction. Int J Cardiol 2013;165:463-7. 19. Willemsen HM, van den Berg MP. A few more pieces in the puzzle of noncompaction cardiomyopathy. Eur J Heart Fail 2011;13:127-9. 20. Attenhofer Jost CH, Connolly HM. Left ventricular non-compaction: dreaming of the perfect diagnostic tool. Eur J Heart Fail 2012;14:113-4. 21. Peters F, Khandheria BK. Isolated left ventricular noncompaction: what do we really know? Curr Cardiol Rep 2012;14:381-8. 22. Habib G, Charron P, Eicher JC, Giorgi R, Donal E, Laperche T, et al. Isolated left ventricular non-compaction in adults: clinical and echocardiographic features in 105 patients. Results from a French registry. Eur J Heart Fail 2011;13:177-85.
Journal of the American Society of Echocardiography October 2014
23. Aras D, Tufekcioglu O, Ergun K, Ozeke O, Yildiz A, Topaloglu S, et al. Clinical features of isolated ventricular noncompaction in adults long-term clinical course, echocardiographic properties, and predictors of left ventricular failure. J Card Fail 2006;12:726-33. 24. Belanger AR, Miller MA, Donthireddi UR, Najovits AJ, Goldman ME. New classification scheme of left ventricular noncompaction and correlation with ventricular performance. Am J Cardiol 2008;102:92-6. 25. Fazio G, Novo G, Casalicchio C, Di Gesaro G, Sutera L, Grassedonio E, et al. Left ventricular non-compaction cardiomyopathy in children: is segmental fibrosis the cause of tissue Doppler alterations and of EF reduction? Int J Cardiol 2009;132:278-80. 26. Nucifora G, Aquaro GD, Pingitore A, Masci PG, Lombardi M. Myocardial fibrosis in isolated left ventricular non-compaction and its relation to disease severity. Eur J Heart Fail 2011;13:170-6. 27. Gebhard C, St€ahli BE, Greutmann M, Biaggi P, Jenni R, Tanner FC. Reduced left ventricular compacta thickness: a novel echocardiographic criterion for non-compaction cardiomyopathy. J Am Soc Echocardiogr 2012;25:1050-7. 28. Peters F, Khandheria BK, Libhaber E, Maharaj N, Dos Santos C, Matioda H, et al. Left ventricular twist in left ventricular noncompaction. Eur Heart J Cardiovasc Imaging 2014;15:48-55. 29. Captur G, Muthurangu V, Cook C, Flett AS, Wilson R, Barison A, et al. Quantification of left ventricular trabeculae using fractal analysis. J Cardiovasc Magn Reson 2013;15:36. 30. Thavendiranathan P, Dahiya A, Phelan D, Desai MY, Tang WH. Isolated left ventricular non-compaction controversies in diagnostic criteria, adverse outcomes and management. Heart 2013;99:681-9. http://dx.doi.org/10.1016/j.echo.2014.06.015
Beware of Life-Threatening Activation of Air Bubble Detector during Contrast Echocardiography in Patients on Venoarterial Extracorporeal Membrane Oxygenator Support To the Editor: Venoarterial extracorporeal membrane oxygenation (ECMO) is a temporizing therapy for patients with refractory cardiogenic shock, and it may also be a bridge to destination therapy or cardiac transplantation. Patients requiring venoarterial ECMO are, by definition, on the verge of cardiopulmonary collapse. Acute disruption of forward flow in ECMO-dependent patients will result in severe hypoperfusion and must be avoided at all costs.1 It is common practice to use contrast transthoracic echocardiography to improve the visualization of endocardial borders and allow more accurate assessments of ventricular function.2-4 This information is used clinically to determine whether to wean patients from ECMO support. The ECMO system used at our institution (CARDIOHELP; MAQUET Medical Systems USA, Wayne, NJ) has an integrated sensor that uses ultrasound to detect changes in flow dynamics associated with the presence of air bubbles or thrombi >5 mm in dimension. Activation of the bubble detector results in an alarm, followed by pump shutdown. If the alarm is not overridden within 6 sec, ‘‘zero-flow mode’’ is engaged. This mode applies sufficient revolutions per minute to prevent backflow from the arterial cannula into the venous cannula and prevents forward flow as well, hence the name zero-flow mode. This safety feature is designed to prevent deleterious cardiovascular and neurologic sequelae associated with air embolism during ECMO. Nevertheless, although this is a safety feature, stopping the ECMO circuitry and therefore the blood flow may be followed by deleterious consequences such as hypotension or the occurrence of thrombi.
