Original Article
Noncompaction cardiomyopathy: Manifestation as a surgical pitfall – rare but real
Asian Cardiovascular & Thoracic Annals 2015, Vol. 23(2) 133–139 ß The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492314533559 aan.sagepub.com
Supreet P Marathe1, Pradeep Vaideeswar2, Roneil Parikh3, Prashant Mishra1, Balaji Aironi1, Nandkishor B Agrawal1 and Arivarsan Karunamurthy2
Abstract Objectives: Noncompaction cardiomyopathy is characterized by hyper-trabeculation of the myocardium. The patients present with heart failure and variable combination of arrhythmias and thromboembolism. Although several articles have shed light on the medical aspect of this disease, none have highlighted its surgical relevance. A death following ligation of a patent ductus arteriosus prompted us to evaluate the surgical aspects of this disease. Methods: Autopsy records from 2003 to 2012 were reviewed, and cases identified as noncompaction cardiomyopathy were retrieved and analyzed. Cases with obligatory hyper-trabeculation were excluded. Results: Thirteen patients were found to have noncompaction cardiomyopathy in 9427 autopsies performed. Their ages ranged from 4 months to 55 years; 10 were children, and all 3 adults were over 45 years of age. Only one patient had an antemortem diagnosis of noncompaction cardiomyopathy on echocardiography. There were 7 postoperative deaths. Conclusions: Although noncompaction cardiomyopathy is rare, missing its diagnosis in a patient operated on for another indication can spell disaster postoperatively. As the clinical picture is nonspecific and the disease is not very well known, it needs vigilance on the part of the echocardiographer and surgeon.
Keywords Cardiomyopathies, Heart failure, Isolated noncompaction of the ventricular myocardium, Postoperative complications, Ventricular dysfunction, left
Introduction Cardiomyopathies are more or less restricted to the domain of cardiology for the management of refractory cardiac failure and/or rhythm disorders. Cardiac surgeons encounter cardiomyopathies usually for surgical resection of endomyocardium or valves, or for the ultimate treatment of failure by heart transplantation. Noncompaction cardiomyopathy (NCC) is a rare and relatively young cardiomyopathy that continues to be relegated to the unclassifiable category of cardiomyopathies.1 The term noncompaction was first used by Chin and colleagues2 in 1990, although the echocardiographic description was made by Engberding and Bender3 in 1984, as ‘‘persistence of isolated myocardial sinusoids’’. It is characterized by a marked trabecular meshwork and deep inter-trabecular recesses, especially
in the left ventricle, and not surprisingly, most patients present with cardiac failure. In a cardiac surgical scenario, albeit rare, NCC can be a surgical pitfall because lack of awareness or nonrecognition of this disorder can spell doom for the patient postoperatively. Although many large series have elaborated the medical
1 PK Sen Department of Cardiovascular and Thoracic Surgery, Seth GS Medical College and KEM Hospital, Mumbai, India 2 Department of Pathology, Seth GS Medical College, Mumbai, India 3 Seth GS Medical College, Mumbai, India
Corresponding author: Pradeep Vaideeswar, Department of Pathology (Cardiovascular & Thoracic Division), Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012, India. Email: [email protected]
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aspects of this disease,4,5 it is time to recognize its surgical relevance.
Patients and methods Case study A 4-month-old female was referred to our institute with recurrent respiratory tract infections and failure to thrive. She was diagnosed as a case of atrioventricular septal defect with heart block (atrial and ventricular rates of 120 and 90 beats per minute, respectively) by foetal ultrasonography at 30 weeks’ gestation. The mother was followed up with a normal delivery at term. The baby had a 10-day stay in the neonatal intensive care unit; the details were, however, not available. Her course was uneventful until the age of 2 months when she developed recurrent respiratory tract infections. Two-dimensional transthoracic echocardiography revealed a large (5 mm) patent ductus arteriosus with a left-to-right shunt, and the possibility of left ventricular noncompaction (Figure 1). There was no evidence of atrioventricular septal defect. Complete heart block was seen on an electrocardiogram, with an escape rate of 70 per minute, but there was no history or evidence of any symptoms associated with bradycardia. After a routine work-up, the patient underwent elective patent ductus arteriosus ligation 8 days after admission; transvenous pacing and epicardial pacing leads were kept on standby. The procedure was
uneventful. She had a good escape rate intraoperatively. Hemodynamics were maintained without any inotropics. Extubation was attempted 2 h later, but she had to be immediately reintubated due to worsening hemodynamics and respiratory compromise. Echocardiography revealed a ligated ductus with poor left ventricular function. She could not be weaned off the ventilator and had multiple episodes of bradycardia and hypotension on the 3rd postoperative day. Transvenous pacing was undertaken. However, in spite of her adequate heart rate, she was unable to maintain blood pressure with serially worsening cardiac failure, rising central venous pressure, and need for higher doses of inotropics, culminating in cardiac arrest. A restricted autopsy (partial chest) was performed. The heart (weight 80 g) was markedly enlarged with moderate biventricular enlargement (Figure 2A). The great arteries had a normal relationship with dilatation of the pulmonary trunk and its branches. The ductus had been ligated. There were no interatrial or interventricular communications. Interestingly, the middle and apical thirds of the left ventricular myocardium appeared hyper-trabeculated (Figure 2B), which was best seen on transverse section (Figure 2C). This morphology satisfied one of the criteria of Jenni and colleagues6 for NCC: the ratio of the much thicker noncompacted endocardial layer to the thin compacted epicardial layer was greater than 2.0. Histology revealed prominent trabeculae covered by a thick endocardium with focal myocytolyses of the subendocardial fibres
Figure 1. Echocardiogram in apical 4-chamber view showing noncompaction of the left ventricle (LV). LA: left atrium; RA: right atrium; RV: right ventricle.
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Figure 2. (A) Moderate cardiomegaly with biventricular enlargement. Sutures can be seen at the ligated ductus. AA: ascending aorta; LAA: left atrial appendage; LV: left ventricle; PT; pulmonary trunk; RAA: right atrial appendage; RV: right ventricle. (B) A prominent trabecular meshwork is seen in the mid-portion and apical aspect of the left ventricle (LV). CS: coronary sinus; LA: left atrium; MV: mitral valve. (C) Noncompaction is well appreciated on transverse section through a mid-portion of the ventricles. LV: left ventricle; RV: right ventricle. (D) The trabeculae are lined by thickened endocardium (hematoxylin and eosin stain, original magnification 250).
(Figure 2D). This course of events prompted us to review our autopsy records for the past 10 years. Autopsy records from the cardiovascular and thoracic division of the department of pathology for a period of 10 years (2003 to 2012) were reviewed, and cases identified and indexed as NCC were retrieved for analysis. Our hospital is a tertiary care center with an out-patient load of 1.8 million and admissions of 78,000 annually; the autopsy rate is approximately 15% of all hospital deaths. The patient demographics, clinical presentation, investigations, details of cardiac surgery, and postoperative course were noted. All hearts had been cut as per the flow of blood and described in detail. NCC was classified as isolated lesions or
nonisolated when associated with other cardiac anomalies. Cases in which hyper-trabeculation was obligatory, as in hypoplastic right or left ventricular syndromes, were excluded.
Results In a span of 10 years, 13 cases were diagnosed as NCC among 9427 autopsies performed, giving an incidence of 0.14%. There were 6 males and 7 females with an age range of 4 months to 55 years (mean 12 years and 7 months). The clinical details are given in Tables 1 and 2. Ten were children, 6 (60%) of whom (including the case described above) had a coexisting congenital
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Table 1. Patients with noncompaction cardiomyopathy who underwent surgery. Case no.
Age/sex
Preoperative diagnosis
Surgery
Cause of death
1
4 months/F
PDA ligation
Refractory cardiac failure þ NCC
2 3. 4 5 6 7
5 months/M 1 year/F 1 year/F 1 year/M 46 years/F 55 years/M
PDA þ left-to-right shunt, CHB, moderate PH, NCC Mid-muscular VSD, severe PH, LVH Perimembranous VSD, severe PH, LVH Moderate ASD, Swiss-cheese VSD Tricuspid atresia Type 1c Rheumatic calcified mitral stenosis IHD, ejection fraction 60%
ICR of VSD ICR of VSD ICR of VSD, ASD PA banding MVR CABG
Refractory cardiac failure þ NCC Refractory cardiac failure þ NCC Pneumonia þ NCC Refractory cardiac failure þ NCC Refractory cardiac failure þ NCC Pulmonary thromboembolism þ NCC
ASD: atrial septal defect; CABG: coronary artery bypass grafting; CHB: complete heart block; ICR: intracardiac repair; IHD: ischemic heart disease; LVH: left ventricular hypertrophy; MVR: mitral valve replacement; NCC: noncompaction cardiomyopathy; PA: pulmonary artery; PDA: patent ductus arteriosus; PH: pulmonary hypertension; VSD: ventricular septal defect.
Table 2. Patients with noncompaction cardiomyopathy who did not have surgery. Case no.
Age/sex
Primary diagnosis
Cause of death
8 9 10 11 12 13
5 months/M 6 months/M 1.5 years/F 2 years/F 11 years/F 45 years/M
Viral myocarditis, EF 30% Large PDA (4 mm) Myocarditis, EF 15% Lower RTI þ CHD Rheumatic MR þ AF IHD, EF 15%–20%
Refractory cardiac failure þ NCC Refractory cardiac failure þ NCC Refractory cardiac failure þ NCC VSD, PS, refractory failure þ NCC Anaphylactic shock after benzathine/penicillin þ NCC Refractory cardiac failure þ NCC
AF: atrial fibrillation; CHD: congenital heart disease; EF: ejection fraction; IHD: ischemic heart disease; MR: mitral regurgitation; NCC: noncompaction cardiomyopathy; PDA: patent ductus arteriosus; PS: pulmonary stenosis; RTI: respiratory tract infection; VSD: ventricular septal defect.
7 cases operated on, 5 had a similar postoperative course with inability to wean off the ventilator and/or support, eventually culminating in failure and death. In all postoperative cases, surgical causes of failure such as inadequate repair or patch dehiscence (for septal defects) had been ruled out by echocardiography. In the isolated and nonisolated groups, the deep inter-trabecular recesses communicated with the cavity of the left ventricle but not with the coronary arterial circulation.
Discussion Figure 3. Transverse slice through the ventricles shows noncompaction of right ventricle (RV) and left ventricle (LV). The arrow points to a small trabecular muscular ventricular septal defect.
cardiac anomaly (Figure 3); the others had a clinical diagnosis of myocarditis or rheumatic heart disease (Figure 4). A family history of sudden death in a sibling was present in case no. 10. The other 3 patients were adults, all over 45 years of age, and were affected by either rheumatic or ischemic heart disease. Only one patient (case no. 1) had a diagnosis of NCC. Of the
Developmentally, the myocardium is a loose meshwork of trabeculae. Rearrangement of myofibers and coalescence of inter-trabecular spaces or recesses results in compaction or solidification of the myocardium. This phenomenon, which is important for the function of the heart as an effective pump, occurs between 5 to 8 weeks of gestation; NCC is said to result from arrest of this process. This morphology simulates reptilian heart which is made up entirely of non-compacted myocardium with sinusoids directly channelling blood from ventricular lumen to the myocardium. The non-compacted hearts are hence called snake or spongy hearts,
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Figure 4. (A) The opened out left ventricular (LV) inflow tract showing dilatation of the mitral valve annulus (MV). The anterior papillary muscle (APM) and posterior papillary muscle (PPM) are attenuated and flush with the endocardial surface of the LV. Note the rounding of the free margins of valve leaflets and reduced number of tendinous cords. (B, C) Hyper-trabeculations of the mid portion and apical third of the LV as seen from the inflow aspect, and (D) well brought out on transverse sections.
an appearance noted as early as 1926 by Grant.7 However, it is advocated to use the term noncompaction, and terms such as persistent sinusoids or hyper-trabeculation should be avoided in the light of developmental and evolutionary considerations.8 NCC is a genetically heterogeneous disorder linked to mutations of sarcomeric and non-sarcomeric proteins, and it occurs in sporadic as well as familial forms.9 Despite such advances, it remains an unclassified cardiomyopathy,1 although the American Heart Association has classified it as primary genetic cardiomyopathy.10 NCC can present in isolation or in combination with other congenital heart diseases or inherited systemic disorders. However, follow-up of patients with associated congenital heart disease has not been performed to evaluate the surgical outcome. In our series, 7 of 13 patients had an associated cardiac anomaly, but none had a demonstrable extracardiac disease. Although absence of coexisting congenital heart diseases is taken as a criterion for noncompaction, it should not be so, due to the clinical implications.6 The time of arrest of the process of compaction determines the degree and extent of noncompaction.11 The left ventricle and its apex are the last parts of the heart to undergo compaction. Consequently, the left ventricle is the most common chamber affected.
Furthermore, the cardiomyopathy may involve one or more of the 9 segments of the left ventricle (apical, 4 mid-ventricular, and 4 basal segments with an anterior, septal, lateral, and inferior segment each).12 The apex is always involved in NCC, as noted in all of our cases. Although right ventricular noncompaction has been described and reported,13,14 because it is extremely difficult to differentiate between a heavily trabeculated right ventricle and non-compacted myocardium, its true existence is controversial.4 The true prevalence of NCC is currently unclear. It is possible that before the advent of modern-day diagnostic imaging, noncompaction existed but was never diagnosed antemortem, or more often misdiagnosed. A recent rise in reports of NCC indicates an evolving awareness of the disease. The diagnosis is best established by echocardiography and/or magnetic resonance imaging;2,6,15,16 its prevalence in echocardiographic series varies from 0.014% to 1.3%.4,5,17 Our study revealed an incidence of 0.14% among the autopsied cases, but this may not be representative of the true prevalence of the disease. Three of the patients were adults and the other 10 were children. In the pediatric population, NCC is the third most common type of primary cardiomyopathy, after dilated and hypertrophic cardiomyopathy.18 The functional implication
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of the abnormal myocardium such as increased myocardial fibrosis can be assessed using newer techniques.19 Apart from moderate to marked endocardial fibrosis and subendocardial ischemia, myocardial fibrosis was not seen in any of these cases; regional fibrosis was present in adult patients with ischemic heart disease. The clinical features are extremely variable. The patient can remain asymptomatic for decades only to be decompensated by stress, or NCC can present with overt symptoms in the first few years of life, usually in the form of heart failure, conduction abnormalities, or embolic events, no different from the more frequent dilated cardiomyopathy.2 Although diagnostic echocardiographic and magnetic resonance imaging criteria have distinct cutoffs, the symptomatology may not be equivalent, resulting in a clinical-radiological mismatch. Hence we can have a patient with subtle heart failure but falling short of the diagnostic criteria, as well as an asymptomatic patient fulfilling the diagnostic criteria. Further, echocardiography is operatordependent. The experience of the echocardiographer can definitely affect missed noncompaction. Existing diagnostic criteria have also been questioned, and the right measurements have to be taken in the right view and in the right phase of the cardiac cycle.20 Although cardiac magnetic resonance imaging is useful to confirm the diagnosis of noncompaction complementary to echocardiography, it does not form part of the standard work-up for a cardiac patient. Such problems are magnified when the patients first undergo heart surgery. To our knowledge, no series has analyzed postoperative patients with coexisting NCC. In our series, only one patient was diagnosed conclusively with noncompaction on echocardiography. The varied clinical presentation gives yet another reason to miss the diagnosis. Symptoms and signs are more likely to be attributed to the primary cardiac disease (congenital or acquired) needing surgery, rather than to noncompaction. The 3 cases of isolated NCC were diagnosed as myocarditis or rheumatic mitral regurgitation. As the clinical presentation is varied, treatment is symptom-directed, predominantly involving management of heart failure. Arrhythmias need pacing devices. Thromboembolic episodes demand anticoagulation, or prophylactic anticoagulation is indicated in patients without such episodes but with rhythm disturbances. Heart transplantation has been described as a successful modality for the ultimate treatment of noncompaction. As modern day cardiac surgery strives for perfection, no stone should be left unturned to prevent morbidity and mortality. It is time to recognize noncompaction as an entity with surgical implications. We hypothesize that failure of the myocardium as an effective pump
resulted in the detrimental postoperative courses of our patients in the form of refractory failure, the noncompaction being unmasked due to perioperative stress. Hence even considering the diagnosis during an unexpected postoperative recovery can be helpful to cope with the problem and the likely prognosis. A clinical triad of heart failure, arrhythmias, and thromboembolic events should lead to a strong suspicion of noncompaction, especially with the coexistence of other congenital anomalies, muscle dystrophies, mitochondrial myopathies, or neuropathies, but no conclusive syndromes have been proven due to the small number of cases. As missing noncompaction is not impossible, screening for it should be part of the standard protocol. Because views and measurements are specific, even a possibility should prompt further evaluation. Clinical findings of myocarditis, unexplained low ejection fraction, recurrent congestive heart failure, or dilated cardiomyopathy are worth considering as noncompaction until proven otherwise, at least in the pediatric population. Family screening and genetic screening should be carried out in case there is history of cardiomyopathy. It is worth reiterating that even a diagnosis of dilated or hypertrophic cardiomyopathy in a relative may actually be noncompaction. For the surgeon, diagnosing a patient needing cardiac surgery as having noncompaction increases the possible postoperative complications exponentially, as we experienced in our case of patent ductus arteriosus ligation. It is also possible that the patient can have an absolutely uneventful recovery, reflecting the clinical spectrum of the disease. When surgery is inevitable, discussion with the family of the possible implications and weighing the potential risks and benefits of surgery is necessary. Ventricular assist devices and extracorporeal membrane oxygenation should be a part of the surgical armamentarium. As our study was an autopsy review, the incidence of noncompaction may not be indicative of the actual prevalence of the disease. Because not all deaths undergo autopsies and clinicians would be more likely to opt for an autopsy when the cause of death is unclear, there may be a selection bias. The clinical profile of the 13 patients was extremely heterogeneous, thus there could be several confounding factors coming into play which could have affected outcomes. Although all other obvious causes were ruled out, there can be no way to definitely say that the cause of death was noncompaction although we are sure that it significantly affected the outcome. Our study highlights the need for strict clinical vigilance to diagnose noncompaction. Existing diagnostic criteria need reappraisal to include cases of noncompaction associated with other congenital anomalies. Further, no definitive guidelines exist when a patient
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with noncompaction faces surgery, hence more studies are needed to reveal the surgical impact of this disease. Funding This research received no specific grant from any funding agency in the public, commerical, or not-for-profit sectors.
Conflict of interest statement None declared.
References 1. Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2008; 29: 270–276. 2. Chin TK, Perloff JK, Williams RG, Jue K and Mohrmann R. Isolated noncompaction of left ventricular myocardium. A study of eight cases. Circulation 1990; 82: 507–513. 3. Engberding R and Bender F. Identification of a rare congenital anomaly of the myocardium by two-dimensional echocardiography: persistence of isolated myocardial sinusoids. Am J Cardiol 1984; 53: 1733–1734. 4. Oechslin EN, Attenhofer Jost CH, Rojas JR, Kaufmann PA and 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. 5. Aras D, Tufekcioglu O, Ergun K, 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: 726–733. 6. Jenni R, Goebel N, Tartini R, Schneider J, Arbenz U and Oelz O. Persisting myocardial sinusoids of both ventricles as an isolated anomaly: echocardiographic, angiographic, and pathologic anatomical findings. Cardiovasc Intervent Radiol 1986; 9: 127–131. 7. Grant RT. An unusual anomaly of the coronary vessels in the malformed heart of a child. Heart 1926; 13: 273–283. 8. Oechslin E and Jenni R. Left ventricular non-compaction revisited: a distinct phenotype with genetic heterogeneity? Eur Heart J 2011; 32: 1446–1456. 9. Sen-Chowdhry S and McKenna WJ. Left ventricular noncompaction and cardiomyopathy: cause, contributor, or epiphenomenon? Curr Opin Cardiol 2008; 23: 171–175.
10. Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006; 113: 1807–1816. 11. Sedmera D, Pexieder T, Vuillemin M, Thompson RP and Anderson RH. Developmental patterning of the myocardium. Anat Rec 2000; 258: 319–337. 12. Jenni R, Oechslin EN and van der Loo B. Isolated ventricular non-compaction of the myocardium in adults. Heart 2007; 93: 11–15. 13. Cavusoglu Y, Ata N, Timuralp B, et al. Noncompaction of the ventricular myocardium: report of two cases with bicuspid aortic valve demonstrating poor prognosis and with prominent right ventricular involvement. Echocardiography 2003; 20: 379–383. 14. Ying ZQ, Xu G, Chen S, Ma J and You XD. Cerebral infarction in an adult patient with right ventricular hypertrabeculation/noncompaction. Int J Cardiol 2008; 127: e150–e151. 15. Petersen SE, Selvanayagam JB, Wiesmann F, et al. Left ventricular non-compaction: insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol 2005; 46: 101–115. 16. Jacquier A, Thuny F, Jop B, et al. Measurement of trabeculated left ventricular mass using cardiac magnetic resonance imaging in the diagnosis of left ventricular non-compaction. Eur Heart J 2010; 31: 1098–1104. 17. Pignatelli RH, McMahon CJ, Dreyer WJ, et al. Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy. Circulation 2003; 108: 2672–2678. 18. Engberding R, Sto¨llberger C, Ong P, Yelbuz TM, Gerecke BJ and Breithardt G. Isolated non-compaction cardiomyopathy. Dtsch Arztebl Int 2010; 107: 206–213. 19. Nucifora G, Aquaro GD, Pingitore A, Masci PG and Lombardi M. Myocardial fibrosis in isolated left ventricular non-compaction and its relation to disease severity. Eur J Heart Fail 2011; 13: 170–176. 20. Kohli SK, Pantazis AA, Shah JS, et al. Diagnosis of left ventricular non-compaction in patients with left-ventricular systolic dysfunction: time for a reappraisal of diagnostic criteria? Eur Heart J 2008; 29: 89–95.
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Noncompaction cardiomyopathy: Manifestation as a surgical pitfall – rare but real
Asian Cardiovascular & Thoracic Annals 2015, Vol. 23(2) 133–139 ß The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492314533559 aan.sagepub.com
Supreet P Marathe1, Pradeep Vaideeswar2, Roneil Parikh3, Prashant Mishra1, Balaji Aironi1, Nandkishor B Agrawal1 and Arivarsan Karunamurthy2
Abstract Objectives: Noncompaction cardiomyopathy is characterized by hyper-trabeculation of the myocardium. The patients present with heart failure and variable combination of arrhythmias and thromboembolism. Although several articles have shed light on the medical aspect of this disease, none have highlighted its surgical relevance. A death following ligation of a patent ductus arteriosus prompted us to evaluate the surgical aspects of this disease. Methods: Autopsy records from 2003 to 2012 were reviewed, and cases identified as noncompaction cardiomyopathy were retrieved and analyzed. Cases with obligatory hyper-trabeculation were excluded. Results: Thirteen patients were found to have noncompaction cardiomyopathy in 9427 autopsies performed. Their ages ranged from 4 months to 55 years; 10 were children, and all 3 adults were over 45 years of age. Only one patient had an antemortem diagnosis of noncompaction cardiomyopathy on echocardiography. There were 7 postoperative deaths. Conclusions: Although noncompaction cardiomyopathy is rare, missing its diagnosis in a patient operated on for another indication can spell disaster postoperatively. As the clinical picture is nonspecific and the disease is not very well known, it needs vigilance on the part of the echocardiographer and surgeon.
Keywords Cardiomyopathies, Heart failure, Isolated noncompaction of the ventricular myocardium, Postoperative complications, Ventricular dysfunction, left
Introduction Cardiomyopathies are more or less restricted to the domain of cardiology for the management of refractory cardiac failure and/or rhythm disorders. Cardiac surgeons encounter cardiomyopathies usually for surgical resection of endomyocardium or valves, or for the ultimate treatment of failure by heart transplantation. Noncompaction cardiomyopathy (NCC) is a rare and relatively young cardiomyopathy that continues to be relegated to the unclassifiable category of cardiomyopathies.1 The term noncompaction was first used by Chin and colleagues2 in 1990, although the echocardiographic description was made by Engberding and Bender3 in 1984, as ‘‘persistence of isolated myocardial sinusoids’’. It is characterized by a marked trabecular meshwork and deep inter-trabecular recesses, especially
in the left ventricle, and not surprisingly, most patients present with cardiac failure. In a cardiac surgical scenario, albeit rare, NCC can be a surgical pitfall because lack of awareness or nonrecognition of this disorder can spell doom for the patient postoperatively. Although many large series have elaborated the medical
1 PK Sen Department of Cardiovascular and Thoracic Surgery, Seth GS Medical College and KEM Hospital, Mumbai, India 2 Department of Pathology, Seth GS Medical College, Mumbai, India 3 Seth GS Medical College, Mumbai, India
Corresponding author: Pradeep Vaideeswar, Department of Pathology (Cardiovascular & Thoracic Division), Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012, India. Email: [email protected]
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aspects of this disease,4,5 it is time to recognize its surgical relevance.
Patients and methods Case study A 4-month-old female was referred to our institute with recurrent respiratory tract infections and failure to thrive. She was diagnosed as a case of atrioventricular septal defect with heart block (atrial and ventricular rates of 120 and 90 beats per minute, respectively) by foetal ultrasonography at 30 weeks’ gestation. The mother was followed up with a normal delivery at term. The baby had a 10-day stay in the neonatal intensive care unit; the details were, however, not available. Her course was uneventful until the age of 2 months when she developed recurrent respiratory tract infections. Two-dimensional transthoracic echocardiography revealed a large (5 mm) patent ductus arteriosus with a left-to-right shunt, and the possibility of left ventricular noncompaction (Figure 1). There was no evidence of atrioventricular septal defect. Complete heart block was seen on an electrocardiogram, with an escape rate of 70 per minute, but there was no history or evidence of any symptoms associated with bradycardia. After a routine work-up, the patient underwent elective patent ductus arteriosus ligation 8 days after admission; transvenous pacing and epicardial pacing leads were kept on standby. The procedure was
uneventful. She had a good escape rate intraoperatively. Hemodynamics were maintained without any inotropics. Extubation was attempted 2 h later, but she had to be immediately reintubated due to worsening hemodynamics and respiratory compromise. Echocardiography revealed a ligated ductus with poor left ventricular function. She could not be weaned off the ventilator and had multiple episodes of bradycardia and hypotension on the 3rd postoperative day. Transvenous pacing was undertaken. However, in spite of her adequate heart rate, she was unable to maintain blood pressure with serially worsening cardiac failure, rising central venous pressure, and need for higher doses of inotropics, culminating in cardiac arrest. A restricted autopsy (partial chest) was performed. The heart (weight 80 g) was markedly enlarged with moderate biventricular enlargement (Figure 2A). The great arteries had a normal relationship with dilatation of the pulmonary trunk and its branches. The ductus had been ligated. There were no interatrial or interventricular communications. Interestingly, the middle and apical thirds of the left ventricular myocardium appeared hyper-trabeculated (Figure 2B), which was best seen on transverse section (Figure 2C). This morphology satisfied one of the criteria of Jenni and colleagues6 for NCC: the ratio of the much thicker noncompacted endocardial layer to the thin compacted epicardial layer was greater than 2.0. Histology revealed prominent trabeculae covered by a thick endocardium with focal myocytolyses of the subendocardial fibres
Figure 1. Echocardiogram in apical 4-chamber view showing noncompaction of the left ventricle (LV). LA: left atrium; RA: right atrium; RV: right ventricle.
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Figure 2. (A) Moderate cardiomegaly with biventricular enlargement. Sutures can be seen at the ligated ductus. AA: ascending aorta; LAA: left atrial appendage; LV: left ventricle; PT; pulmonary trunk; RAA: right atrial appendage; RV: right ventricle. (B) A prominent trabecular meshwork is seen in the mid-portion and apical aspect of the left ventricle (LV). CS: coronary sinus; LA: left atrium; MV: mitral valve. (C) Noncompaction is well appreciated on transverse section through a mid-portion of the ventricles. LV: left ventricle; RV: right ventricle. (D) The trabeculae are lined by thickened endocardium (hematoxylin and eosin stain, original magnification 250).
(Figure 2D). This course of events prompted us to review our autopsy records for the past 10 years. Autopsy records from the cardiovascular and thoracic division of the department of pathology for a period of 10 years (2003 to 2012) were reviewed, and cases identified and indexed as NCC were retrieved for analysis. Our hospital is a tertiary care center with an out-patient load of 1.8 million and admissions of 78,000 annually; the autopsy rate is approximately 15% of all hospital deaths. The patient demographics, clinical presentation, investigations, details of cardiac surgery, and postoperative course were noted. All hearts had been cut as per the flow of blood and described in detail. NCC was classified as isolated lesions or
nonisolated when associated with other cardiac anomalies. Cases in which hyper-trabeculation was obligatory, as in hypoplastic right or left ventricular syndromes, were excluded.
Results In a span of 10 years, 13 cases were diagnosed as NCC among 9427 autopsies performed, giving an incidence of 0.14%. There were 6 males and 7 females with an age range of 4 months to 55 years (mean 12 years and 7 months). The clinical details are given in Tables 1 and 2. Ten were children, 6 (60%) of whom (including the case described above) had a coexisting congenital
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Table 1. Patients with noncompaction cardiomyopathy who underwent surgery. Case no.
Age/sex
Preoperative diagnosis
Surgery
Cause of death
1
4 months/F
PDA ligation
Refractory cardiac failure þ NCC
2 3. 4 5 6 7
5 months/M 1 year/F 1 year/F 1 year/M 46 years/F 55 years/M
PDA þ left-to-right shunt, CHB, moderate PH, NCC Mid-muscular VSD, severe PH, LVH Perimembranous VSD, severe PH, LVH Moderate ASD, Swiss-cheese VSD Tricuspid atresia Type 1c Rheumatic calcified mitral stenosis IHD, ejection fraction 60%
ICR of VSD ICR of VSD ICR of VSD, ASD PA banding MVR CABG
Refractory cardiac failure þ NCC Refractory cardiac failure þ NCC Pneumonia þ NCC Refractory cardiac failure þ NCC Refractory cardiac failure þ NCC Pulmonary thromboembolism þ NCC
ASD: atrial septal defect; CABG: coronary artery bypass grafting; CHB: complete heart block; ICR: intracardiac repair; IHD: ischemic heart disease; LVH: left ventricular hypertrophy; MVR: mitral valve replacement; NCC: noncompaction cardiomyopathy; PA: pulmonary artery; PDA: patent ductus arteriosus; PH: pulmonary hypertension; VSD: ventricular septal defect.
Table 2. Patients with noncompaction cardiomyopathy who did not have surgery. Case no.
Age/sex
Primary diagnosis
Cause of death
8 9 10 11 12 13
5 months/M 6 months/M 1.5 years/F 2 years/F 11 years/F 45 years/M
Viral myocarditis, EF 30% Large PDA (4 mm) Myocarditis, EF 15% Lower RTI þ CHD Rheumatic MR þ AF IHD, EF 15%–20%
Refractory cardiac failure þ NCC Refractory cardiac failure þ NCC Refractory cardiac failure þ NCC VSD, PS, refractory failure þ NCC Anaphylactic shock after benzathine/penicillin þ NCC Refractory cardiac failure þ NCC
AF: atrial fibrillation; CHD: congenital heart disease; EF: ejection fraction; IHD: ischemic heart disease; MR: mitral regurgitation; NCC: noncompaction cardiomyopathy; PDA: patent ductus arteriosus; PS: pulmonary stenosis; RTI: respiratory tract infection; VSD: ventricular septal defect.
7 cases operated on, 5 had a similar postoperative course with inability to wean off the ventilator and/or support, eventually culminating in failure and death. In all postoperative cases, surgical causes of failure such as inadequate repair or patch dehiscence (for septal defects) had been ruled out by echocardiography. In the isolated and nonisolated groups, the deep inter-trabecular recesses communicated with the cavity of the left ventricle but not with the coronary arterial circulation.
Discussion Figure 3. Transverse slice through the ventricles shows noncompaction of right ventricle (RV) and left ventricle (LV). The arrow points to a small trabecular muscular ventricular septal defect.
cardiac anomaly (Figure 3); the others had a clinical diagnosis of myocarditis or rheumatic heart disease (Figure 4). A family history of sudden death in a sibling was present in case no. 10. The other 3 patients were adults, all over 45 years of age, and were affected by either rheumatic or ischemic heart disease. Only one patient (case no. 1) had a diagnosis of NCC. Of the
Developmentally, the myocardium is a loose meshwork of trabeculae. Rearrangement of myofibers and coalescence of inter-trabecular spaces or recesses results in compaction or solidification of the myocardium. This phenomenon, which is important for the function of the heart as an effective pump, occurs between 5 to 8 weeks of gestation; NCC is said to result from arrest of this process. This morphology simulates reptilian heart which is made up entirely of non-compacted myocardium with sinusoids directly channelling blood from ventricular lumen to the myocardium. The non-compacted hearts are hence called snake or spongy hearts,
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Figure 4. (A) The opened out left ventricular (LV) inflow tract showing dilatation of the mitral valve annulus (MV). The anterior papillary muscle (APM) and posterior papillary muscle (PPM) are attenuated and flush with the endocardial surface of the LV. Note the rounding of the free margins of valve leaflets and reduced number of tendinous cords. (B, C) Hyper-trabeculations of the mid portion and apical third of the LV as seen from the inflow aspect, and (D) well brought out on transverse sections.
an appearance noted as early as 1926 by Grant.7 However, it is advocated to use the term noncompaction, and terms such as persistent sinusoids or hyper-trabeculation should be avoided in the light of developmental and evolutionary considerations.8 NCC is a genetically heterogeneous disorder linked to mutations of sarcomeric and non-sarcomeric proteins, and it occurs in sporadic as well as familial forms.9 Despite such advances, it remains an unclassified cardiomyopathy,1 although the American Heart Association has classified it as primary genetic cardiomyopathy.10 NCC can present in isolation or in combination with other congenital heart diseases or inherited systemic disorders. However, follow-up of patients with associated congenital heart disease has not been performed to evaluate the surgical outcome. In our series, 7 of 13 patients had an associated cardiac anomaly, but none had a demonstrable extracardiac disease. Although absence of coexisting congenital heart diseases is taken as a criterion for noncompaction, it should not be so, due to the clinical implications.6 The time of arrest of the process of compaction determines the degree and extent of noncompaction.11 The left ventricle and its apex are the last parts of the heart to undergo compaction. Consequently, the left ventricle is the most common chamber affected.
Furthermore, the cardiomyopathy may involve one or more of the 9 segments of the left ventricle (apical, 4 mid-ventricular, and 4 basal segments with an anterior, septal, lateral, and inferior segment each).12 The apex is always involved in NCC, as noted in all of our cases. Although right ventricular noncompaction has been described and reported,13,14 because it is extremely difficult to differentiate between a heavily trabeculated right ventricle and non-compacted myocardium, its true existence is controversial.4 The true prevalence of NCC is currently unclear. It is possible that before the advent of modern-day diagnostic imaging, noncompaction existed but was never diagnosed antemortem, or more often misdiagnosed. A recent rise in reports of NCC indicates an evolving awareness of the disease. The diagnosis is best established by echocardiography and/or magnetic resonance imaging;2,6,15,16 its prevalence in echocardiographic series varies from 0.014% to 1.3%.4,5,17 Our study revealed an incidence of 0.14% among the autopsied cases, but this may not be representative of the true prevalence of the disease. Three of the patients were adults and the other 10 were children. In the pediatric population, NCC is the third most common type of primary cardiomyopathy, after dilated and hypertrophic cardiomyopathy.18 The functional implication
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Asian Cardiovascular & Thoracic Annals 23(2)
of the abnormal myocardium such as increased myocardial fibrosis can be assessed using newer techniques.19 Apart from moderate to marked endocardial fibrosis and subendocardial ischemia, myocardial fibrosis was not seen in any of these cases; regional fibrosis was present in adult patients with ischemic heart disease. The clinical features are extremely variable. The patient can remain asymptomatic for decades only to be decompensated by stress, or NCC can present with overt symptoms in the first few years of life, usually in the form of heart failure, conduction abnormalities, or embolic events, no different from the more frequent dilated cardiomyopathy.2 Although diagnostic echocardiographic and magnetic resonance imaging criteria have distinct cutoffs, the symptomatology may not be equivalent, resulting in a clinical-radiological mismatch. Hence we can have a patient with subtle heart failure but falling short of the diagnostic criteria, as well as an asymptomatic patient fulfilling the diagnostic criteria. Further, echocardiography is operatordependent. The experience of the echocardiographer can definitely affect missed noncompaction. Existing diagnostic criteria have also been questioned, and the right measurements have to be taken in the right view and in the right phase of the cardiac cycle.20 Although cardiac magnetic resonance imaging is useful to confirm the diagnosis of noncompaction complementary to echocardiography, it does not form part of the standard work-up for a cardiac patient. Such problems are magnified when the patients first undergo heart surgery. To our knowledge, no series has analyzed postoperative patients with coexisting NCC. In our series, only one patient was diagnosed conclusively with noncompaction on echocardiography. The varied clinical presentation gives yet another reason to miss the diagnosis. Symptoms and signs are more likely to be attributed to the primary cardiac disease (congenital or acquired) needing surgery, rather than to noncompaction. The 3 cases of isolated NCC were diagnosed as myocarditis or rheumatic mitral regurgitation. As the clinical presentation is varied, treatment is symptom-directed, predominantly involving management of heart failure. Arrhythmias need pacing devices. Thromboembolic episodes demand anticoagulation, or prophylactic anticoagulation is indicated in patients without such episodes but with rhythm disturbances. Heart transplantation has been described as a successful modality for the ultimate treatment of noncompaction. As modern day cardiac surgery strives for perfection, no stone should be left unturned to prevent morbidity and mortality. It is time to recognize noncompaction as an entity with surgical implications. We hypothesize that failure of the myocardium as an effective pump
resulted in the detrimental postoperative courses of our patients in the form of refractory failure, the noncompaction being unmasked due to perioperative stress. Hence even considering the diagnosis during an unexpected postoperative recovery can be helpful to cope with the problem and the likely prognosis. A clinical triad of heart failure, arrhythmias, and thromboembolic events should lead to a strong suspicion of noncompaction, especially with the coexistence of other congenital anomalies, muscle dystrophies, mitochondrial myopathies, or neuropathies, but no conclusive syndromes have been proven due to the small number of cases. As missing noncompaction is not impossible, screening for it should be part of the standard protocol. Because views and measurements are specific, even a possibility should prompt further evaluation. Clinical findings of myocarditis, unexplained low ejection fraction, recurrent congestive heart failure, or dilated cardiomyopathy are worth considering as noncompaction until proven otherwise, at least in the pediatric population. Family screening and genetic screening should be carried out in case there is history of cardiomyopathy. It is worth reiterating that even a diagnosis of dilated or hypertrophic cardiomyopathy in a relative may actually be noncompaction. For the surgeon, diagnosing a patient needing cardiac surgery as having noncompaction increases the possible postoperative complications exponentially, as we experienced in our case of patent ductus arteriosus ligation. It is also possible that the patient can have an absolutely uneventful recovery, reflecting the clinical spectrum of the disease. When surgery is inevitable, discussion with the family of the possible implications and weighing the potential risks and benefits of surgery is necessary. Ventricular assist devices and extracorporeal membrane oxygenation should be a part of the surgical armamentarium. As our study was an autopsy review, the incidence of noncompaction may not be indicative of the actual prevalence of the disease. Because not all deaths undergo autopsies and clinicians would be more likely to opt for an autopsy when the cause of death is unclear, there may be a selection bias. The clinical profile of the 13 patients was extremely heterogeneous, thus there could be several confounding factors coming into play which could have affected outcomes. Although all other obvious causes were ruled out, there can be no way to definitely say that the cause of death was noncompaction although we are sure that it significantly affected the outcome. Our study highlights the need for strict clinical vigilance to diagnose noncompaction. Existing diagnostic criteria need reappraisal to include cases of noncompaction associated with other congenital anomalies. Further, no definitive guidelines exist when a patient
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with noncompaction faces surgery, hence more studies are needed to reveal the surgical impact of this disease. Funding This research received no specific grant from any funding agency in the public, commerical, or not-for-profit sectors.
Conflict of interest statement None declared.
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![[Noncompaction cardiomyopathy].](/assets/img/hold.png)
