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A few more pieces in the puzzle of non‐compaction cardiomyopathy

2011; Elsevier BV; Volume: 13; Issue: 2 Linguagem: Inglês

10.1093/eurjhf/hfq233

1879-0844

H. Marco Willemsen, Maarten P. van den Berg,

Cardiac Structural Anomalies and Repair

This editorial refers to ‘Myocardial fibrosis in isolated left ventricular non-compaction and its relation to disease severity’ by Gaetano Nucifora et al. and ‘Isolated left ventricular non-compaction in adults: clinical and echocardiographic features in 105 patients. Results from a French registry’ by Gilbert Habib et al. published in this issue on pages 170–176 and 177–185. Non-compaction cardiomyopathy (NCC) is increasingly recognized as an important cause of heart failure. Although it is still ‘classified’ by the European Society of Cardiology as an unclassified cardiomyopathy,1 it is considered a distinct cardiomyopathy by the American Heart Association.2 Non-compaction cardiomyopathy presents typically with a triad of: heart failure symptoms, arrhythmias, and embolic events. The main reason why NCC is diagnosed much more often nowadays is obviously the great improvement in imaging modalities, including echocardiography and cardiac magnetic resonance imaging (MRI), which in turn increases awareness among clinicians about NCC. What do we know of NCC? The key histological finding is spongy myocardium, characterized by prominent and excessive trabeculations with correspondingly deep recesses within the hypertrophied wall.3 It is widely thought that the basic mechanism involved in NCC is an abnormal arrest in embryonic endomyocardial morphogenesis, but definitive proof of this assumption is still lacking to date and other mechanisms may well play a role.4 Furthermore, it is assumed that without the process of compaction of the endocardium, capillary networks are not formed, leaving non-compacted endocardial islands which are poorly connected to the coronary circulation. This in turn is a substrate for ischaemia and infarctions. Secondary pathogenetic processes thought to be involved in non-compaction include: dissection of the myocardium, frustrated attempts at myocardial hypertrophy, myocardial tearing caused by dilatation, and compensatory hypervascularization.4 The diagnosis of NCC is difficult and can often be delayed for many years.3 In some cases, the diagnosis is incorrect, particularly in the case of prominent physiological trabecularizations. The criss-crossing meshwork of thin muscle bundles at the apical third of the left ventricle and thick muscle bundles aligning the myocardial wall are normal structures.5 Furthermore, false tendons extending between the septum and the papillary muscles are very common in normal hearts (prevalence >50%)6 and there can also be multiple bellies of the papillary muscle or there may be additional papillary muscles.7 All of these normal trabecularization patterns can significantly influence cardiac MRI readings, as shown by Weinsaft et al.8 Furthermore, other cardiomyopathies and disease states can be mistaken for NCC. For example, pathology data from 22 patients with dilated congestive cardiomyopathy and 13 patients with ischaemic heart disease showed hypertrabecularization resembling NCC in 43 and 28% of cases, respectively.9 To account for the above diagnostic problems, rigid echocardiographic criteria have been devised by Jenni et al.10 and Stollberger et al.4 These diagnostic criteria for NCC are as follows: (i) appearance of at least four prominent trabeculations and deep intertrabecular recesses; (ii) appearance of blood flow from the ventricular cavity into the intertrabecular recesses as visualized by colour Doppler imaging; (iii) the segments of non-compacted myocardium mainly involve the apex and the inferior and lateral left ventricular wall, and typically show a two-layered structure with a ratio >2 between the non-compacted subendocardial layer and the compacted subepicardial layer at end-systole; and (iv) the absence of coexisting cardiac abnormalities. Besides echocardiography, cardiac MRI is a promising imaging modality for diagnosing NCC. Modern CINE sequences have ideal contrast between the left ventricular cavity and hypertrabecularizations; in addition MRI is not limited by poor imaging quality due to thoracic air or fat. A specific MRI criterion is currently used for diagnosing NCC: the ratio of non-compacted to compacted myocardium should be >2.3. This ratio is based on a study by Petersen et al. who showed that the ratio discriminated well between NCC vs. hypertensive left ventricular cardiomyopathy, left ventricular hypertrophy due to aortic stenosis patients, and hypertrophic cardiomyopathy.11 However, this ratio has not been tested in the general population. Obviously, in the general population, the a priori chance of finding NCC in individual cases is low, and the specificity of the ratio in this setting might not be high enough, resulting in many false positive findings. In addition, since cardiac MRI slices are 5–8 mm thick, when a trabecularization crosses through this slice in a parallel manner, the trabecularization appears much thicker because the MRI slice images it ‘flatly’ from the entry to the exit site from the slice. This kind of ‘foreshortening’ can also happen in echocardiography but to a much lesser extent due to better resolution. As a consequence, there is a risk with MRI of exaggerating the mass measurement of trabecularization, thereby easily exceeding the recently established cut-off value of 20% (trabecularization as a percentage of global left ventricular mass), above which NCC is very likely.12 On the other hand, MRI can offer additional valuable information about patients with suspected NCC, because it provides very reliable data on left ventricular volumes and ejection fraction, and it also affords characterization of myocardial tissue. In particular, direct imaging of myocardial fibrosis is possible with the use of an inversion recovery prepared T1-weighted gradient-echo sequence using gadolinium (delayed contrast enhancement).13 In the present issue of the European Journal of Heart Failure, Nucifora et al.14 report a study in a group of patients diagnosed with NCC using MRI. Although this is not the first study, the interesting feature of the study is the elaborate analysis of fibrosis using delayed contrast enhancement imaging. The main finding was a strong relation between the presence and extent of delayed enhancement on the one hand and clinical status and left ventricular ejection fraction on the other. In addition, the investigators analysed the location of the delayed enhancement. With non-compacted myocardium and associated infarction being located endocardially, one would expect the delayed enhancement to also be located endocardially, and predominantly in the non-compacted myocardium. However, most delayed enhancement was observed mid-myocardially or at the site of insertion of the right ventricle into the left ventricle, in fact much like in dilated cardiomyopathy and hypertrophic cardiomyopathy, respectively.15 Also, there was equally delayed enhancement in compacted as in non-compacted myocardium. As an explanation for these unexpected but interesting findings, the authors argued that increased wall stress caused by progressive left ventricular remodelling may result in myocyte necrosis preferentially affecting the mid-myocardial layers, which would also explain the relation between the presence and extent of delayed enhancement with left ventricular ejection fraction and clinical status. The authors also speculated that ‘diminished coronary flow reserve’ in compacted as well as non-compacted myocardium16 could play a role in the equally delayed enhancement in compacted and in non-compacted myocardium. However, it remains to be proven whether these explanations are correct. Another possible explanation not referred to by the investigators relates to the actual diagnosis. Although the investigators used strict MRI criteria to diagnose NCC, and in most cases the diagnosis was probably correct, using MRI as the sole diagnostic technique for NCC is questionable. Perhaps some patients in fact suffered from other forms of cardiomyopathy (e.g. dilated cardiomyopathy or hypertrophic cardiomyopathy) accompanied by hypertrabecularizations. Further studies are clearly needed to confirm whether the intriguing delayed enhancement patterns described by Nucifora et al. are a true feature of NCC and whether their explanations are correct. With the study of Habib et al.17 also published in the present issue of the journal, a large follow-up study is now available. The study included 105 patients with a very probable diagnosis of NCC, and many complications occurred during an average follow-up of 2.33 years: severe heart failure in 33 patients, heart transplantation in 9, ventricular arrhythmias in 7, embolic events in 9, and 12 patients died. This is a rather high complication and mortality rate. In addition, NCC was identified by familial screening in eight asymptomatic patients (8%), attesting to the familial nature of NCC in a sizeable number of cases. The authors must be commended for using strict imaging criteria and appropriately excluding other forms of cardiomyopathy. In fact, Habib et al. excluded 49 out of the 154 patients identified with presumed non-compaction cardiomyopathy, because of doubt about the diagnosis. A limitation not mentioned by the authors is the short follow-up, but this actually supports the poor prognosis of patients with NCC. On the other hand, it should be realized that there are probably many subjects in the general population with silent NCC who have a good prognosis. Nevertheless, based on the results of this straightforward study, it is now beyond doubt that NCC, once diagnosed in symptomatic patients, is a serious disorder, necessitating strict follow-up and medical care as well as family screening. In conclusion, the studies by Nucifora et al. and Habib et al. have provided a few more pieces in the puzzle of NCC, but more studies are needed to further characterize this intriguing entity. One issue is the fact that medical treatment of patients with NCC is not yet well established and studies to investigate the most appropriate treatments for patients with NCC are eagerly awaited. Conflict of interest: none declared.