There is no specific treatment for LVNC. Nevertheless, the early and precise diagnosis is mandatory to rule out other underlying diagnoses and to allow a timely start of standard heart failure and anticoagulation therapy which may prevent further complications.
Our study provides redefined and extended CMR criteria for diagnosing and discriminating LVNC from other cardiomyopathies. These four basic criteria are (Table 4)
Percentage LV-MMnon-compacted >25 %
Total LV-MMInon-compacted >15 g/m2
Non-compacted/compacted myocardium ratio of ≥3:1 in at least one of the other segments (1–3, 7–16) excluding the apical segment 17
Trabeculation in segments 4–6 ≥ 2:1 (non-compacted/compacted)
There are some studies using echocardiographic criteria for diagnosing LVNC [2, 5]. However, this approach is highly investigator-dependent, diagnosis is based on two-dimensional planes using semi-quantitative or qualitative criteria and specificity is low . Two-dimensional CMR criteria derived from echocardiography [11, 24] offer a better visualization of all regions of the LV but suffer from the same fundamental limitations. One major advantage of CMR is the three-dimensional approach, which allows for imaging of the entire volume of the heart with lower investigator dependency and without limitations caused by a patient’s constitution. Our results demonstrated a good reproducibility with low intra- and interobserver variability. Jacquier et al.  were first to measure the total amount of trabeculation and to propose a cut-off value above which the diagnosis of LVNC is likely. However, in their study endocardial contours were traced along the tip of LV trabeculation towards the LV cavity and therefore intertrabecular blood pool was included in the trabeculated mass, especially in LVNC patients.
In the present study we tried to overcome these limitations by excluding blood pool from the assessment of LV-MMInon-compacted. Additionally the purpose of this study was to analyse the occurrence of LGE in LVNC.
We performed genetic analysis in two patients in which, however, mutation screening was negative. A recent work showed that the LVNC patients with mutations in sarcomere genes are phenotypically not distinct from those without a mutation . A negative genetic analysis of six sarcomere genes, like in our study, does therefore not rule out the diagnosis of LVNC. There is a wide variety in the location of the gene mutation, which can make the effort required for genetic analysis unreasonably high. The pedigree analyses are more often helpful and indicated an autosomal dominant mode of inheritance in these two patients.
Mass and distribution of LV trabeculation
Compared with Jaquier et al. results , our study shows some discrepancies in regard to LV volumes and masses. LV-MMInon-compacted was lower in all patient groups and controls in the present study, which is most likely the result of the exclusion of blood pool. However, percentage LV-MMnon-compacted of LVNC patients was similar, meaning that LV-MMIcompacted was lower in our group. This might be explained by the female predominance in our LVNC cohort (Table 2). In the same group we also found a lower LV-EDVI; however, our group was younger and presented with an LV-EF within a lower normal range (Table 3) compared with the clearly impaired LV function of the LVNC cohort of the cited study. The aforementioned differences result in a minor discrepancy of the percentage LV-MMnon-compacted (25 % vs. 20 %). Nevertheless, both studies clearly demonstrate that it is possible to diagnose LVNC using this parameter. The distinct assessment of LV trabeculation in the present study additionally allows for introduction of a total LV-MMInon-compacted cut-off value of 15 g/m2 (Fig. 4), making it is possible to diagnose LVNC independently of the mass of the compacted myocardium.
According to literature data, the distribution of TS in LVNC is controversial. In a large echocardiographic study with 34 patients the authors found TS in the midventricular and apical segments . Jacquier et al. did not find a specific distribution of TS in LVNC patients compared to DCM, HCM and controls . In the present study we could demonstrate that trabeculation in the segments 4–6 (Fig. 5) alludes to a high probability for LVNC (Fig. 3a). Only one HCM patient also showed trabeculation in these segments with a ratio of non-compacted/compacted myocardium of <2:1. As demonstrated in Fig. 3a the degree of trabeculation can also be considered as a good discriminator between LVNC and the other patient cohorts and controls. In the LVNC cohort the number of segments with a non-compacted/compacted myocardium ratio of ≥3:1 is highest by far not only in the basal and midventricular but also in the apical segments. The use of a myocardial compacted/non-compacted ratio is a common criterion for diagnosis of LVNC in both echocardiographic and CMR studies. However, there is controversy regarding the ratio value and whether it should be measured in end-systole or end-diastole. Petersen et al. considered a CMR ratio between the non-compacted and the compacted layer of >2.3:1 diagnostic for LVNC . Applying this ratio to our study cohort (Fig. 3b) we achieved sensitivities of 100 % and specificities of 80 % (excluding segment 17) or 58 % (including segment 17). The specificities were much lower than in the cited study and also lower as compared to our single or combined criteria we propose (Table 4). Furthermore, the PPV was only 57 % and 39 % respectively. In the present study we found many HCM and DCM patients with a non-compacted/compacted ratio between 2:1 and 3:1. Of these some had a ratio of >2.3:1. These patients impair the specificity of the cited cut-off value as too many HCM and DCM patients have false positive results for LVNC.
The discrepancy between the study results could be caused by a different approach in the measurement of the thickness of compacted and non-compacted myocardium. Petersen et al.  used three long-axis views, whereas in our study short-axis views were used (except for segment 17).
A second possible explanation might be differences in the HCM and DCM patient cohorts; however, no details about these patients are provided in Petersen et al.’s report .
LVNC and LGE
None of our LVNC patients presented with myocardial LGE (Fig. 6). Our findings are in line with other studies that also stated a lack of LGE in LVNC [27, 28]. On the other hand, there are also studies that do report LGE findings [13, 29–31].
The reasons for these discrepancies remain unclear. Firstly, the presence or absence of LGE does probably not depend on patient age as the mean age of our LVNC cohort without LGE (35 years) is framed by the mean ages of two patient groups with positive LGE [13, 31]. Secondly, there was no significant difference in the mean LV ejection fraction between our LVNC patients and the patients of one study . Finally all cited imaging studies were performed using 1.5-T MR systems. However, the authors of the largest cited study  used a T1-weighted inversion recovery gradient echo sequence, depending on correct adjustments of inversion time , whereas a smaller study without positive LGE findings in LVNC patients used a more modern phase-sensitive inversion recovery sequence, which has shown advantages in visualisation of fibrosis in regard to image quality and reproducibility compared with standard magnitude detection . Therefore, the contradictory LGE findings in the present and the cited studies might be partly caused by differences in imaging techniques.
The described macroscopic LGE patterns in LVNC patients varied substantially from subendocardial, transmural, intramyocardial to subendocardial [13, 30] and no specific or at least typical enhancement patterns for LVNC patients have been described so far. Therefore, especially in the adult group, an additional underlying coronary artery disease or e.g. postinflammatory changes causing different patterns of LGE described in LVNC patients have to be excluded to be sure that the macroscopic LGE is indeed an intrinsic finding of LVNC and not an epiphenomenon caused by other coexisting diseases.
The absence of LGE in our study cohort better corresponds with the theory of a developmental arrest [4, 5] as the underlying pathophysiology of LVNC than with the competing theory of a traumatic or ischemic pathophysiology . According to the latter theory one would expect scar tissue and typical patterns of LGE in each LVNC patient. In developmental arrest though, caused by a genetic mutation, the absence of such alterations would not be contradictory. However, this might be a premature conclusion as the LGE technique might just overlook some cases of fibrosis as a result of the given spatial resolution.
The presence, pathophysiology and meaning of LGE in LVNC patients need to be confirmed by further studies with a genetic diagnosis and a larger sample size to increase statistical power and to potentially identify risk factors for developing fibrosis in LVNC.
Genetic analysis was performed only in two LVNC patients with familial disease. However, no gene mutation could be identified indicating that other genes may be involved in the genetic aetiology of LVNC. A cohort of LVNC patients with a genetic diagnosis would increase the reliability of a CMR-derived diagnosis.
Owing to the prevalence of LVNC the study population was small in terms of statistical means. Multicentre studies are necessary to confirm our findings in a larger patient cohort.
Furthermore, CMR follow-up examinations would be helpful to assess a potential change of non-compacted or compacted mass in a chronological sequence.
In conclusion, CMR can distinguish LVNC from other cardiomyopathies and normal hearts with high sensitivity and specificity. In our study we introduce highly reproducible volumetric cut-off values and two semi-quantitative criteria. The role of the absence or presence of LGE in LVNC has to be further investigated.