Author + information
- Received September 21, 2018
- Revision received December 18, 2018
- Accepted December 20, 2018
- Published online March 13, 2019.
- Chrysanthos Grigoratos, MDa,b,
- Andrea Barison, MD, PhDa,
- Alexander Ivanov, MDc,
- Daniele Andreini, MD, PhDd,e,
- Mihaela-Silvia Amzulescu, MDf,
- Lukasz Mazurkiewicz, MD, PhDg,h,
- Antonio De Luca, MDa,
- Jacek Grzybowski, MD, PhDg,
- Pier Giorgio Masci, MD, PhDi,
- Magdalena Marczak, MD, PhDh,
- John F. Heitner, MDc,
- Juerg Schwitter, MD, PhDi,
- Bernhard L. Gerber, MD, PhDf,
- Michele Emdin, MD, PhDa,b and
- Giovanni Donato Aquaro, MDa,∗ ()
- aFondazione Gabriele Monasterio CNR/Regione Toscana, Pisa, Italy
- bInstitute of Life Sciences, Scuola Superiore Sant’Anna, Pisa, Italy
- cDepartment of Cardiology, New York Methodist Hospital, Brooklyn, New York
- dCentro Cardiologico Monzino, IRCCS, Milan, Italy
- eDepartment of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy
- fDivision of Cardiology, Department of Cardiovascular Diseases Cliniques St. Luc and Pôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
- gDepartment of Cardiomyopathies, Institute of Cardiology, Warsaw, Poland
- hCMR Unit, Institute of Cardiology, Warsaw, Poland
- iDivision of Cardiology and CMR-Center, University Hospital Lausanne, Lausanne, Switzerland
- ↵∗Address for correspondence:
Dr. Giovanni Donato Aquaro, Fondazione Gabriele Monasterio CNR/Regione Toscana, via Moruzzi 1, Pisa 56100, Italy.
Objectives The objective of this meta-analysis was to assess the predictive value of late gadolinium enhancement (LGE) and global systolic impairment for future major adverse cardiovascular events in left ventricular noncompaction (LVNC).
Background The prognosis of patients with LVNC, with and without left ventricular dysfunction and LGE, is still unclear.
Methods A systematic review of published research and a meta-analysis reporting a combined endpoint of hard (cardiac death, sudden cardiac death, appropriate defibrillator firing, resuscitated cardiac arrest, cardiac transplantation, assist device implantation) and minor (heart failure hospitalization and thromboembolic events) events was performed.
Results Four studies with 574 patients with LVNC and 677 with no LVNC and an average follow-up duration of 5.2 years were analyzed. In patients with LVNC, LGE was associated with the combined endpoint (pooled odds ratio: 4.9; 95% confidence interval: 1.63 to 14.6; p = 0.005) and cardiac death (pooled odds ratio: 9.8; 95% confidence interval: 2.44 to 39.5; p < 0.001). Preserved left ventricular systolic function was found in 183 patients with LVNC: 25 with positive LGE and 158 with negative LGE. In LVNC with preserved ejection fraction, positive LGE was associated with hard cardiac events (odds ratio: 6.1; 95% confidence interval: 2.1 to 17.5; p < 0.001). No hard cardiac events were recorded in patients with LVNC, preserved ejection fraction, and negative LGE.
Conclusions Patients with LVNC but without LGE have a better prognosis than those with LGE. When LGE is negative and global systolic function is preserved, no hard cardiac events are to be expected. Currently available criteria allow diagnosis of LVNC, but to further define the presence and prognostic significance of the disease, LGE and/or global systolic impairment must be considered for better risk stratification.
- late gadolinium enhancement
- left ventricular noncompaction
- systolic impairment
The first description of left ventricular noncompaction (LVNC) goes back almost 40 years (1); nevertheless, scientific interest remains high. Whether isolated LVNC represents simply a peculiar presentation of various forms of nonischemic cardiomyopathy (NICM) or a distinct cardiomyopathy is still under debate (2). Moreover, the prevalence of isolated LVNC in various studies differs significantly (3–5) and clinical presentation is rather heterogeneous, ranging from subclinical forms to overt symptoms and even cardiac death (6,7). Hypertrabeculation may also be observed in otherwise healthy subjects, and no association has been described in an asymptomatic population of representative subjects between the extent of left ventricular (LV) trabeculation and cardiac structure and function over long-term follow-up (8).
In vivo diagnosis made noninvasively mainly by echocardiography or cardiac magnetic resonance (CMR) (9) is based on particular phenotypic characteristics and distinctive morphological appearance. The typical manifestation includes a thin compacted myocardium and a conspicuous, noncompacted, hypertrabeculated layer with deep intertrabecular recesses. Some investigators postulate that this particular pathognomonic appearance, at least in some forms of LVNC, could be secondary to interruption of the myocardial compaction process during embryogenesis (10). Among different noninvasive diagnostic criteria proposed in recent years, with different specificity and sensitivity, currently the most frequently used for CMR are those described by Petersen et al. (11), Stacey et al. (12), Jacquier et al. (13), Grothoff et al. (14), and Captur et al. (15). All available criteria, however, provide LVNC diagnosis regardless of global or regional systolic impairment and/or the presence of additional pathological features such as myocardial fibrosis. Moreover, no LVNC diagnostic criteria have shown a strong correlation with clinical outcomes. On this matter, the scientific community’s interest has recently shifted from LVNC epidemiology and diagnostic accuracy toward a more clinical and prognostic approach. Previous small-population studies evaluated the prognostic role of LVNC (16,17). However, in all these studies, the majority of patients with LVNC had positive late gadolinium enhancement (LGE) and/or LV dysfunction (18–21). Therefore, the true prognostic significance of LVNC with preserved LV function and negative LGE has been scarcely investigated. Thus, the aim of this meta-analysis was to investigate the association of LV systolic impairment and myocardial fibrosis assessed by means of LGE in patients with CMR diagnoses of LVNC for the prediction of hard cardiac events. The presence of myocardial fibrosis and global systolic function could potentially act as discriminative factors of prognosis regardless of the presence, extent, or localization of myocardial hypertrabeculation in LVNC.
This meta-analysis was conducted in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The review protocol considered all studies fulfilling the following eligibility criteria: prospective or retrospective analysis of patients with LVNC diagnoses undergoing CMR with administration of gadolinium-based contrast agent and LGE assessment and studies exclusively published in peer-reviewed journals, in English, with at least 45 patients enrolled and detailed prognostic information with follow-up of at least 12 months. All studies not fulfilling all of the aforementioned criteria were excluded from subsequent analysis. The search included all variations of terms used in the published research for “left ventricular non-compaction” and “hyper trabeculation,” and all these terms were combined with one of the following keywords: “prognosis,” “ejection fraction,” “LGE,” “late gadolinium enhancement,” “injury,” “fibrosis,” “scar,” and “heart failure” (HF).
Two authors (C.G. and G.D.A.) performed the search and selection of titles on the basis of the pre-specified keywords. Titles and abstracts of all studies were assessed. Duplicates and studies not satisfying meta-analysis purposes were excluded, whereas all other papers were deemed relevant and full papers were retrieved. We searched PubMed/MEDLINE, the Cochrane Database of Systematic Reviews, the Cochrane Methodology Register, and the Cochrane Central Register of Controlled Trials. By research query, 1,289 papers were found (Figure 1). Of these, 1,267 studies were excluded either because they were duplicates or for other reasons, such as irrelevant data with respect to the study aims, reviews, no prognostic information, or no CMR performed. Full text was then retrieved for the remaining 22 studies, and subsequently an additional 18 were excluded. Four studies were excluded because only pediatric patients were evaluated, 1 was a review, 1 considered only echocardiographic parameters, 2 provided no prognostic information, 3 did not assess myocardial fibrosis assessed by LGE, 2 considered only right ventricular systolic impairment as a prognostic indicator, and 3 included patients with specific comorbidities only (muscular dystrophy in 2 studies and beta-thalassemia in 1 study). The remaining 4 studies were considered for subsequent analysis. Two studies considered patients with LV global systolic impairment only, whereas the other 2 studies included both patients with normal and impaired LV global systolic function. A Quality of Reporting of Meta-Analyses diagram with selection progression is given in Figure 1.
Finally, the risk for bias of these 4 studies was assessed using the Newcastle-Ottawa Scale for evaluating the quality of nonrandomized studies in meta-analysis (22). Briefly, the quality of the included studies evaluated 3 factors: 1) selection of patients, including the definition of patients with LVNC and control subjects, the adequacy of the selection of patients with LVNC and control subjects, representativeness of the patients with and without LVNC, and demonstration that the endpoint was absent at enrollment; 2) comparability, assessing the study design and analysis and the adjustment for confounding factors; and 3) outcome, including the modality of assessment of endpoints, the adequacy of follow-up length, and the completeness of follow-up by assessing whether follow-up was completed for at least 95% of patients or in <95% (or in case of absent description). A “star” was assigned for each of these points, and “good” quality was assessed in presence of >2 stars for selection of patients, ≥1 star for comparability, and ≥2 stars for outcome. All the selected studies had “good” quality scores.
All available data from the studies included in the analysis were collected, and additionally, the first investigator of each study was contacted and agreed to participate in the meta-analysis by sharing missing data for better prognostic characterization as well as additional information regarding the total number of patients with and without LGE and with and without LV systolic impairment. Original studies databases or other CMR parameters were not collected. The prognostic composite endpoint comprised the following events: cardiac death, sudden cardiac death (SCD), appropriate implantable cardioverter-defibrillator (ICD) firing, resuscitated cardiac arrest, cardiac transplantation, left ventricular assist device (LVAD) implantation, HF hospitalization, ischemic stroke, and other thromboembolic events. Hard cardiac events including cardiac death, SCD, appropriate ICD firing, cardiac arrest, cardiac transplantation, and LVAD implantation were also separately evaluated. To ensure that LVNC diagnosis among the 4 studies was as homogeneous as possible, the frequently used criterion for LVNC diagnosis as proposed by Petersen et al. (11) was considered. When not available, LVNC diagnosis was made with whatever criterion was considered by the investigators.
Statistical analyses were performed using MedCalc for Windows version 15.0 (MedCalc Software, Ostend, Belgium). Heterogeneity among studies was assessed by means of the Cochrane Q statistic and I2 statistic. We also performed a fixed-effects meta-regression of the natural logarithm of the odds ratio (OR) for the combined endpoint, cardiac death, and hard cardiac events for the factors of age, left ventricular ejection fraction (LVEF), and LV end-diastolic volume. Meta-regression was performed using SSPS version 20 (IBM, Armonk, New York). A funnel plot of the logarithm of effect size and comparison with the standard error for each trial was used to evaluate publication bias. The OR of each study was then recalculated using raw event data with a 2 × 2 table. A summary OR was calculated using a random-effects model from the OR and the 95% confidence interval (CI) for each endpoint in each study using Mantel-Haenszel methods. To assess the sensitivity of the meta-analysis of each outcome, sensitivity analysis, which consisted of exclusion of 1 study at a time, was performed. A p value <0.05 was considered to indicate statistical significance.
All 4 studies included were conducted with a sufficient number of patients, long enough follow-up, and CMR diagnosis of LVNC made according to at least 1 of the aforementioned criteria (11–15). Table 1 shows the total number of patients enrolled in each study, the LVNC criterion used for diagnosis, as well as inclusion and exclusion criteria considered. Clinical characteristics and CMR parameters are summarized in Tables 2 and 3⇓⇓, respectively. Table 4 depicts clinical outcomes and the follow-up duration of each study included in the meta-analysis.
In the multicenter study by Andreini et al. (19), 113 patients with diagnosis of LVNC by echocardiographic and CMR criteria were enrolled. In this study, a control group of subjects without LVNC was not included. The average LVEF was 45 ± 15%, and 82 patients had LV dysfunction (LVEF <50%). During the average follow-up period of 47 ± 20 months, 36 events occurred in patients with LVNC (16 HF hospitalizations, 10 ventricular arrhythmias, 5 thromboembolic events, and 5 cardiac deaths). Ten events occurred among the 11 patients with positive LGE, 32 among the 82 patients with LV impairment (LVEF <50%), and 4 (2 HF hospitalizations and 2 ischemic strokes) among the 30 patients with preserved LV function and negative LGE.
In the study by Ivanov et al. (21), 276 patients had positive CMR criteria for LVNC, while 424 patients did not. Patients with LVNC and control subjects had similar clinical presentation and LV function (LVEF 49 ± 17% in patients with LVNC vs. 51 ± 16% in control subjects; p = 0.11). Eighty-four patients with LVNC had positive LGE, and 115 had LV systolic impairment. During an average follow-up period of 7 years, 30 events occurred in the group of patients with LVNC with positive LGE (7 cardiac deaths, 1 ischemic stroke, 2 ventricular fibrillation or ventricular tachycardia, and 20 HF hospitalizations), 45 events among the patients with LVNC and LV systolic impairment (10 cardiac deaths, 4 ischemic strokes, 5 ventricular fibrillation or ventricular tachycardia, and 26 HF hospitalizations), and 9 events occurred among the 128 patients with LVNC, normal LVEFs, and negative LGE (1 ischemic stroke and 8 HF hospitalizations).
Amzulescu et al. (18) enrolled 58 patients with CMR criteria of LVNC and 104 patients without. All patients enrolled had LV impairment (LVEF 25 ± 8% in patients with LVNC vs. 25 ± 9% in those without LVNC; p = 0.99). Patients were followed for an average of 3.4 years. During follow-up in the LVNC group, 11 patients had the combined endpoint of cardiovascular death, LVAD implantation, resuscitated cardiac arrest, cardiac transplantation, or appropriate device shocks. Twenty-two patients had LGE with 5 events (3 cardiac deaths, 1 appropriate ICD shock, and 1 cardiac transplantation). Among the patients without LVNC, 18 events occurred, including 8 cardiac deaths.
Mazurkiewicz et al. (20) included 127 patients with CMR criteria of LVNC and 149 without. All patients had LV impairment, with a significant difference between patients with and without LVNC (LVEF 27 ± 7% in patients with LVNC vs. 24 ± 10% in those without LVNC; p = 0.002). LGE was positive in 46 patients with LVNC. Thirteen patients with LVNC had cardiac events (6 cardiac deaths, 4 transplantations, 2 strokes, and 1 LVAD implantation) during the average follow-up period of 4 years.
Overall, the 4 studies included 574 patients with LVNC and 677 without LVNC. The combined endpoint was reached in 121 patients with LVNC (21%) and in 135 patients without LVNC (20%) (p = 0.96). Cardiac death occurred in 27 patients with LVNC (5%) and in 35 without LVNC (6%) (p = 0.79). No significant difference between patients with and those without LVNC for the combined endpoint (pooled OR: 0.94; 95% CI: 0.69 to 1.3; p = 0.67), cardiac death (pooled OR: 0.92; 95% CI: 0.53 to 1.6; p = 0.78) and for other events such as HF hospitalization and ischemic stroke (pooled OR: 1.44; 95% CI: 0.96 to 2.2; p = 0.08) was found, as shown in Figure 2. Cochrane Q and I2 statistics did not show significant heterogeneity for any endpoint for the comparison between patients with and those without LVNC.
In patients with LVNC, the combined endpoint occurred in 56 of 163 patients with positive LGE (34%) and in 65 of the 411 patients with negative LGE (16%). The meta-analysis of available data showed that LGE was significantly associated with the combined endpoint (pooled OR: 4.9; 95% CI: 1.63 to 14.6; p = 0.005), cardiac death (pooled OR: 9.8; 95% CI: 2.44 to 39.5; p = 0.001), and hard cardiac events (pooled OR: 4.1; 95% CI: 1.15 to 14.5; p = 0.03), although some heterogeneity of results was found among the studies (Figure 3).
Preserved LV systolic function (LVEF >50%) was found in 183 patients: 25 with positive LGE and 158 with negative LGE. In the group with preserved LV function, positive LGE was associated with combined endpoint (OR: 6.1; 95% CI: 2.1 to 17.5; p < 0.001). Eight events (32%) occurred in the group of patients with positive LGE and preserved LVEF (2 cardiac deaths, 1 resuscitated cardiac death, 1 ischemic stroke, and 4 hospitalizations for HF) and 13 (8%) in those with negative LGE and preserved EF (10 HF hospitalizations and 3 ischemic strokes) (p = 0.002). No hard cardiac events were recorded among the 158 patients with LVNC, preserved LVEF, and negative LGE (Figure 4). All aforementioned data are summarized in Table 5.
LGE presence was also associated with higher prevalence of both the combined endpoint (p < 0.001) and hard cardiac events (p < 0.001) among patients with LVNC and LV dysfunction.
Figure 5 shows that the pooled annualized event rate of cardiac death was significantly higher in patients with LVNC with LGE than those without (p = 0.034), whereas no significant differences were found for the combined endpoint and for hard cardiac events.
Funnel plots evaluating effect size versus study precision demonstrated no asymmetry, demonstrating the absence of publication bias for all endpoints.
Meta-regression analysis of the study-level covariates including age, LVEF, and LV end-diastolic volume was performed. We did not find any significant interaction between covariates and the combined endpoint. On contrast, a significant interaction was detected between age and cardiac death (p = 0.03) and between hard cardiac events and LVEF (p = 0.03) and LV end-diastolic volume (p = 0.03), which likely explains a portion of the heterogeneity seen for these outcomes.
We performed sensitivity analysis for the combined endpoint, cardiac death and hard cardiac events, for the meta-analysis comparing patients with LVNC with and without LGE.
The p value of the meta-analysis remained significant for the combined endpoint and cardiac death, regardless of the study removed from the analysis. For hard cardiac events, the p value for the outcome was not significant when we excluded the study by Ivanov et al. (21) (p = 0.10) or the study by Mazurkiewicz et al. (20) (p = 0.07).
This meta-analysis demonstrates that when matched for LVEF, patients with and those without LVNC have similar prognoses. LGE is associated with worse prognosis in patients with LVNC independent of LVEF. No hard cardiac events, defined as cardiac death, SCD, appropriate ICD firing, resuscitated cardiac arrest, cardiac transplantation, and LVAD implantation, occurred in patients with LVNC, preserved LVEF, and negative LGE.
More than 3 decades ago, postmortem studies described the presence and extent of myocardial fibrosis in dilated cardiomyopathy (23). Over the following years, with the advent of LGE CMR, easy and noninvasive myocardial fibrosis detection in patients with NICM became feasible. LGE detection and its clinical importance have been extensively studied, and abundant scientific evidence exists regarding the role of LGE as a predictor of future cardiac events in patients with NICM (24–28). Patients with LVNC included in this meta-analysis share the same prognostic characteristics as patients with NICM in the aforementioned studies (24–28). The presence of LGE was a predictor of major adverse cardiovascular events, and these patients had a worse prognosis than patients with LVNC without LGE. Therefore, this finding supports the hypothesis that LVNC in adult patients must be interpreted as a particular phenotypic appearance of NICM sharing the same clinical and prognostic characteristics as other patients with NICM but without the phenotypic appearance of LVNC.
LGE presence was significantly associated with worse prognosis in all selected studies except that of Amzulescu et al. (18). This may be explained by the unconventional method of analysis of LGE used by Amzulescu et al. (18) compared with the other studies (Andreini et al.  and Mazurkiewicz et al.  used the conventional >6 SD method, and Ivanov et al. used visual assessment). Moreover, evidence from this meta-analysis emphasizes the additive role of global systolic impairment in this cohort of patients. Global LV systolic impairment is a known predictor of adverse cardiac events regardless of symptoms, hence in both preclinical global systolic impairment (29) as well as in advanced HF (30). Once again, data from this meta-analysis showed that LVNC was not associated with worse prognosis compared with patients matched for LVEF. In the clinical scenario of LVNC, the presence or not of global systolic impairment could help identify patients with adverse prognosis and therefore act accordingly.
Last, and given the aforementioned findings, data from subjects with LVNC regarding both LGE and global systolic impairment were combined. By doing so, we observed that in patients with LVNC with preserved global systolic function (LVEF >50%) and negative LGE, no hard cardiac events, defined as cardiac death, SCD, appropriate ICD firing, and resuscitated cardiac arrest, occurred. This particular information could act as a reassurance for everyday clinical practice. Thus, for patients with LVNC diagnosis but otherwise no signs of structural or functional cardiac damage detected in CMR, prognosis would be expected to be favorable. LVNC is merely an appearance of the ventricle that needs to be interpreted together with additional data in a specific clinical context. LVNC may be isolated when no additional cardiac pathology is seen and often incidentally detected, and it can also be reversible, as in athletes after detraining. In these circumstances, the term “hypertrabeculation” rather than “LVNC cardiomyopathy” should be preferred. Then again, it can also be seen in patients with clinical and diagnostic evidence of NICM, such as in the context of dilated cardiomyopathy, hypertrophic cardiomyopathy, and so on. Therefore, when LVNC pattern is found, the term “cardiomyopathy” should be used with caution, and clinical judgment should be exercised, not just strict definitions or plain diagnostic criteria.
This evidence highlights the important role of CMR in LVNC, not only regarding diagnosis but above and beyond, regarding risk stratification and future medical treatment and management. CMR’s ability to provide an accurate and reproducible assessment of ventricular volumes and systolic function as well as to detect macroscopic areas of myocardial fibrosis could act as a diagnostic gatekeeper. In patients with normal global systolic function and absence of myocardial fibrosis, physicians could be reassured even in the presence of significant LVNC, and a watchful waiting strategy would be appropriate. In contrast, when myocardial fibrosis with or without impaired global systolic function is detected in patients with LVNC, a high level of suspicion for possible future cardiac events should be considered and patients therefore followed and treated accordingly as all other patients with NICM regardless of the presence of LVNC. Most importantly and on the basis of results of this meta-analysis, the sole evidence of LVNC without additional CMR signs of cardiac disease would suggest prudence in defining subjects as having cardiomyopathy, and specific medical treatment should be discouraged.
Some important limitations of this meta-analysis need to be specified. We must first of all underline the fact that different criteria were used among studies for LVNC diagnosis. To make the meta-analysis population uniform, we decided to consider LVNC diagnosis positive regardless of the criterion used. In 3 of 4 studies, the Petersen criteria were used and selected for analysis. Moreover, and given this limitation, it is not possible to investigate a possible association between the extent of trabeculations and clinical outcomes. Additionally, we must acknowledge that results and their interpretation are valid only for the adult population, because studies considering pediatric patients were deliberately excluded. Evidence exists on LVNC in pediatric patients, in whom excessive trabeculations can be seen in various pathologies, such as Barth syndrome (31). It is likely that LVNC shares the same appearance of 2 different and sometimes overlapping cardiac diseases: a form secondary to interruption of the myocardial compaction process during embryogenesis, with an early diagnosis during childhood, and the epiphenomenon of NICM with sometimes an associated pressure or volume overload physiopathology. This hypothesis is supported by the fact that LVNC in childhood has a different and more aggressive presentation than LVNC diagnosed in adulthood. Shi et al. (32) recently published the results of the National Australian Childhood Cardiomyopathy Study showing that in their pediatric population of children with LVNC, freedom from death or transplantation was 48% after 10 years of follow-up and that long-term outcomes of children with LVNC were worse than those of matched children with dilated cardiomyopathy in the absence of LVNC, data that appear contradictory to our population analysis consisting of adults with LVNC.
Patients with isolated LVNC and absence of LGE have a better prognosis than those with LVNC and presence of LGE. Patients with LVNC share the same prognosis compared with those without LVNC, matched for LVEF. When LGE is negative and global systolic function is preserved, no hard cardiac events are to be expected. CMR in patients with LVNC should be considered to allow appropriate risk stratification and identification of patients in need of closer follow-up and more aggressive medical treatment.
COMPETENCY IN MEDICAL KNOWLEDGE: In a meta-analysis of LVNC of the 4 largest available CMR studies, no hard cardiac events, such as cardiac death, appropriate ICD firing, cardiac transplantation, and LVAD implantation, were found among patients with LVNC diagnoses when LGE was absent and global systolic function preserved.
TRANSLATIONAL OUTLOOK: The presence of LV hypertrabeculation is not necessarily evidence of cardiomyopathy. For LVNC, additional criteria such as LV systolic impairment and LGE need to be considered for diagnostic and prognostic purposes. Future multicenter, prospective studies are warranted to confirm CMR’s role in LVNC risk stratification.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- confidence interval
- cardiac magnetic resonance
- heart failure
- implantable cardioverter-defibrillator
- late gadolinium enhancement
- left ventricular
- left ventricular assist device
- left ventricular ejection fraction
- left ventricular noncompaction
- nonischemic cardiomyopathy
- odds ratio
- sudden cardiac death
- Received September 21, 2018.
- Revision received December 18, 2018.
- Accepted December 20, 2018.
- 2019 American College of Cardiology Foundation
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