Left Ventricular Non-Compaction, Trait Or Cardiomyopathy

Abstract Background The diagnosis of cardiac hypertrabecularization has increased considerably in recent years. Whether or not the non-compaction is a pathological condition or a physiological trait is still highly debated. We performed a meta-analysis and systematic review on more than 7,000 adult individuals with left ventricular non-compaction to provide a comprehensive overview on its clinical outcome as well as its genetic background. Methods We first retrieved PubMed/Medline literatures in English language between 2000 to 2018 on clinical outcome and genotype of patients with non-compaction. Altogether, 35 studies with non-compaction cardiomyopathy patients passed the selection criteria and were extensively reviewed and meta-analyzed. Furthermore, we summarized the results of 8 major studies, which investigated the non-compaction in athletes, pregnant women, patients with sickle cell disease, or in individuals from population-based cohorts. Results About 60% of the patients with left-ventricular non-compaction cardiomyopathy were male. The diagnosis was mostly made in the mid of patients' 5th decade. Seven percent of patients had congenital heart diseases (CHD) including atrial/ventricular septum defect or Ebstein anomaly. Around 25% of the patients had positive family history for cardiomyopathy. Frequent phenotypic manifestations were heart rhythm abnormalities including conduction disease (26%), supraventricular tachycardia (17%), and sustained or non-sustained ventricular tachycardia (18%). Neuromuscular disease was a reported comorbidity with a mean frequency of 5%. Three important outcome measures including systemic thromboembolic events (9%), heart transplantation (4%), and adequate ICD therapy (15%) were reported. The genetics of non-compaction cardiomyopathy showed TTN to be the most frequently mutated gene (11%), followed by MYH7 (9%), MYBPC3 (5%), and CASQ2, LDB3 (3% each). TPM1, MIB1, ACTC1, and LMNA mutations had an average frequency of 2% each followed by PLN, HCN4, TAZ, DTNA, TNNT2, and RBM20 (1% each). Eight studies that investigated the occurrence of non-compacted myocardial regions in apparently heart healthy individuals applied different, established imaging-based diagnostic criteria for non-compaction and could confirm its presence in a wide range of 1.3% to 37%. Conclusion This meta-analysis summarizes the clinical presentation of left ventricular non-compaction in a large dataset and indicates that its presence often leads to unfavourable outcome, but can also be observed in heart healthy individuals. Multimodal diagnostic workflows are needed for comprehensive understanding of these individuals and for distinguishing between benign morphological trait and manifest cardiomyopathy.