Left Ventricular Non-Compaction Cardiomyopathy: A Review of the Pathophysiology, Epidemiology, Diagnosis, Genetics,...

Left ventricular non-compaction cardiomyopathy (LVNC) is an uncommon myocardial phenotype characterized by prominent trabeculae and deep blood-filled recesses. The expanding use of cardiac magnetic resonance (CMR) has increased detection, yet uncertainty persists about whether LVNC is a distinct disease or a phenotype that overlaps with other cardiomyopathies. LVNC expression reflects the interplay among genotype, sex, ancestry, and hemodynamic load and thus serves as a model for precision cardiology. We conducted a narrative review of literature published between January 2000 and April 2025 in major databases. We included clinical studies with at least 10 patients, meta-analyses, reviews, and consensus statements addressing pathophysiology, genetics, diagnosis, prognosis, and treatment. Sarcomeric variants account for a substantial fraction of cases and connect LVNC with dilated and hypertrophic cardiomyopathies. Echocardiographic and CMR criteria identify the phenotype but blur the boundary between physiological and pathological hypertrabeculation. Fibrosis on late gadolinium enhancement and systolic dysfunction are consistently associated with worse outcomes. Current management largely adapts heart-failure strategies, including neurohormonal blockade, SGLT2 inhibitors, and implantable cardioverter-defibrillators in selected high-risk patients. Optimal care integrates clinical, imaging, and genetic information. The lack of universal diagnostic criteria highlights the need for prospective studies and consensus to standardize diagnosis and treatment. Future algorithms that combine multi-omics, quantitative imaging, and AI-based risk prediction could individualize surveillance, pharmacotherapy, and device therapy.