Clinical, Imaging, and Genetic Characteristics of Adult Left Ventricular Noncompaction: A Single-Center Registry Study

Background: Left ventricular noncompaction (LVNC) is a heterogeneous cardiomyopathy characterized by excessive myocardial trabeculation and a variable clinical presentation. Although advances in multimodality imaging have improved diagnostic accuracy, prospective longitudinal risk stratification frameworks remain limited. Methods: This single-center registry study describes the baseline clinical, imaging, electrocardiographic, and genetic characteristics of adult patients with confirmed LVNC followed at a tertiary inherited cardiac conditions clinic, enrolled both prospectively and retrospectively. Baseline assessments included demographics, clinical history, transthoracic echocardiography (TTE), cardiac magnetic resonance imaging (CMR), electrocardiography, exercise stress testing, Holter monitoring, and genetic testing. This descriptive analysis does not include a formal time-to-event outcomes analysis, which is planned for future prospective follow-up of this cohort. Results: The cohort comprised 50 adults (34 women, 16 men; mean age at diagnosis 48.9 ± 13.4 years), enrolled prospectively (n = 38) and retrospectively (n = 12). Diagnosis was established by CMR in 80% of patients (n = 40), TTE in 18% (n = 9), and CT in 2% (n = 1). Presenting features included prior cardiac arrest (n = 3), syncope (n = 10), palpitations (n = 16), and a family history of sudden cardiac death (n = 9). Baseline TTE (available in 38 patients) showed a mean left ventricular ejection fraction (LVEF) of 51.8 ± 11.8%. CMR, available for 44 patients (88% of the cohort), confirmed LVNC in all cases, with the noncompacted-to-compacted ratio (NC:C) ranging from 2.8:1 to 6.3:1 (median 4.0:1); apical hypertrabeculation was universal, and lateral involvement was present in 72.7% (32/44) of CMR-imaged patients. Among 48 patients with electrocardiogram (ECG) data, T-wave abnormalities were present in 20.8% (10/48), left bundle branch block in 14.6% (7/48), and right bundle branch block in 6.3% (3/48). Genetic testing, performed in 32 of the 38 prospectively enrolled patients, identified pathogenic or likely pathogenic variants in 53% (17/32), most commonly in TTN (34%, 11/32); the remainder had variants of uncertain significance or no identified variant. Structured follow-up data were incomplete and variably attended, with follow-up 2 assessments available in 29 of 50 patients (58%); among those retested, LVEF remained preserved or only mildly reduced (mean 51.1% and 56% at follow-up 1 and 2, respectively). Conclusions: This single-center registry demonstrates substantial phenotypic, morphologic, and genetic heterogeneity in adult LVNC, with CMR providing the most sensitive morphologic characterization and pathogenic or likely pathogenic variants identified in approximately half of genetically tested patients. Since clinical outcome events and time-to-event analyses were not assessed in this baseline dataset, these findings are hypothesis-generating rather than prognostic. Thus, structured prospective follow-up of this cohort is needed to define arrhythmic and heart failure outcomes and to refine phenotype- and genotype-directed risk stratification. Clinical Trial Registration: NCT06024759 (https://clinicaltrials.gov/study/NCT06024759?cond=NCT06024759&viewType=Card&rank=1).