Decoding hypertrophic cardiomyopathy mimics: key strategies in the differential diagnosis of septal bulge

Abstract Background and Introduction Current classification for cardiomyopathies rely predominantly on imaging phenotypes. However, diagnostic criteria remain poorly defined for hypertrophic cardiomyopathy (HCM) phenocopies when no clear underlying pathological basis is evident. This diagnostic uncertainty may lead to misinterpretation of structural cardiac variant, particularly in cases of ventricular septal bulge (VSB). Study Objectives This study aimed to systematically characterise and differentiate the clinical presentation, electrocardiographic features, and advanced imaging characteristics of VSB mimicking HCM, to establish robust diagnostic criteria for this phenocopy. Methods From 1,425 consecutive patients referred for cardiovascular magnetic resonance (CMR) at our tertiary centre, we identified 76 patients with echocardiographic findings suggestive of HCM but ultimately diagnosed with isolated VSB. Exclusion criteria included any clinical or imaging evidence of secondary causes for ventricular hypertrophy. A control group of patients with definitive diagnosis of HCM was included for comparative analysis. (N=24) Results Key findings demonstrated: Morphological characteristics: -VSB patients maintained normal left ventricular wall thickness though all exhibited a prominent septal bulge, with a significant mean difference of 2 mm compared to HCM (p<0.0001) -Universal presence of prominent basal septal bulge with severe aorto-septal angulation (OR:12.66, 95%CI:2.77-57.91, p<0.0001) Functional assessment: -Systolic anterior motion (SAM) was frequently observed (OR:4.4, 95%CI:1.52-11.80) in VSB phenocopies. -84% VSB exhibited hyperdynamic ventricular function. No differences in hyperdynamia between HCM and VSB were observed. -Consistently smaller left ventricular cavity dimensions (OR:5.6, 95%CI:1.59-18.9) Tissue characterisation: -Late gadolinium enhancement (LGE) was pathognomonic for HCM (OR:31.8, 95%CI:9.31-108.7), exclusively localising to regions of maximal hypertrophy -Complete absence of LGE within the septal bulge in VSB group. Electrophysiological differentiation: -No VSB cases demonstrated the characteristic HCM ECG pattern -95% of HCM controls exhibited diagnostic ECG abnormalities Conclusions This study establishes that while VSB may mimic HCM echocardiographically, multimodal assessment combining: -Absence of cardiomyopathic ECG pattern -Characteristic CMR findings (non-hypertrophied myocardium with focal bulge and severe aorto-septal angulation but no LGE) provides a reliable diagnostic algorithm. These findings have important clinical implications for preventing misdiagnosis and unnecessary genetic testing in patients with isolated VSB.Central Figure