Apical hypertrophic cardiomyopathy in a real-world cohort: phenotypic features, sudden cardiac death risk assessment and clinical outcomes

Introduction

Hypertrophy cardiomyopathy (HCM) is a complex entity with heterogeneous phenotypic expression. Apical HCM remains underrepresented in contemporary studies, limiting understanding of its phenotypic features and clinical outcomes.

Purpose

To characterize and compare apical and non-apical HCM phenotypes, including sudden cardiac death (SCD) risk scores performance and disease-related outcomes.

Methods

Retrospective single-center analysis including HCM patients (pts) followed at a specialized HCM clinic. HCM mimics were excluded. Pts were classified as apical vs non-apical HCM. Adverse cardiovascular (ACV) events included death, major CV events and urgent visits. Clinical, imaging and genetical data were collected via medical records review.

Results

A total of 165 HCM pts were included - 32 (19.4%) with apical HCM and 133 (80.6%) with non-apical HCM (predominantly asymmetrical septal).

Demographic characteristics were similar – 52% male (p=0.340), mean age at diagnosis 52 ± 20 years (p=0.138), 50.9% through routine CV or familial cascade screening (p=0.988), though 70% had no family history of HCM (p=0.175).

Genetic testing was performed in 81.2% (p=0.082), with 44.4% classifying as genotype-positive (p=0.282), with predominantly sarcomeric variants (81.4%; p=1).

Baseline left ventricle (LV) systolic function was preserved in 95.2% (p=0.828). Non-apical HCM pts showed higher prevalence of systolic anterior motion of mitral valve leaflet (26.1% vs 0%, p<0.001) and LV outflow tract obstruction (LVOTO; 29.6% vs 3.3%, p=0.003). Apical HCM pts had lower LV maximal wall thickness (MWT; 15 ± 4 mm vs 18 ± 5 mm, p=0.027) and lower E/A ratio (0.9±0.28 vs 1.1±0.64, p=0.025). Late gadolinium enhancement burden was similar across groups (17±15%, p=0.865).

Over a median follow-up of 7 (IQR 9) years, atrial fibrillation occurred in 30% (p=0.402), with a trend toward earlier onset in apical HCM (4±6 years vs 9±12 years, p=0.071). 8.9% had new onset of HF with reduced ejection fraction, more frequent in non-apical HCM (10.2% vs 3.4%, p=0.469).

ACV events occurred in 31.5% (p=0.813), with no differences in incidence nor the time to its occurrence (median survival 17 years, log-rank p=0.295).

The European Society of Cardiology (ESC) HCM 5-year sudden cardiac death (SCD) risk score was significantly higher in non-apical HCM (2±1.7 vs 1.6±0.9, p=0.008). Receiver operating characteristic analysis showed good discrimination for sustained ventricular arrhythmias in non-apical HCM but poor in apical HCM (figure 1), with a significant difference in areas under de curve (AUCs; ΔAUC = 0.49, 95% CI −0.84 to −0.13; p = 0.007).

Conclusion

In this real-world cohort, apical HCM was associated with LVOTO and LV MWT but a non-despicable burden of ACV events. The ESC risk score showed significantly poor performance in this subgroup, highlighting important phenotype-specific limitations and the need for improved disease management.For image description, please refer to the figure legend and surrounding text.