Overlapping phenotype of arrhythmogenic cardiomyopathy and left ventricular hypertrabeculation: clinical characteristics and prognostic implications
L Qi, Yuxiao Hu, Kunqi Yang, Tao TianAbstract
Background
Left ventricular hypertrabeculation (LVHT) is highly heterogeneous, and the presence of concomitant arrhythmias confers a markedly poor prognosis. Although the 2023 ESC guidelines conceptualized such conditions within the non-dilated left ventricular cardiomyopathy (NDLVC) spectrum, the clinical profiles, genetic architectures, and long-term outcomes of this high-risk overlapping phenotype remain largely unknown.
Purpose
This study aimed to systematically compare the clinical characteristics and prognostic disparities between patients with the ACM-LVHT overlap phenotype and those with isolated ACM or LVHT.
Methods
We retrospectively compared consecutive ACM-LVHT overlap patients with matched isolated ACM and LVHT cohorts. The primary endpoint was major adverse cardiovascular events, a composite of all-cause mortality, heart transplantation, end-stage heart failure, and malignant ventricular arrhythmias. Secondary endpoints included end-stage heart failure, defined as heart failure-related death, heart transplantation, or ventricular assist device implantation, alongside malignant ventricular arrhythmias, encompassing sustained ventricular tachycardia, ventricular fibrillation, and sudden cardiac death. Survival was assessed using Kaplan-Meier analysis.
Results
A total of 138 patients were included (31 ACM+LVHT overlap, 80 isolated LVHT, 27 isolated ACM). Baseline characteristics and LVEF were comparable across groups. The clinical profile of the overlap cohort closely resembled isolated ACM, though they exhibited significantly smaller left atrial diameters (38.0 vs. 43.0 mm, P=0.024) and higher PVC burdens (2242.0 vs. 0.5 beats/24h, P=0.022) than isolated LVHT. Kaplan-Meier survival analysis revealed a distinct prognostic profile for the overlap phenotype. For major adverse cardiovascular events (MACE), the ACM+LVHT group showed rates comparable to isolated ACM (P=0.71) but trended towards worse outcomes compared to isolated LVHT (P=0.054). Notably, the overlap cohort was associated with the highest risk of end-stage heart failure (ESHF), facing significantly worse ESHF-free survival than both isolated LVHT (P=0.013) and isolated ACM (P=0.043). Conversely, regarding malignant ventricular arrhythmias (MVA), isolated ACM tended to have the worst outcomes compared to the overlap group (P=0.073), while the MVA risk between the overlap and LVHT groups remained similar (P=0.30).
Conclusions
Rather than a simple coexistence, the ACM and LVHT overlap emerges as a distinct clinical entity. These patients are predominantly burdened by a significantly accelerated risk of ESHF, whereas their risk of MVA appears attenuated compared to isolated ACM. These preliminary findings suggest that managing the ACM and LVHT overlap phenotype may benefit from emphasizing early heart failure optimization alongside traditional arrhythmic surveillance. Prospective clinical cohorts are warranted to validate this distinct risk profile.Figure 1