Non-Linear Size Effects and Episodic Progression in the Ascending Aorta

Predicting ascending aortic (AsAo) growth is challenging. Conventional paradigms often assume a linear and monotonic relationship between baseline size and future growth that occurs continuously-assumptions that may oversimplify biology-driven disease progression. We first evaluated whether body size-indexed baseline AsAo diameter shows a non-linear association with subsequent growth at the population-level, and second whether patient-level growth trajectories are predominantly continuous or episodic.

We performed a single-center, retrospective study (2012-2024). The Primary Cohort (n=3,315; ≥2 CT/MR scans) was used to model the relationship between baseline indexed AsAo size (Z-score) and subsequent annualized growth using multivariable linear regression and generalized additive models (GAMs), adjusting for clinical covariates. A Sub-Cohort (n=1,055; ≥4 scans) was used to classify longitudinal phenotypes as: Stable (Total Growth <2.0 mm), Stable-with-Noise (Total Growth <2.0 mm with alternating small changes), Continuous Growth (Total Growth ≥2.0 mm without a qualifying event), or Discontinuous/Episodic Growth (Total Growth ≥2.0 mm with ≥1 "growth event"). A growth event was defined as a diameter increase ≥2.0 mm within a single imaging interval or across two adjacent intervals (combined 0.5-5 years).

In the Primary Cohort, baseline Z-score demonstrated a significant non-linear (U-shaped) association with subsequent growth in the GAM (p<0.001), with higher growth at both small (Z<0) and severely dilated (Z>5) sizes. In the Sub-Cohort examining growth trajectory, the distribution was: Stable: 50.4% (532/1,055), Stable-with-Noise: 21.6% (228/1,055), Continuous: 5.4% (57/1,055), and Discontinuous/Episodic 22.6% (238/1,055). Among patients with measurable growth (Total Growth ≥2.0 mm, n=295), 81%(n=238) exhibited episodic growth and 58.3% (172/295) had a non-dilated baseline aorta (Z<2). Group differences (e.g., younger age and smaller baseline Z-scores in the Growth vs. Stable groups) were consistent across sensitivity analyses.

AsAo growth is not well described by linear, continuous assumptions. Baseline size relates to future growth in a non-linear (U-shaped) manner, and nearly one-quarter of patients exhibit discrete growth bursts separated by periods of quiescence, with episodic behavior dominating among those who enlarge. These findings support a punctuated growth paradigm and argue for re-examining surveillance intervals, risk communication, and threshold-based decision pathways in thoracic aortic disease.