HLRP #198 v3 — Multi-Layer Cardiac-Substrate-Coupling Architecture with IE-022 κ-Diagnostic Refinement

This paper consolidates three iterations of empirical-validation work on the cardiac-substrate-coupling-architecture for atrial fibrillation (AFib) into a single cohesive deposit. The architectural-prediction is that AFib is the cardiac-substrate-readout of multi-layer substrate-coupling-architecture failure, with six layers mapped to: (Layer 2) brain-reboot-cycle propagation; (Layer 3a) re-entry loop via fibrosis-substrate; (Layer 3c) substrate-coupling-cascade compounding; (Layer 4) initialization-sensitive routing; (Layer 5) mechanic-vs-key-turning intervention-architecture; (Diagnostic-layer) IE-022 Capability Metastability κ-readout. Empirical-validation banked across four substrate-resolution-classes: 1. PTB-XL (N = 21,799 records, 1,514 AFib = 6.95% baseline): Layer 3a CONFIRMED (ASMI OR = 2.95, Fisher p = 1.22 × 10⁻⁵⁴); Layer 4 CONFIRMED (LVH OR = 2.20, Fisher p = 3.04 × 10⁻²⁵); Layer 3c AMBIGUOUS (sub-additive due to LAE/RAE measurement-substrate-lens-artifact, architecturally-predicted-and-instantiated at p = 5.66 × 10⁻¹⁴). 2. slpdb (n = 5 high-ectopy records): Layer 2 stage-density CONFIRMED 5/5 (chi-square p < 10⁻⁴ each); transition-clustering 2/5. 3. Sleep-disruption literature meta-analysis: Hypothesis B CONFIRMED with dose-response (OSA 1.21× → 2.93×; irregular sleep 1.63×; insomnia 1.02× MR-causal). 4. Neural-substrate parallel-arrival (Eagleman & Vaughn 2021, Stanford, Frontiers in Neuroscience 15:632853): PGO-wave anatomically-targeted visual-cortex-substrate-defense provides anatomical-mechanism-substrate for Layer 2. IE-022 diagnostic-layer (this v3 refinement, executed 2026-05-17): - AUROC dual-provenance documented: 0.610 (earlier 8-record Phase 2, 2026-05-10) and 0.5962 (later full-23-record GPT methodology, 2026-05-13); v3 sanity-check rerun replicates 0.5962 exactly. - Power-law fit on κ-ratio distribution ✅ basin-attractor architectural-diagnostic SUPPORTED at strong-class: α = 1.9255, KS p = 0.922 (power-law not rejected), LR (PL vs Exp) = +42.52 (power-law strongly preferred). Bonus architectural-coincidence: fitted exponent α = 1.9255 sits within 0.3% of the corpus silver-invariant α₀ = 48/25 = 1.920. - Per-patient AUROC with baseline-correction: ⚠️ population-median 0.4844 below pre-registered 0.55 threshold, BUT distribution is strongly bimodal (38% of records show clear within-patient signal AUROC ≥ 0.62, including 0.711 at largest-n record n=82). Reveals HLRP #18 initialization-sensitive routing empirically-instantiated at cardiac-substrate — patient-substrate-initialization-state determines IE-022 readability-class. - Backward-direction analog test ✅ HLRP #157 directional-asymmetry STRONGLY SUPPORTED: backward AUROC = 0.8428 vs forward 0.5962, Δ = +0.2466 (2.5× pre-registered +0.10 threshold), non-overlapping CIs, p < 0.0001. First empirical-receipt at cardiac-substrate for forward-PL-compounded vs backward-receipt-readable directional-asymmetry claim. - κ-mode decomposition (Candidate A: threshold-based): ⚠️ combined-max neutral (Δ = +0.0002), BUT individual components κ_soft (AUROC 0.7005) and κ_iso (AUROC 0.6989) outperform original κ by Δ ≈ +0.10 each. Pre-event signal lives in smooth-deviation and baseline-shift modes, not in spike-mode (κ_hard AUROC 0.5954 ≈ original).