Exercise contractility reserve assessed by signal-morphology impedance cardiography identifies responders to CCR in HFrEF

Background Comprehensive cardiac rehabilitation (CCR) improves functional capacity in many patients with heart failure with reduced ejection fraction (HFrEF), yet the mechanisms underlying heterogeneous responses remain unclear. Signal-Morphology Impedance Cardiography (SM-ICG) provides continuous, noninvasive assessment of exercise hemodynamics. Our previous work in this same CCR CHF cohort identified CTi exercise profiles at baseline as predictors of training response. This study examined whether SM-ICG parameters, particularly contractility reserve (CTi_res), behave as markers of CCR response. Methods Seventy-three HFrEF patients completing a 3–4-week CCR programme underwent pre- and post-training CPET with SM-ICG. Responders (R) were defined as achieving ≥3.5 mL·min−¹·kg−¹ increase in V̇O2peak or ≥24 W in Wpeak. SM-ICG variables included cardiac index (CI), heart rate, stroke volume index (SVi), systemic vascular resistance index (SVRi), CTi at rest and peak (CTi_rest, CTi_max), and CTi_reserve (CTi_res = CTi_max – CTi_rest), LV preload (early diastolic filling ratio, EDFR). Baseline values, post-CCR values, and training-induced changes were compared. Results Thirty-two patients (44%) were responders. CTi_rest, CTi_max and CTi_res did not differ between groups at baseline (p > 0.40). Apart from slightly higher CI_rest and lower SVRi_max in R, baseline hemodynamics were similar. After CCR, R demonstrated significant increases in CI_max, CI_res and SVi_res, while NR showed no central hemodynamic improvement. Contractile adaptations differed markedly: CTi_max increased by +64.3 ± 78.2 AU in R vs. –13.2 ± 52.7 AU in NR, and CTi_reserve increased by +51 ± 53% in R vs. –35 ± 44% in NR, with 94% of R increasing CTi_reserve and 93% of NR decreasing it (p < 0.001). No significant group differences were observed for changes in (a-v̅)O2diff or SVRi. Conclusion In HFrEF patients undergoing CCR, CTi_reserve is not a baseline discriminator, but its direction and magnitude of change with training may constitute a powerful marker of hemodynamic adaptation and CCR response. Responders display substantial gains in exercise contractile reserve, whereas non-responders show stable or declining CTi_reserve despite training. These findings support integrating SM-ICG into exercise testing to refine mechanistic evaluation, stratify CCR response, and guide personalised CCR prescriptions.