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Cardiac rehabilitation (CR) improves outcomes in heart failure, but optimal initiation timing during acute hospitalization remains undefined. We characterized the dose-response association between door-to-cardiac rehabilitation time and in-hospital outcomes, describing how this pattern appeared to differ between death and functional measures.

Using the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure database, we identified 564 830 patients hospitalized for acute heart failure (2012-2023), categorized into non-CR (n=275 454) and CR groups by door-to-cardiac rehabilitation quartiles: quartile 1 (≤1 day), quartile 2 (2-3 days), quartile 3 (4-5 days), and quartile 4 (≥6 days). Generalized propensity score-based weighting adjusted for 32 confounders. Restricted cubic splines evaluated dose-response patterns among CR recipients. The primary outcome was in-hospital death; secondary outcomes were Barthel Index at discharge and Barthel Index improvement.

All door-to-cardiac rehabilitation quartiles showed lower in-hospital death versus non-CR (adjusted odds ratios, 0.39-0.49; all P<0.001). Barthel Index at discharge was higher in quartile 1 to quartile 3 (mean difference, +3.2 to +3.8 points), with a smaller difference in quartile 4. Spline analysis revealed nonlinear associations: The mortality nadir was observed at 6.1 days, whereas functional measures showed the most favorable associations at 3.3 days. Sensitivity analyses addressing immortal time bias yielded consistent mortality results.

CR was associated with a lower in-hospital mortality rate across all timing quartiles. The association pattern appeared to differ by outcome domain: Functional measures showed more favorable associations with earlier initiation (within 2-3 days), whereas a lower mortality rate was observed across a broader window. These findings warrant prospective evaluation.