Multi-Tissue eQTL-MR Investigation of Organ-Specific Action Preference of Salvia miltiorrhiza in the Treatment of Heart Failure Under the Theory of Meridian Tropism

• • Multi-tissue MR identified ALDH2, PDHB, and CETP with the highest VOI in heart and liver, indicating that S. miltiorrhiza's genetic causal effects are concentrated in these two organs; this aligns with the meridian tropism prediction and supports organ-directed dosing strategies in HF management. • • PRKCA exhibited strong tissue preference in lung, demonstrating that S. miltiorrhiza target genes are not uniformly distributed across organs; this pulmonary signal may explain ancillary respiratory benefits observed in HF patients with comorbid pulmonary congestion. • • CASP7 showed a directional MR effect toward reduced HF risk and was significantly downregulated in HF transcriptomic data (p < 0.05), establishing it as a cross-organ protective candidate; its consistent direction across heart, liver, and lung suggests a shared anti-apoptotic mechanism amenable to pharmacological activation. • • The VOI framework quantified organ-specific contributions, with heart and liver VOI values exceeding those of kidney and lung; this metric provides a reproducible threshold for prioritizing target organs in future meridian tropism studies and reduces reliance on subjective interpretation.