Effect of Heart Failure on Long‐Term Clinical Outcomes After Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Severe Coronary Artery Disease

[Background] Heart failure might be an important determinant in choosing coronary revascularization modalities. There was no previous study evaluating the effect of heart failure on long‐term clinical outcomes after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG). [Methods and Results] Among 14 867 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013 in the CREDO‐Kyoto PCI/CABG registry Cohort‐3, we identified the current study population of 3380 patients with three‐vessel or left main coronary artery disease, and compared clinical outcomes between PCI and CABG stratified by the subgroup based on the status of heart failure. There were 827 patients with heart failure (PCI: N=511, and CABG: N=316), and 2553 patients without heart failure (PCI: N=1619, and CABG: N=934). In patients with heart failure, the PCI group compared with the CABG group more often had advanced age, severe frailty, acute and severe heart failure, and elevated inflammatory markers. During a median 5.9 years of follow‐up, there was a significant interaction between heart failure and the mortality risk of PCI relative to CABG (interaction P=0.009), with excess mortality risk of PCI relative to CABG in patients with heart failure (HR, 1.75; 95% CI, 1.28–2.42; P<0.001) and no excess mortality risk in patients without heart failure (HR, 1.04; 95% CI, 0.80–1.34; P=0.77). [Conclusions] There was a significant interaction between heart failure and the mortality risk of PCI relative to CABG with excess risk in patients with heart failure and neutral risk in patients without heart failure

Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors

Smoldering inflammation often increases the risk of progression for malignant tumors and simultaneously matures myeloid dendritic cells (mDC) for cell-mediated immunity. PolyI:C, a dsRNA analog, is reported to induce inflammation and potent antitumor immune responses via the TLR3/TICAM-1 and MDA5/IPS-1 pathways in mDC to drive activation of NK cells and cytotoxic T lymphocytes. Here, we found that intraperitoneal or subcutaneous injection of polyI:C to 3LL tumor-implant mice resulted in tumor regression by converting tumor-supporting macrophages (Mf) to tumor suppressors. F4/80+/Gr1- Mf infiltrating the tumor respond to polyI:C to rapidly produce inflammatory cytokines and thereafter accelerate M1 polarization. TNF-α was increased within 1 hour in both tumor and serum upon polyI:C injection into tumor-bearing mice followed by tumor hemorrhagic necrosis and growth suppression. These tumor responses were abolished in TNF-α-/- mice. Furthermore, F4/80+ Mf in tumors extracted from polyI:C-injected mice sustained 3LL cytotoxic activity, and this activity was partly abrogated by anti-TNF-α Ab. Genes for supporting M1 polarization were subsequently up-regulated in the tumor-infiltrating Mf. These responses were completely abrogated in TICAM-1-/- mice, and unaffected in MyD88-/- and IPS-1-/- mice. Thus, the TICAM-1 pathway is not only important to mature mDC for cross-priming and NK cell activation in the induction of tumor immunity, but also critically engaged in tumor suppression by converting tumor-supporting Mf to those with tumoricidal properties