Background A hybrid approach to chronic total occlusion (CTO) percutaneous coronary intervention (PCI) prioritizing and combining all available crossing techniques was developed to optimize procedural efficacy, efficiency, and safety, but there is limited published data on its outcomes. Methods We examined the procedural techniques and outcomes of 1,036 consecutive CTO PCIs performed using a hybrid approach between 2012 and 2015 at 11 US centers. Results Mean age was 65±10 years and 86% of the patients were men, with a high prevalence of diabetes mellitus (43%) and prior coronary artery bypass graft surgery (34%). Most target CTOs were located in the right coronary artery (59%), followed by the left anterior descending artery (23%) and the circumflex (19%). Dual injection was used in 71%. Technical success was achieved in 91% and a major procedural complication occurred in 1.7% of cases. The final successful crossing technique was antegrade wire escalation in 46%, antegrade dissection/re-entry in 26%, and retrograde in 28%. The initial crossing strategy was successful in 58% of the lesions, whereas 39% required an additional approach. Overall, antegrade wire escalation was used in 71%, antegrade dissection/re-entry in 36%, and the retrograde approach in 42% of procedures. Median contrast volume, fluoroscopy time, and air kerma radiation dose were 260 (200–360) ml, 44 (27–72) min, and 3.4 (2.0–5.4) Gray, respectively. Conclusion Application of a hybrid approach to CTO crossing resulted in high success and low complication rates across a varied group of operators and hospital practice structures, supporting its expanding use in CTO PCI.

SignificanceThe beneficial effects of LXR-pathway activation have long been appreciated, but clinical application of synthetic LXR ligands has been limited by coactivation of SREBP1c and consequent hypertriglyceridemia. Natural LXR ligands such as desmosterol do not promote hypertriglyceridemia because of coordinate down-regulation of the SREBP pathway. Here we demonstrate that synthetic desmosterol mimetics activate LXR in macrophages both in vitro and in vivo while suppressing SREBP target genes. Unexpectedly, desmosterol and synthetic desmosterol mimetics have almost no effect on LXR activity in hepatocytes in comparison with conventional synthetic LXR ligands. These findings reveal cell-specific differences in LXR responses to natural and synthetic ligands in macrophages and liver cells that provide a conceptually new basis for future drug development.

Background We sought to examine the efficacy and safety of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) using the retrograde approach. Methods and Results We compared the outcomes of the retrograde vs. antegrade-only approach to CTO PCI among 1,301 procedures performed at 11 experienced US centers between 2012 and 2015. Mean age was 65.5±10 years and 84% of the patients were men with a high prevalence of diabetes mellitus (45%) and prior coronary artery bypass graft surgery (CABG, 34%). Overall technical and procedural success rates were 90% and 89%, respectively, and in-hospital major adverse cardiovascular events (MACE) occurred in 31 patients (2.4%). The retrograde approach was employed in 539 cases (41%), either as the initial strategy (46%) or after a failed antegrade attempt (54%). As compared with antegrade-only cases, retrograde cases were significantly more complex, both clinically (prior CABG prevalence: 48% vs. 24%, p<0.001) and angiographically (mean J-CTO score: 3.1±1.0 vs. 2.1±1.2, p<0.001) and had lower technical success (85% vs. 94%, p<0.001) and higher MACE (4.3% vs. 1.1%, p<0.001) rates. On multivariable analysis, the presence of suitable collaterals, no smoking, no prior CABG and left anterior descending artery target vessel were independently associated with technical success using the retrograde approach. Conclusions The retrograde approach is commonly used in contemporary CTO PCI, especially among more challenging lesions and patients. While associated with lower success and higher MACE rates in comparison to antegrade-only crossing, retrograde PCI remains critical for achieving overall high success rates.