Greiten, Lawrence E.

Introduction: We compared outcome of repeat CABG (RCABG) and PCI in patients with previous CABG. Hypothesis: RCABG may improve survival versus PCI. Methods: From 1993 through 2009, 3,058 patients underwent revascularization after previous CABG. RCABG patients (n=530) were grouped by the use of arterial grafts (n=396), or saphenous vein grafts (SVG; n=134). At previous CABG, 37% of RCABG patients received IMA graft. PCI patients (n=2,528) were grouped into balloon angioplasty (BA; n=491), bare metal stent (BMS; n=1,267), and drug-eluting stent (DES; n=769). PCI patients were further stratified by the treated target into native coronary artery (n=1,637), bypass grafts (n=674), or both (n=216). Propensity score analysis matched 287 patients. Results: RCABG had increased 30-day mortality compared with PCI (HR=3.92; 95% CI, 2.25-6.84; P <.001) in multivariable analysis, while in propensity matched analysis it did not ( P =.09). Overall survival, however, was greater for RCABG compared with PCI in multivariable analysis (HR=0.70; 95% CI, 0.59-0.83; P <.001), as well as in propensity matched analysis (10-year survival rates were 52% vs 37%, respectively [ P =.005]). Compared with RCABG, PCI involving bypass grafts had increased mortality (HR, 1.39; 95% CI, 1.09-1.78; P =.008), whereas PCI targeting only the native coronaries did not (HR, 1.12; 95% CI, 0.85-1.47; P =.43); BMS patients had increased mortality (HR, 1.34; 95% CI, 1.06-1.68; P =.013), but DES did not (HR, 1.28; 95% CI, 0.77-2.12; P =.35). At RCABG, 318 patients (60%) received an IMA graft and late survival was similar to those receiving SVG; The use of IMA in previous CABG was associated with improved survival (HR=0.82; 95% CI, 0.72-0.92; P <.001]. Conclusions: Long-term survival after previous CABG is improved with RCABG compared to PCI, especially when PCI involves bypass grafts. There is no difference in long-term survival between RCABG using arterial grafts vs SVG only if IMA is used in either previous or RCABG.

Cardiovascular calcification is often an active process involving re-differentiation of cells to an osteoblast-like phenotype, and is strongly associated with aging. Sirtuins are histone and protein deacetylases that play a critical role in a number of age-related diseases, and SIRT6-deficient mice have the most profound progeroid phenotype. The role of SIRT6 in the regulation of cardiovascular calcification, however, is poorly understood. We hypothesized that age-related reductions in sirtuins promote osteogenic differentiation in cells from aortic valve and aorta. We used aortic valve interstitial cells isolated from SIRT6-deficient mice, pigs, or humans, and vascular smooth muscle cells from mouse aorta to determine whether osteogenic differentiation of cardiovascular cells is regulated by SIRT6 levels. In line with our hypothesis, we found increased p-SMAD1/5/8 levels in cells from SIRT6-deficient aortic valve and aorta. Second, global SIRT inhibition with NAD+-depletion increased histone acetylation and protein levels of the osteogenic proteins Sp7 and Runx2. Third, inhibition of SIRTs enhanced the transcriptional responses of Sp7 and Runx2 when cells were treated with BMP2. Fourth, knockdown of SIRT6 in mouse and human aorta and aortic valve cells by RNA interference increased Sp7 expression. Finally, chronic pharmacological inhibition of SIRTs promoted calcified nodule formation and calcium deposition in cultured mouse/swine aortic valve cells. Collectively, our data suggest that reductions in SIRT6 levels favor amplification of pro-osteogenic signaling and osteogenic differentiation of cardiovascular cells and promote the formation of calcified nodules in vitro . These data also suggest that sirtuin re-activation may be a useful therapy to slow initiation and/or progression of cardiovascular calcification in vivo.

Purpose: To describe the technical aspects of a thoracoabdominal aortic aneurysm (TAAA) repair using a patient-specific fenestrated-branched stent-graft. Technique: The technique is demonstrated in a 69-year-old man with a 6.2-cm asymptomatic type III TAAA. A patient-specific fenestrated-branched stent-graft was designed with 2 down-going directional branches for the celiac and superior mesenteric arteries and 2 reinforced fenestrations for the renal arteries. The procedure was performed under general anesthesia and included sequential stenting of the celiac, superior mesenteric, and bilateral renal arteries. The patient was discharged from the hospital on postoperative day 5 with no complications. Follow-up computed tomography angiography demonstrated exclusion of the aneurysm and patent target vessels at 12-month follow-up. Conclusion: This article and illustrated video highlight the steps for procedure planning and implantation of fenestrated and branched endografts. As these techniques continue to evolve, outcomes are expected to be equivalent or improved as compared to those of long-established open repair.