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Introduction Lateral or posteriolateral coronary vein has been considered the optimal location of left ventricular (LV) lead placement for cardiac resynchronisation therapy (CRT). However, the long-term clinical outcomes of CRT based on LV lead location have not been sufficiently addressed. Methods Seven hundred and eighteen CRT-P/CRT-D recipients from Jan 2002 to Dec 2008 were studied. At the CRT implant, the LV lead placement was prioritised as posterolateral/lateral (PL, 50%), anterior lateral (AL, 31%), anterior interventricular (AI, 12%) or middle cardiac veins (MC, 7%). NYHA class and echocardiography were assessed before and after CRT. Clinical outcomes of CRT were compared among 4 LV lead locations. Results Patient baseline demographics, except the gender (P=0.03), were similar among four groups. After CRT, the improvement in NYHA class, LV ejection fraction (EF), and LV diastolic diameter were significantly improved comparably across four LV lead locations (table). The increase in LVEF by >5% were 46%, 47%, 41% and 42% in PL, AL, AI and MC groups (p=0.87). Conclusion The present study suggests that LV lead positioned in the alternative coronary veins, other than posteriolateral or lateral location, achieve comparable benefit in improvement of HF symptoms, and LV function after CRT. Table Comparison of clinic outcomes before and after CRT in different LV lead locations Lateral vein (N=359) Anterolateral vein (N=226) middle cardiac vein (N=49) anterior interventricular vein (N=84) Pre-CRT Post-CRT Pre-CRT Post-CRT Pre-CRT Post-CRT Pre-CRT Post-CRT NYHA 3.02±0.46 2.34±0.81* 2.92±0.53 2.34±0.89* 3.10±0.45 2.70±0.85* 2.98±0.52 2.43±0.86* LVEF (%) 23.57±7.28 30.82±11.67* 24.19±7.96 30.44±12.06* 24.97±7.62 30.72±11.43* 22.45±7.25 28.40±11.73* LVEDD (mm) 65.71±9.12 63.00±9.73* 65.79±8.87 63.88±9.88* 65.39±9.32 62.61±10.25* 68.48±8.92 64.86±9.67* LVESD (mm) 57.91±9.89 52.83±11.68* 56.69±10.23 53.03±12.01* 56.18±11.56 52.24±13.11* 59.09±10.04 55.32±13.30 RVD (mm) 0.90±0.86 0.82±0.85 0.85±0.92 0.82±0.85 0.86±0.83 1.01±0.84 0.56±0.77 0.78±0.91 RV dysfunction 1.05±0.92 0.88±0.92* 1.03±0.93 0.93±0.91 1.06±0.97 1.06±0.90 0.74±0.86 0.79±0.96 MR (m/s) 1.54±0.78 1.30±0.75* 1.57±0.83 1.35±0.75* 1.53±0.71 1.15±0.70* 1.36±0.69 1.19±0.68 * P<0.05 compared to pre-CRT.

AbstractBackgroundBortezomib, a proteasome inhibitor used to treat multiple myeloma, has been administered (± plasma exchange ± intravenous immunoglobulin [IVIg]) in attempts to reduce antibodies against human leukocyte antigens (HLA) in sensitized patients undergoing organ transplantation. To our knowledge, bortezomib has not been investigated for its effect on natural anti‐pig antibodies. If bortezomib could reduce the production of anti‐pig antibodies, this would likely be beneficial to the outcome of pig organ grafts in primates.MethodsNine patients received bortezomib either to reduce anti‐HLA antibody levels before organ allotransplantation or to treat antibody‐mediated rejection. Patients at the Mayo Clinic (Group 1; n = 4) received bortezomib alone, whereas at the UPMC (Group 2; n = 5), this was combined with plasmaphereses ± IVIg in some cases. Anti‐pig IgM and IgG levels against wild‐type (WT) and α1,3‐galactosyltransferase gene knockout (GTKO) pig aortic endothelial cells (flow cytometry—relative mean fluorescence intensity) and anti‐Gal IgM and IgG (ELISA–OD480 nm) were measured pre‐ and post‐bortezomib therapy.ResultsMean anti‐pig IgM levels were 11.2 (WT) and 1.9 (GTKO) pre‐bortezomib treatment and 9.4 (WT: P = 0.02) and 1.7 (GTKO: P = 0.33) post‐bortezomib treatment, respectively. Mean anti‐pig IgG levels were 4.3 (WT) and 1.5 (GTKO) pre‐bortezomib treatment and 3.6 (WT: P = 0.21) and 1.4 (GTKO: P = 0.20) post‐bortezomib treatment, respectively. Mean anti‐Gal IgM and IgG levels were 0.7 and 1.1, respectively, pre‐treatment, and 0.6 (P = 0.03) and 1.1 (NS), respectively, post‐treatment. When the data were analyzed in Groups 1 and 2 separately, there were no significant differences between the pre‐ and post‐bortezomib levels of anti‐pig, anti‐non‐Gal, or anti‐Gal IgM or IgG.ConclusionsFrom this limited study, we conclude that bortezomib might reduce anti‐Gal IgM levels in primates, but, in this respect alone, is unlikely to have any significant effect on the outcome of GTKO pig organ transplantation.