Inter-ethnic differences in valve morphology, valvular dysfunction, and aortopathy between Asian and European patients with bicuspid aortic valve.

Background: Transcatheter aortic valve replacement (TAVR) has been shown safe and feasible in patients with bicuspid aortic valve (BAV) morphology. Evaluation of inter-ethnic differences in valve morphology and function and aortic root dimensions in patients with BAV is important for the worldwide spread of this therapy in this subgroup of patients. Comparisons between large European and Asian cohorts of patients with BAV have not been performed, and potential differences between populations may have important implications for TAVR. Aim: The present study evaluated the differences in valve morphology and function and aortic root dimensions between two large cohorts of European and Asian patients with BAV. Methods and results: Aortic valve morphology was defined on transthoracic echocardiography according to the number of commissures and raphe: type 0 = no raphe and two commissures, type 1 = one raphe and two commissures, type 2 = two raphes and one commissure. Aortic stenosis and regurgitation were graded according to current recommendations. For this study, aortic root dimensions were manually measured on transthoracic echocardiograms at the level of the aortic annulus, sinus of Valsalva (SOV), sinotubular junction (STJ), and ascending aorta (AA). Of 1427 patients with BAV (45.2 ± 18.1 years, 71.9% men), 794 (55.6%) were Europeans and 633 (44.4%) were Asians. The groups were comparable in age and proportion of male sex. Asians had higher prevalence of type 1 BAV with raphe between right and non-coronary cusps than Europeans (19.7% vs. 13.6%, respectively; P < 0.001), whereas the Europeans had higher prevalence of type 0 BAV (two commissures, no raphe) than Asians (14.5% vs. 6.8%, respectively; P < 0.001). The prevalence of moderate and severe aortic regurgitation was higher in Europeans than Asians (44.2% vs. 26.8%, respectively; P < 0.001) whereas there were no differences in BAV with normal function or aortic stenosis. After adjusting for demographics, comorbidities, and valve function, the dimensions of the aortic annulus [mean difference 1.17 mm/m2, 95% confidence interval (CI) 0.96-1.39], SOV (mean difference 1.86 mm/m2, 95% CI 1.47-2.24), STJ (mean difference 0.52 mm/m2, 95% CI 0.14-0.90) and AA (mean difference 1.05 mm/m2, 95% CI 0.57-1.52) were significantly larger among Asians compared with Europeans. Conclusions: This large multicentre registry reports for the first time that Asians with BAV showed more frequently type 1 BAV (with fusion between right and non-coronary cusp) and have larger aortic dimensions than Europeans. These findings have important implications for prosthesis type and size selection for TAVR.

Comparison of risks and clinical predictors of contrast-induced nephropathy in patients undergoing emergency versus nonemergency percutaneous coronary interventions.

BACKGROUND: Contrast nephropathy (CIN) increases adverse clinical outcomes. We examine risks and clinical predictors of CIN in patients undergoing percutaneous coronary intervention (PCI) and effectiveness of prophylactic therapy. METHODS: A cohort of 8,798 patients who underwent PCI from May 2000 to April 2008 was enrolled. We divided patients into 3 groups. A: STEMI patient undergoing primary PCI; B: UA/NSTEMI patients undergoing early PCI; C: Patients without MI undergoing elective PCI. Pre-PCI saline hydration was given to group B and C if baseline glomerular filtration rate (GFR) <60 ml/min/1.73 m². RESULTS: Mean age was 57.4 years; 35.9% was diabetics. Incidence of CIN were 12.0%, 9.2%, and 4.5%, in group A, B and C (P = <0.0005). CIN correlated with higher mortality (15.5% vs. 1.3%, P < 0.0005) at 1 month. The important predictors of CIN were age >70, female gender, anemia, low systolic BP < 100 mmHg, high creatinine kinase level, abnormal LVEF, baseline renal impairment, MI and insulin dependent diabetes. Incidence of CIN in patients with GFR >60 were 8.2%, 9.2%, and 4.3% in group A, B, and C respectively (p < 0.0005). Incidence of CIN in patients with GFR = 30-60 were 19.1%, 4.5%, and 2.4% (p < 0.0005) and in patients with GFR < 30 were 34.4%, 40.0%, and 25.9% (p = 0.510). CONCLUSIONS: Pre-hydration prophylaxis was effective in preventing CIN in mild renal impaired patients (GFR 30-60) but are less so in more severely renal impaired patients (GFR < 30). STEMI patients undergoing primary PCI regardless of baseline GFR were at high risk. Accelerated prophylactic regime can be considered in this cohort.

Autologous skeletal myoblasts transduced with a new adenoviral bicistronic vector for treatment of hind limb ischemia.

OBJECTIVE: We aimed to achieve angiogenic synergism between human vascular endothelial growth factor 165 (VEGF 165 ) and angiopoietin-1 (Ang-1) using a new adenoviral bicistronic vector concurrently with cell therapy to repair an ischemically damaged hind limb in a rabbit model. METHODS: Rabbit autologous primary skeletal myoblasts were isolated and labeled with retrovirally transduced LacZreporter gene, 4,6-diamidino-2-phenylindole (DAPI), and 5-bromo-2'-deoxyuridine (BrdU). Hind limb ischemia was created in 48 female New Zealand White rabbits by means of femoral artery ligation at 8 different places, and was assessed at angiography. Animals were randomized to receive intramuscular injection of either Dulbeco's Modified Eagle Medium (DMEM;group 1, n = 8), nontransduced myoblasts (group 2, n = 10), or myoblasts transduced with Ad-Null (group 3, n = 10), Ad-VEGF (group 4, n = 10), or Ad-Bicis (group 5, n = 8). Six weeks after treatment neovascularization in the limb was assessed at angiography. The animals were euthanized, and tissue was harvested for histologic study. RESULTS: Extensive transplanted myoblast survival was observed in all cell-transplanted groups, as visualized with DAPI, BrdU, and LacZ staining. Angiographic blood vessel count revealed enhanced neovascularization in group 5 (25.14 +/- 5.14) compared with group 4 (13.62 +/- 4.52), group 3 (6.09 +/- 0.09), group 2 (4.67 +/- 3.49), and group 1 (3.18 +/- 7.76). Immunostaining for von Willebrand factor confirmed significantly increased capillary density ( P < .01) at high-power microscopic field in group 5 (19.04 +/- 1.59) compared with group 4 (15.31 +/- 1.55), group 3 (6.53 +/- 0.97), group 2 (5.69 +/- 0.51), and group 1 (3.03 +/- 0.20). CONCLUSION: Simultaneous expression of VEGF and Ang-1 from bicistronic vector transduced skeletal myoblasts potently stimulated enhanced functional neovascularization in a rabbit model of limb ischemia.