Bruce Garlick

Transcatheter aortic valve replacement is associated with comparable clinical outcomes to open aortic valve surgery but with a reduced length of in-patient hospital stay: a systematic review and meta-analysis of randomised trials

BACKGROUNDnAortic valve replacement is indicated in patients with severe symptomatic aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has evolved as a potential strategy in a growing proportion of patients in preference to surgical aortic valve replacement (SAVR). This meta-analysis aims to assess the differential outcomes of TAVR and SAVR in patients enrolled in published randomised controlled trials (RCTs).nnnMETHODSnA systematic literature search of Cochrane Library, EMBASE, OVID, and PubMed MEDLINE was performed. Randomised controlled trials of patients with severe AS undergoing TAVR compared with SAVR were included. Clinical outcomes and procedural complications were assessed.nnnRESULTSnFive RCTs with a total of 3,828 patients (1,928 TAVR and 1,900 SAVR) were analysed. There was no statistically significant difference in combined rates of all-cause mortality and stroke at 30-days for TAVR vs SAVR (6.3% vs 7.5%; OR 0.83; 95% CI: 0.64-1.08; P=0.17) or at 12 months (17.2% vs 19.2%; OR 0.87; 95% CI: 0.73-1.03; P=0.29). No statistically significant difference was seen for death or stroke separately at any time point although a numerical trend in favour of TAVR for both was recorded. Length of in-patient stay was significantly less with TAVR vs SAVR (9.6 +/- 7.7 days vs 12.2 +/- 8.8 days; OR -2.94; 95% CI: -4.64 to -1.24; P=0.0007). Major vascular complications were more frequent in patients undergoing TAVR vs SAVR (8.2% vs. 4.0%; OR 2.15; 95% CI: 1.62-2.86; P <0.00001) but major bleeding was more common among SAVR patients (20.5% vs 44.2%; OR 0.34; 95% CI: 0.22-0.52; P=<0.00001).nnnCONCLUSIONSnTranscatheter aortic valve replacement and SAVR are associated with overall similar rates of death and stroke among patients in intermediate to high-risk cohorts but with reduced length of in-patient hospital stay.

Vascular remodelling in the internal mammary artery graft and association with elevated endothelin-1 expression

Introduction: The vasoconstricting peptide Endothelin-1 (ET-1) has been associated with atherosclerotic cardiovascular disease, AAA, hypertension and hypercholesterolemia. It is known to stimulate quiescent vascular smooth muscle cells (VSMC) into the growth cycle and has been linked to intimal thickening following endothelial injury and is associated with vessel wall remodelling in salt-sensitive hypertension models. Enhanced ET-1 expression has been reported in the internal mammary artery (IMA) and was markedly higher in patients undergoing cardiac bypass surgery who were diabetic and /or hypercholesterolemic. Aims: To firstly review the histopathology of the IMA and secondly, determine the relationship between ET-1 expression in this vessel and mitogenic activity in the medial VSMC. Methods: Vessel tissue collected at the time of CABG surgery was formalin-fixed and paraffin-embedded for histological investigation. Cross sections of the left distal IMAwere stained with Alcian Blue/Verhoeff’s van Gieson to assess medial degeneration and identify the elastic lamellae and picrosirius red to determine the collagen content (specifically type I and type III). Immunohistochemistry staining was used to assess VSMC growth (PCNA label), tissue ET-1 expression, VSMC (SMCa-actin) area and macrophage/monocyte (anti-CD68) infiltration. Quantitative analysis was performed to measure the VSMC area in relation to ET-1 staining. Results: Fifty-five IMA specimens from the CABG patients (10F; 45M; mean age 65 years) were collected for this study. Fourteen donor IMAspecimens were used as controls (7F; 7M; mean age 45 years). Significant medial hypertrophy, VSMC disorganisation and elastic lamellae destruction was detected in the CABG IMA. The amount of Alcian blue staining in the CABG IMA was almost double that of the control (31.85+/14.52% Vs 17.10+/9.96%, P= .0006). Total collagen and type I collagen content was significantly increased compared with controls (65.8+/18.3% Vs 33.7 + / 13.7%, P= .07), (14.2 + /10.0% Vs 4.8 + /2.8%, P= .01), respectively. Tissue ET-1 and PCNA labelling were also significantly elevated the CABG IMA specimens relative to the controls (69.99 + /18.74%Vs 23.33 + /20.53%, P= .0001, and 37.29 + /12.88% Vs 11.06 + /8.18, P= .0001), respectively. There was mild presence of macrophages and monocytes in both CABG and control tissue. Conclusions: The IMA from CABG patients has elevated levels of type I collagen in the extracellular matrix indicative of fibrosis and was coupled with deleterious structural remodelling. Abnormally high levels of ET-1 were measured in the medial SMC layer and was associated with VSMC growth but not related to any chronic inflammatory response within the vessel wall.