George Asimakopoulos’s research while affiliated with Guy's and St Thomas' NHS Foundation Trust and other places

Objectives Thrombocytopenia following Perceval aortic valve replacement has been described previously with variable outcome. Studies have lacked a robust analysis of platelet fluctuation and factors affecting it. We aimed to statistically describe the trend in thrombocyte variability as compared with conventional aortic valve replacement, and to assess predictors as well as impact on associated outcomes. Methods One hundred consecutive patients with first-time Perceval were retrospectively compared to 219 patients after Perimount Magna Ease valve replacement. The primary outcome was the serial thrombocyte count on day 0–6. Generalized estimating equations were used to analyse the data using fixed-effect models: for the effect of the post-operative day on platelet count, and random-effect models estimating both time-variant (platelets) and time in-variant variables (valve type, age, LV function, pre-op platelet level). Results Perceval patients were older (72 ± 1 vs 68 ± 1 years, p < 0.01) with higher NYHA status (3(2–3) vs 2(1–2), p < 0.001). Mean platelet count in the sutureless group was lowest on day 2 (91.9 ± 31.6 vs 121.7 ± 53.8 × 10³ µl⁻¹), and lower on day 4 (97.9 ± 44) and 6 (110.6 ± 61) compared to the conventional group (157.2 ± 60 and 181.7 ± 79) but did not result in a higher number of transfusions, bleeding or longer hospital stay (p > 0.05). Reduced platelet count was a strong predictor of red cell transfusion in the conventional (p = 0.016), but not in the sutureless group (p = 0.457). Age (Coef -1.025, 95%CI-1.649—-0.401, p < 0.001) and CPB-time (Coef 0.186, 95%CI-0.371—-0.001, p = 0.048) were predictors for lower platelet levels. Conclusion Considering the older patient profile treated with Perceval, postoperative thrombocytopenia does not impact on outcome in terms of transfusions, complications or hospital stay.

Background Rapid-deployment aortic valve replacement (RDAVR) is an alternative to conventional AVR (cAVR) for aortic stenosis. Benefits include a reduction in operative times, facilitation of minimal access surgery and superior haemodynamics compared to conventional valves. However, further evidence is required to inform guidelines, preferably in the form of propensity-matched studies that include mid-term follow-up data. Methods This was a single-centre, retrospective, propensity-matched cohort study comparing the Perceval and conventional Perimount Magna Ease valve for short- and mid-term clinical parameters and size-matched mid-term echocardiographic parameters (n = 102 in both groups) from 2014 to 2020. Data were extracted from a nationally managed dataset. Results There were no demographic differences between the matched groups. The Perceval group had shorter cross-clamp time (Perceval 62 [49–81] minutes; Perimount 79 [63–102] minutes, P < 0.001), shorter bypass time (Perceval 89 [74–114] minutes; Perimount 104 [84–137] minutes, P < 0.001), and more frequent minimally-invasive approaches (Perceval 28%; Perimount 5%, P < 0.001). Size-matched haemodynamics showed initially higher gradients in the Perceval group, but haemodynamics equalised at 12 + months. The Perceval group had a more favourable % change in the left ventricular posterior wall dimension at 2 + years (Perceval − 4.8 ± 18; Perimount 17 ± 2). Conclusions The Perceval facilitated shorter operations, which may benefit intermediate-high-risk, elderly patients with comorbidities requiring concomitant procedures. It also facilitated minimally invasive surgery. Size-matched haemodynamic performance was similar at mid-term follow-up, with the Perceval possibly better facilitating regression of left ventricular hypertrophy.

Objective This retrospective study aimed to compare the outcomes of sutureless aortic valve replacement (su-AVR) and conventional bioprosthetic sutured AVR (cAVR) in high-risk patients undergoing redo surgery. Methods A total of 79 patients who underwent redo AVR between 2014 and 2021 were included in the study. Of these, 27 patients underwent su-AVR and 52 underwent cAVR. Patient characteristics and clinical outcomes were analysed using multivariate regression and Kaplan Meier survival test. Results The groups were similar in terms of age, gender, left ventricular function, and number of previous sternotomies. In cases of isolated AVR, su-AVR had significantly lower cross clamp times than cAVR (71 vs. 86 min, p = 0.03). Postoperatively, 4 cAVR patients required pacemaker compared to zero patients in the su-AVR group. There were no significant differences between the two groups in terms of postoperative complications, intrahospital stay (median 9 days, IQR 7–20), or in-hospital mortality (1 su-AVR; 2 cAVR). The long-term survival rate was similar between the su-AVR (90%) and cAVR (92%) groups (log rank p = 0.8). The transvalvular gradients at follow-up were not affected by the type of valve used, regardless of the valve size (coef 2.68, 95%CI -3.14–8.50, p = 0.36). Conclusion The study suggests that su-AVR is a feasible and safe alternative to cAVR in high-risk patients undergoing redo surgery. The use of su-AVR offers comparable outcomes to cAVR, with reduced cross clamp times and a lower incidence of postoperative pacemaker requirement in isolated AVR cases. The results of this study contribute to the growing body of evidence supporting the use of su-AVR in high-risk patients, highlighting its feasibility and safety in redo surgeries.

Objectives Thrombocytopenia following Perceval aortic valve replacement has been described previously with variable outcome. Studies have lacked a robust analysis of platelet fluctuation and factors affecting it. We aimed to statistically describe the trend in thrombocyte variability as compared with conventional aortic valve replacement, and to assess predictors as well as impact on associated outcomes. Methods 100 consecutive patients with first-time Perceval were retrospectively compared to 219 patients after Perimount Magna Ease valve replacement. The primary outcome was the serial thrombocyte count on day 0–6. Generalized estimating equations were used to analyse the data using fixed-effect models: for the effect of the post-operative day on platelet count, and random-effect models estimating both time-variant (platelets) and time in-variant variables (valve type, age, LV function, pre-op platelet level). Results Perceval patients were older (72 ± 1 vs 68 ± 1 years,p < 0.01) with higher NYHA status (3(2–3) vs 2(1–2),p < 0.001). Mean thrombocyte count in the sutureless group was lowest on day 2 (91.9 ± 31.6 vs 121.7 ± 53.8 x10³µl− 1), and lower on day 4 (97.9 ± 44) and 6 (110.6 ± 61) compared to the conventional group (157.2 ± 60 and 181.7 ± 79) but did not result in a higher number of transfusions, bleeding or longer hospital stay (p > 0.05). Reduced platelet count was a strong predictor of red cell transfusion in the conventional(p = 0.016), but not in the sutureless group(p = 0.457). Age (Coef − 1.025, 95%CI-1.649 - -0.401,p < 0.001) and CPB-time (Coef 0.186, 95%CI-0.371 - -0.001,p = 0.048) were predictors for lower platelet levels. Conclusion Considering the older patient profile treated with Perceval, postoperative thrombocytopenia does not impact on outcome in terms of transfusions, complications or hospital stay.

Re-intervention for patients with mitral valve disease is a growing challenge. We present a 59-year-old male with a history of a congenitally bicuspid aortic valve. He had valve and root replacement for aortic regurgitation in his 30s and two subsequent sternotomies for prosthesis failure and endocarditis. After admission with acute pulmonary edema, there was persistent NYHA class II-III dyspnea. Echo showed severe (grade IV) mitral regurgitation due to the dehiscence of a 32mm mitral annuloplasty ring. The coaptation point of the leaflets was posterior to the posterior aspect of the ring. No regurgitation was observed through the ring’s central orifice, but the tissue was seen on its posterior aspect, suggesting torn posterior leaflet or healed vegetation. The left ventricle was mildly dilated, and the LVEF was 53%. The right ventricle was moderately dilated with severe functional tricuspid regurgitation with a normally functioning aortic valve prosthesis. After extensive discussion, due to his multiple previous surgeries and challenging anatomy, the patient was deemed unsuitable for surgical treatment. There is some limited registry data to support TEER as a safe and feasible alternative to surgery in this cohort. He underwent successful implantation of two clip devices in the A2/P2 and A2/P2b positions via a trans-septal approach under a general anesthetic. Femoral venous access was used. Some useful learning points relate to the challenges posed by the unusual anatomy in terms of imaging and trajectory. No MVARC complications. Postoperatively the LVEF was 55% with a mean transvalvular gradient of 5mmHg and only mild (grade I) transvalvular MR. At three months the patient reported an improvement of overall functional status. This successful case of “clip-in-ring” TEER illustrates one of the expanding indications for existing trans-catheter valvular therapies as well as the potential for creative application of TEER in helping patients with high surgical risk.

Introduction Severe aortic stenosis is a major cause of morbidity and mortality. The existing treatment pathway for transcatheter aortic valve implantation (TAVI) traditionally relies on tertiary Heart Valve Centre workup. However, this has been associated with delays to treatment, in breach of British Cardiovascular Intervention Society targets. A novel pathway with emphasis on comprehensive patient workup at a local centre, alongside close collaboration with a Heart Valve Centre, may help reduce the time to TAVI. Methods The centre performing local workup implemented a novel TAVI referral pathway. Data were collected retrospectively for all outpatients referred for consideration of TAVI to a Heart Valve Centre from November 2020 to November 2021. The main outcome of time to TAVI was calculated as the time from Heart Valve Centre referral to TAVI, or alternative intervention, expressed in days. For the centre performing local workup, referral was defined as the date of multidisciplinary team discussion. For this centre, a total pathway time from echocardiographic diagnosis to TAVI was also evaluated. A secondary outcome of the proportion of referrals proceeding to TAVI at the Heart Valve Centre was analysed. Results Mean±SD time from referral to TAVI was significantly lower at the centre performing local workup, when compared with centres with traditional referral pathways (32.4±64 to 126±257 days, p<0.00001). The total pathway time from echocardiographic diagnosis to TAVI for the centre performing local workup was 89.9±67.6 days, which was also significantly shorter than referral to TAVI time from all other centres (p<0.003). Centres without local workup had a significantly lower percentage of patients accepted for TAVI (49.5% vs 97.8%, p<0.00001). Discussion A novel TAVI pathway with emphasis on local workup within a non-surgical centre significantly reduced both the time to TAVI and rejection rates from a Heart Valve Centre. If adopted across the other centres, this approach may help improve access to TAVI.

Objective This retrospective study aimed to compare the outcomes of rapid deployment aortic valve replacement (rdAVR) and conventional bioprosthetic sutured AVR (cAVR) in high-risk patients undergoing redo surgery. Methods A total of 79 patients who underwent redo AVR between 2014 and 2021 were included in the study. Of these, 27 patients underwent rdAVR and 52 underwent cAVR. Patient characteristics and clinical outcomes were analysed using multivariate regression and Cox-survival analysis. Results The groups were similar in terms of age, gender, left ventricular function, and number of previous sternotomies. In cases of isolated AVR, rdAVR had significantly lower cross clamp times than cAVR (71 vs. 86 minutes, p = 0.03). Postoperatively, 4 cAVR patients required pacemaker compared to zero patients in the rdAVR group. There were no significant differences between the two groups in terms of postoperative complications, intrahospital stay (median 9 days, IQR 7–20), or in-hospital mortality (1 rdAVR; 2 cAVR). The long-term survival rate was similar between the rdAVR (90%) and cAVR (92%) groups (log rank p = 0.8). The transvalvular gradients at follow-up were not affected by the type of valve used, regardless of the valve size (coef 2.68, 95%CI -3.14-8.50, p = 0.36). Conclusion The study suggests that rdAVR is a feasible and safe alternative to cAVR in high-risk patients undergoing redo surgery. The use of rdAVR offers comparable outcomes to cAVR, with reduced cross clamp times and a lower incidence of postoperative pacemaker requirement in isolated AVR cases. The

Background Thoracic Aortic Aneurysm (TAA) is a disease with significant morbidity and mortality. The aneurysm is asymptomatic, and patients often present to the emergency department after a dissection. A reliable biomarker is required to diagnose the condition early to direct the patient to the appropriate services. TAA is characterised by proteoglycan accumulation which are normally found in the extracellular matrix (ECM) of the medial layer. This may be due to impaired activity of intrinsic proteases A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) 4 and 5. We aimed to find a circulating proteoglycan-based biomarker associated with abnormal material properties of the diseased aortic wall. Methods ADAMTS-generated fragment ‘versikine’, ADAMTS4, ADAMTS5, ADAMTS13 and von Willebrand Factor (vWF) were measured in the plasma of patients with TAA (n=48) and healthy controls (n=23) using Enzyme-Linked Immunosorbent Assays. Patients with connective tissue disease (CTD) and bicuspid aortic valve were excluded from the study. Mann-Whitney U test was used to compare the analyte plasma levels between the groups and Spearman Rank to test for correlation. Receiver-operator characteristics curve analysis was used to generate specificity and sensitivity values. In five patients, explanted TAA samples from surgery were processed to extract proteoglycans using 4M Guanidine HCl and purified by Diethylaminoethyl chromatography. Western Blot was used to qualitatively analyse the fragments. Results Versikine plasma concentration was higher in TAA patients compared to controls (34.23±3.83 vs 10.05±1.15 ng/mL, p<0.0001). In TAA patients, versikine concentration was negatively correlated with the aortic diameter (r=-0.3712, p=0.0218) and outer curve thickness (r=-0.3819, p=0.0493). ADAMTS4 plasma concentration was lower in TAA patients compared to controls (11.02±2.88 vs 25.02±5.07 ng/mL, p=0.0114). ADAMTS5, ADAMTS13 and vWF concentrations were similar in both groups. Versikine plasma levels could identify TAA with a sensitivity of 68.1% and specificity of 95.6%. In addition, high levels of versikine were present in the aneurysmal aortic tissue. • Download figure • Open in new tab • Download powerpoint Abstract BS57 Figure 1 Schematic Representation of Thoracic Aortic Aneurysm (TAA) pathogenesis and biomarker panel selection. A) A diagram of the thoracic aneurysm in the ascending aorta where the tunica media layer of the aorta has been zoomed in to show an accumulation of proteoglycans (PG) in the extracellular matrix (ECM) where the smooth muscle cells (SMCs) reside. The wider lumen can be seen in TAA aorta compared to healthy aorta. There is also loss of SMCs in the media layer. B) Normal aorta in healthy adult where a reduced content of proteoglycans (PGs) can be observed compared to A. C) Blood sample taken from patients and healthy controls. D) 96-Well Plate used for all the Enzyme-linked immunosorbent assay (ELISA) experiments run in the lab to measure plasma content of the potential biomarkers. E) The list of the different molecules that were measured to include in the biomarker panel and to analyse their levels compared to the aortic properties in TAA patients.PG=proteoglycan, SMCs=smooth muscle cells, ECM=extracellular matrix, ADAMTS= A Disintegrin and Metalloproteinase with Thrombospondin Motif, vWF= von Willebrand Factor. • Download figure • Open in new tab • Download powerpoint Abstract BS57 Figure 2 Proteoglycan extraction in human aortic tissue. 1) Aortic aneurysm tissue sample obtained straight after aortic aneurysm repair surgery from the ascending aorta. 2) Adventitia was removed due to the thrombi and fatty deposits that make dissection into smaller fragments challenging. We were interested in extracting proteoglycans mainly from the aortic media layer. 3) After tissue was dissected into superior (region further away from the aortic valve) and inferior (region of the tissue closer to the aortic valve), the tissue was further dissected into square 1.5x1.5cm fragments and stored in -80 after freezing with liquid nitrogen. 4) Frozen tissue was homogenized using a mortar and pestle until it looked almost like a powder. 5) 10mL 4M Guanidine Extraction buffer was adder per 1 g of tissue and homogenate was further centrifugated at speed 18000g for 45 minutes. 6) The filtered homogenate was loaded onto the fast protein liquid chromatography (FPLC) using Diethylaminoethyl cellulose (DEAE). Absorbance was read at OD280 and high OD corresponded to fractions 4-6 and 11-19. 2 mL fractions were collected including the starting material (SM), flowthrough (FT), washing (W). 7) 20uL of all the fractions including SM, W, FT were stained with Dimethylmethylene Blue Assay (DMMB) which binds to glycosaminoglycans (GAGs) and showed high GAG content in fractions 15-17, the SM,FT and W. 8) Western blot analysis using anti-Chondroitin Sulphate (CS) primary antibody showed high protein content with molecular weight 250 kilodalton(kDa) in the SM, FT,W and fractions 15-17. Protein with molecular weight 37kDa was present in SM, FT,W and fractions 14-18. Fractions 15-17 were pooled into pool 1 and fractions 14 and 18 were pooled in pool 2 and underwent another western blot analysis using anti-DPEAAE. The neoepitope antibody detects an N-terminal versican fragment generated by ADAMTS5 cleavage at Glu441 -Ala442 bond (versikine). 10 uL of Pool 2 showed presence of versikine. Anti-G1, anti-full length versican and anti-biglycan antibodies did not give any results using 10mL of the pooled fractions. Conclusion Versikine levels are higher in the plasma of TAA patients which may be due to the high turnover of versican in the aortic tissue. Versikine levels correlated with both aortic diameter and outer curve aortic thickness. Lower ADAMTS4 levels suggest reduced proteolysis which may contribute to the accumulation of proteoglycans in the tissue. Versikine has potential to become a reliable biomarker for diagnosing a TAA. Larger trials including CTD and bicuspid valve patients are required to validate versikine as a biomarker and test its’ ability to predict aortic diameter changes over time. Conflict of Interest none

Background The decision to conserve or replace the native aortic valve following acute type‐A aortic dissection (ATAAD) is an area of cardiac surgery without standardized practice. This single‐center retrospective study analysed the long‐term performance of the native aortic valve and root following surgery for ATAAD. Methods Between 2009 and 2018 all cases ATAAD treated at Royal Brompton and Harefield NHS Foundation Trust were analysed. Patients were divided into two groups: (a) ascending aorta (interposition) graft (AAG) without valve replacement and (b) nonvalve‐sparing aortic root replacement (ARR). Preoperative covariates were compared, as well as operative characteristics and postoperative complications. Long‐term survival and echocardiographic outcomes were analysed using regression analysis. Results In total, 116 patients were included: 63 patients in the AAG group and 53 patients in the ARR group. In patients where the native aortic valve was conserved, nine developed severe aortic regurgitation and two patients developed dilation of the aortic root requiring subsequent replacement during the follow‐up period. Aortic regurgitation at presentation was not found to be associated with subsequent risk of developing severe aortic regurgitation or reintervention on the aortic valve. Overall mortality was observed to be significantly lower in patients undergoing AAG (17.5% vs. 41.5%, p = .004). Conclusions With careful patient selection, the native aortic root shows good long‐term durability both in terms of valve competence and stable root dimensions after surgery for ATAAD. This study supports the consideration of conservation of the aortic valve during emergency surgery for type‐A dissection, in the absence of a definitive indication for root replacement, including in cases where aortic regurgitation complicates the presentation.