Sutureless Biological Aortic Valve Replacement (Su-AVR) in Redo operations: a retrospective real-world experience report of clinical and echocardiographic outcomes.

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.

Comparison of outcomes between aortic root replacement and supra-coronary interposition graft for type A aortic dissection: A retrospective case series.

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.

Rapid deployment technology versus conventional sutured bioprostheses in aortic valve replacement.

OBJECTIVES: Despite the benefits of rapid deployment aortic valve prostheses (RDAVR), conventional sutured valves (cAVR) are more commonly used in the treatment for aortic stenosis. Given the paucity of randomized studies, this study aimed to synthesize available data to compare both treatment options. METHODS: A systematic search of Pubmed, OVID, and MEDLINE was conducted to retrieve comparative studies for RDAVR versus cAVR in the treatment of aortic stenosis. Out of 1773 returned titles, 35 papers were used in the final analysis, including 1 randomized study, 1 registry study, 6 propensity-matched studies, and 28 observational studies, incorporating a total of 10,381 participants (RDAVR n = 3686; cAVR n = 6310). RESULTS: Random-effects meta-analysis found no difference between the two treatment groups in terms of operative mortality, stroke, or bleeding (p > .05). The RDAVR group had reduced cardiopulmonary bypass (standardized mean difference [SMD]: -1.28, 95% confidence interval [CI]: [-1.35, -1.20], p < .001) and cross-clamp times (SMD: -1.05, 95% CI: [-1.12, -0.98], p < .001). Length of stay in the intensive care unit was also shorter in the RDAVR group (SMD: -0.385, 95% CI: [-0.679, -0.092], p = .010). The risk of pacemaker insertion was higher for RDAVR (odds ratio [OR]: 2.41, 95% CI: [1.92, 3.01], p < .001) as was the risk of paravalvular leak (PVL) at midterm follow-up (OR: 2.52, 95% CI: [1.32, 4.79], p = .005). Effective orifice area and transvalvular gradient were more favorable in RDAVR patients (p > .05). CONCLUSIONS: Despite the benefits of RDAVR in terms of reduced operative time and enhanced recovery, the risk of pacemaker insertion and midterm PVL remains a significant cause for concern.

The impact of COVID-19 pandemic on aortic valve surgical service: a single centre experience.

BACKGROUND: The coronavirus-disease 2019 (COVID-19) pandemic imposed an unprecedented burden on the provision of cardiac surgical services. The reallocation of workforce and resources necessitated the postponement of elective operations in this cohort of high-risk patients. We investigated the impact of this outbreak on the aortic valve surgery activity at a single two-site centre in the United Kingdom. METHODS: Data were extracted from the local surgical database, including the demographics, clinical characteristics, and outcomes of patients operated on from March 2020 to May 2020 with only one of the two sites resuming operative activity and compared with the respective 2019 period. A similar comparison was conducted with the period between June 2020 and August 2020, when operative activity was restored at both institutional sites. The experience of centres world-wide was invoked to assess the efficiency of our services. RESULTS: There was an initial 38.2% reduction in the total number of operations with a 70% reduction in elective cases, compared with a 159% increase in urgent and emergency operations. The attendant surgical risk was significantly higher [median Euroscore II was 2.7 [1.9-5.2] in 2020 versus 2.1 [0.9-3.7] in 2019 (p = 0.005)] but neither 30-day survival nor freedom from major post-operative complications (re-sternotomy for bleeding/tamponade, transient ischemic attack/stroke, renal replacement therapy) was compromised (p > 0.05 for all comparisons). Recommencement of activity at both institutional sites conferred a surgical volume within 17% of the pre-COVID-19 era. CONCLUSIONS: Our institution managed to offer a considerable volume of aortic valve surgical activity over the first COVID-19 outbreak to a cohort of higher-risk patients, without compromising post-operative outcomes. A backlog of elective cases is expected to develop, the accommodation of which after surgical activity normalisation will be crucial to monitor.

Preoperative C-reactive protein as a predictor of postoperative acute kidney injury in patients undergoing coronary artery bypass grafting.

C-reactive protein is a well-known marker of inflammation and may be preoperatively elevated in the absence of infection in adult cardiac surgery patients, indicating a baseline inflammatory process. We conducted a literature search to assess the available evidence on whether there is an association between preoperative C-reactive protein and acute kidney injury after coronary artery bypass grafting. Included only were observational studies which investigated this association. We excluded abstracts, case reports, animal studies and articles in languages other than English. Altogether, 199 papers were retrieved from the search strategy reported, of which 6 studies were included in the final review. The study types, publication details, patient groups and key results are tabulated. A qualitative assessment of these papers was conducted. We conclude that there is some evidence to support the association between high preoperative C-reactive protein level and postoperative acute kidney injury and complications after coronary artery bypass grafting. Owing to variability in acute kidney injury definitions and C-reactive protein levels for different cohorts in the observational studies reviewed, it is unclear from current evidence what serum C-reactive protein cut-off level is significantly associated with postoperative acute kidney injury. Further evidence is needed to investigate whether raised preoperative C-reactive protein in the absence of an infective cause could have a role in risk prediction models for cardiac surgery-associated acute kidney injury.

Establishing the Safety of Training in Off-Pump Coronary Artery Bypass Surgery: A Retrospective Comparison of Outcomes between Trainees and a Consultant Surgeon.

BACKGROUND: The safety of training in off-pump coronary artery bypass (OPCAB) surgery and the stage at which trainees should be exposed to this technique remain controversial. This single-center retrospective study aimed to compare outcomes of OPCAB surgery in consultant and trainee cases. METHODS: Between 2014 and 2018, all isolated OPCAB operations performed under the care of a consultant surgeon (G.A.) were analyzed. Cases where a surgeon below consultant grade performed at least 70% of the distal anastomoses were designated as "trainee cases" with the remaining cases designated as "consultant cases." The baseline characteristics of patients, perioperative data, and short-term outcomes were prospectively collated and analyzed. RESULTS: During the study period, 245 OPCAB cases were identified: 142 (58%) consultant and 103 (42%) trainee cases. The trainee cases were performed exclusively by trainees in the final 2 years of the UK National Cardiothoracic Training Program. Both trainee and consultant groups had low mortality with two perioperative deaths occurring in either group. The rates of serious postoperative complications including stroke (n = 1 vs. 2, p = 0.759), resternotomy for bleeding (n = 3 vs. 7, p = 0.431), and mediastinal infection (n = 2 vs. 3, p = 0.926) were low and not significantly different between the two groups. Patients operated on by trainees had a slightly longer hospital stay than those operated on by the consultant surgeon, although this did not reach statistical significance (9.9 vs. 7.9 days). CONCLUSIONS: These results demonstrate comparable outcomes in OPCAB surgery between a consultant surgeon and trainees. This study supports the conclusion that training surgeons in OPCAB is appropriate for trainees in the final years of cardiac surgery training.

Aortic root replacement to treat type A aortic dissection: A comparison of midterm outcomes between composite valve grafts and porcine aortic roots.

BACKGROUND: Porcine aortic roots (PAR) have been reported in the literature with acceptable short- and long-term outcomes for the treatment of aortic root aneurysms. However, their efficacy in type A aortic dissection (TAAD) is yet to be defined. METHODS: Using data from a locally collated aortic dissection registry, we compared the outcomes in patients undergoing aortic root replacement for TAAD using either of two surgical options: (a) PAR or (b) composite valve grafts (CVG). A retrospective analysis was conducted for all procedures in the period from 2005 to 2018. RESULTS: A total of 252 patients underwent procedures for TAAD in the time period. Sixty-five patients had aortic root replacements (PAR n = 30, CVG n = 35). Between-group comparisons identified a younger CVG group (50.5 vs 64.5, P < .05) although all other covariates were comparable. Operative parameters were comparable between the two groups. The use of PAR did not significantly impact operative mortality (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.22-3.61; P = .992), stroke (OR, 2.91, 0.25-34.09, P = .395), reoperation (OR, 0.91; 95% CI, 0.22-3.62; P = .882) or length of stay (coeff 2.33, -8.23 to 12.90; P = .659) compared to CVG. Five-year survival was similar between both groups (PAR 59% vs CVG 69%; P = .153) and reoperation was negligible. Echocardiography revealed significantly lower aortic valve gradients in the PAR group (8.69 vs 15.45mm Hg; P < .0001), and smaller left ventricular dimensions both at 6-week and 1-year follow-up (P < .05). CONCLUSIONS: This study highlights the comparable short- and midterm outcomes of PAR in cases of TAAD, in comparison to established therapy.

Identification of myocardial diffuse fibrosis by 11 heartbeat MOLLI T 1 mapping: averaging to improve precision and correlation with collagen volume fraction.

OBJECTIVES: Our objectives involved identifying whether repeated averaging in basal and mid left ventricular myocardial levels improves precision and correlation with collagen volume fraction for 11 heartbeat MOLLI T 1 mapping versus assessment at a single ventricular level. MATERIALS AND METHODS: For assessment of T 1 mapping precision, a cohort of 15 healthy volunteers underwent two CMR scans on separate days using an 11 heartbeat MOLLI with a 5(3)3 beat scheme to measure native T 1 and a 4(1)3(1)2 beat post-contrast scheme to measure post-contrast T 1, allowing calculation of partition coefficient and ECV. To assess correlation of T 1 mapping with collagen volume fraction, a separate cohort of ten aortic stenosis patients scheduled to undergo surgery underwent one CMR scan with this 11 heartbeat MOLLI scheme, followed by intraoperative tru-cut myocardial biopsy. Six models of myocardial diffuse fibrosis assessment were established with incremental inclusion of imaging by averaging of the basal and mid-myocardial left ventricular levels, and each model was assessed for precision and correlation with collagen volume fraction. RESULTS: A model using 11 heart beat MOLLI imaging of two basal and two mid ventricular level averaged T 1 maps provided improved precision (Intraclass correlation 0.93 vs 0.84) and correlation with histology (R 2 = 0.83 vs 0.36) for diffuse fibrosis compared to a single mid-ventricular level alone. ECV was more precise and correlated better than native T 1 mapping. CONCLUSION: T 1 mapping sequences with repeated averaging could be considered for applications of 11 heartbeat MOLLI, especially when small changes in native T 1/ECV might affect clinical management.

Comparison of early and late quality of life between left anterior thoracotomy and median sternotomy off-pump coronary artery bypass surgery.

OBJECTIVE: Minimally invasive coronary artery bypass surgery performed through a left thoracotomy has potential benefits over conventional sternotomy, including reduced surgical trauma, faster recovery and potential improvement in quality of life. This study is a prospective assessment of quality of life in patients undergoing off-pump coronary bypass by median sternotomy and left anterior thoracotomy. METHODS: Quality of life was assessed by the EuroQoL questionnaire, with additional questions on dyspnoea, angina, wound pain and scar aesthetics. Outcomes were compared across the data sets at pre-operation, three weeks and three months post-operation. RESULTS: Sixty-six (17 minimally invasive and 49 off-pump) patients (mean age 65±12, 7 females and 59 males) were included. Significant differences in mean EuroQol outcomes were observed for activities, F(1,64) = 5.86, (p<0.05), pain scores, F(1,64) = 4.658 (p=0.035) and scar aesthetics, F(1,64) = 16.83 (p<0.05). There was an additional significant interaction, F(1.898, 121.49) = 3.282, (p<0.05), between time and group for activity levels; exploring this further indicated no significant difference at baseline, but significantly greater improvement observed in the minimally invasive group over time. At 3 weeks, 50% of minimally invasive patients compared to 82% of sternotomy patients (p<0.001) required oral analgesia. At 3 months, 8% of minimally invasive patients and 21% of sternotomy patients (p<0.001) required oral analgesia. CONCLUSIONS: Off-pump coronary artery bypass performed with a minimally invasive approach through a left thoracotomy appears to result in earlier improvement in quality of life outcomes compared to conventional sternotomy. These results are important when counselling patients regarding the benefits and difference between a left anterior thoractomy MIDCABG and conventional OPCAB and can be used as pilot data for a larger trial examining differences in the MIDCABG and conventional full sternotomy OPCAB procedures.

Impact of hepatic cirrhosis on outcome in adult cardiac surgery.

Increasing prevalence of hepatic disease is likely to translate in a growing number of patients with significant hepatic disease requiring cardiac surgery. Available cardiac risk stratification models do not address the risk associated with hepatic disease. However, weighted mean mortality rates based on previous studies of cardiac surgery in patients with hepatic disease demonstrate operative mortality rates that range from 9.88% (standard deviation [SD] 9.69) for patients in Child-Turcotte-Pugh (CTP) class A cirrhosis to 69.23% (SD 28.55) for patients with CTP class C cirrhosis. This review comprehensively appraises the pathophysiology of hepatic disease, reported clinical outcomes and considerations for risk stratification.

Perceval sutureless bioprosthesis versus Perimount sutured bioprosthesis for aortic valve replacement in patients with aortic stenosis: a retrospective, propensity-matched study.

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.

Thrombocytopenia after sutureless and standard stented aortic valve replacement: a retrospective analysis of risk factors, clinical course, and early outcome.

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.

Petechial Rash and Glomerulonephritis: First Presentation of Endocarditis on a Patent Foramen Ovale Closure Device.

Patent foramen ovale device closure is rarely associated with complications. This case report is believed to be the first description of a patient with infective endocarditis of a patent foramen ovale closure device presenting as glomerulonephritis. This article serves to educate as to this rare device complication and its unusual presentation. (Level of Difficulty: Intermediate.).

Symptom attribution is a stronger predictor of PVT-failure than symptom endorsement in treatment-seeking Veterans with remote mTBI history: A pilot study.

OBJECTIVE: To examine relationships between performance validity testing (PVT), neurobehavioral symptom endorsement, and symptom attribution in Veterans with a history of mild traumatic brain injury (mTBI). METHOD: Participants included treatment-seeking Veterans (n = 37) with remote mTBI histories who underwent a neuropsychological assessment and completed a modified version of the Neurobehavioral Symptom Inventory (NSI) to assess symptom endorsement and symptom attribution (the latter evaluated by having Veterans indicate whether they believed each NSI symptom was caused by their mTBI). Veterans were divided into two subgroups, PVT-Valid (n = 25) and PVT-Invalid (n = 12). RESULTS: Independent samples t-tests showed that two of five symptom endorsement variables and all five symptom attribution variables were significantly different between PVT groups (PVT-Invalid > PVT-Valid; Cohen's d = 0.67-1.02). Logistic regression analyses adjusting for PTSD symptoms showed that symptom endorsement (Nagelkerke's R2 = .233) and symptom attribution (Nagelkerke's R2 = .279) significantly distinguished between PVT groups. According to the Wald criterion, greater symptom endorsement (OR = 1.09) and higher attribution of symptoms to mTBI (OR = 1.21) each reliably predicted PVT-failure. CONCLUSIONS: While both symptom endorsement and symptom attribution were significantly associated with PVT-failure, our preliminary results suggest that symptom attribution is a stronger predictor of PVT-failure. Results highlight the importance of assessing symptom attribution to mTBI in this population.

Time to TAVI: streamlining the pathway to treatment.

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.

Management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis.

OBJECTIVES: The management of severe aortic stenosis mandates consideration of aortic valve intervention for symptomatic patients. However, for asymptomatic patients with severe aortic stenosis, recent randomised trials supported earlier intervention. We conducted a systematic review and meta-analysis to evaluate all the available data comparing the two management strategies. METHODS: PubMed, Cochrane and Web of Science databases were systematically searched from inception until 10 January 2022. The search key terms were 'asymptomatic', 'severe aortic stenosis' and 'intervention'. RESULTS: Meta-analysis of two published randomised trials, AVATAR and RECOVERY, included 302 patients and showed that early intervention resulted in 55% reduction in all-cause mortality (HR=0.45, 95% CI 0.24 to 0.86; I2 0%) and 79% reduction in risk of hospitalisation for heart failure (HR=0.21, 95% CI 0.05 to 0.96; I2 15%). There was no difference in risk of cardiovascular death between the two groups (HR=0.36, 95% CI 0.03 to 3.78; I2 78%). Additionally, meta-analysis of eight observational studies showed improved mortality in patients treated with early intervention (HR=0.38, 95% CI 0.26 to 0.56; I2 77%). CONCLUSION: This meta-analysis provides evidence that, in patients with severe asymptomatic aortic stenosis, early intervention reduces all-cause mortality and improves outcomes compared with conservative management. While this is very encouraging, further randomised controlled studies are needed to draw firm conclusions and identify the optimal timing of intervention. PROSPERO REGISTRATION NUMBER: CRD42022301037.

Determining the genetic contribution in patients with non-syndromic ascending thoracic aortic aneurysms: Correlation with findings from computational pathology.

OBJECTIVES: This study aims to identify the clinical utility of targeted-genetic sequencing in a cohort of patients with TAA and establish a new method for regional histological characterisation of TAA disease. METHODS: Fifty-four patients undergoing surgery for proximal TAA were recruited. EXCLUSIONS: connective tissue disease, bicuspid aortic valves, redo surgery. All patients underwent next generation sequencing (NGS) using a custom gene panel containing 63 genes previously associated with TAA on Illumina MiSeqor NextSeq550 platforms. Explanted TAA tissue was obtained en-bloc from 34/54 patients, and complete circumferential strips of TAA tissue processed into whole slides which were subsequently digitalised. Computational pathology methods were employed to quantify elastin, cellularity and collagen in six equally divided regions across the whole aneurysm circumference. RESULTS: Of 54 patients, clearly pathogenic or potentially pathogenic variants were found in 7.4%: namely LOX, PRKG1, TGFBR1 and SMAD3 genes. 55% had at least one variant of unknown significance (VUS) and seven of the VUSs were in genes with a strong disease association (category A) genes, whilst 15 were from moderate risk (category B) genes. Elastin and collagen abundance displayed high regional variation throughout the aneurysm circumference. In patients with <60% total elastin, the loss of elastin was more significant on the outer curve (38.0% vs 47.4%, p = 0.0094). The presence of VUS, higher pulse wave velocity and advancing age were predictors of elastin loss (regression analysis: p < 0.05). CONCLUSIONS: These findings demonstrate the heterogeneity of TAA disease microstructure and the potential link between histological appearance and clinical factors, including genetic variation.

Effectiveness of maternal vaccination with quadrivalent inactivated influenza vaccine in pregnant women and their infants in 2019-2020.

OBJECTIVES: Influenza is associated with an increased risk for serious illness, hospitalization, and death in pregnant women and young infants. Our aim was to estimate the effectiveness of a quadrivalent inactivated influenza vaccine (QIV) in pregnant women and their infants during 2019-2020. METHODS: A QIV vaccine was offered to pregnant women followed in a maternity hospital. Women were contacted weekly during the influenza season and asked about symptoms. Polymerase chain reaction testing in pharyngeal samples was offered to pregnant women and infants with influenza-like illness. A Bayesian beta-binomial model was used. RESULTS: We studied 636 pregnant women (406 vaccinated and 230 unvaccinated) and 474 infants (281 of mothers vaccinated in pregnancy and 193 of unvaccinated mothers). Using a Bayesian beta-binomial model, it was estimated that influenza vaccination of pregnant women reduced their logit to develop laboratory-confirmed influenza by -4.2 (95% CI -3,7 - 4,7) and the logit of their infants to develop laboratory-confirmed influenza by -4.2 (95% CI -3.6, -4.9). The QIV effectiveness against laboratory-confirmed influenza was 43.5% in pregnant women and 31.4% in infants. CONCLUSION: Maternal influenza vaccination with QIV in pregnancy reduced the odds of pregnant women and their infants to develop influenza. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT04723771.

Association of hemodynamic factors and progressive aortic dilatation following type A aortic dissection surgical repair.

Type A aortic dissection (TAAD) involves the ascending aorta or the arch. Acute TAAD usually requires urgent replacement of the ascending aorta. However, a subset of these patients develops aortic rupture due to further dilatation of the residual dissected aorta. There is currently no reliable means to predict the risk of dilatation following TAAD repair. In this study, we performed a comprehensive morphological and hemodynamic analysis for patients with and without progressive aortic dilatation following surgical replacement of the ascending aorta. Patient-specific models of repaired TAAD were reconstructed from post-surgery computed tomography images for detailed computational fluid dynamic analysis. Geometric and hemodynamic parameters were evaluated and compared between patients with stable aortic diameters (N = 9) and those with aortic dilatation (N = 8). Our results showed that the number of re-entry tears and true/false lumen pressure difference were significantly different between the two groups. Patients with progressive aortic dilatation had higher luminal pressure difference (6.7 [4.6, 10.9] vs. 0.9 [0.5, 2.3] mmHg; P = 0.001) and fewer re-entry tears (1.5 [1, 2.8] vs. 5 [3.3, 7.5]; P = 0.02) compared to patients with stable aortic diameters, suggesting that these factors may serve as potential predictors of aneurysmal dilatation following surgical repair of TAAD.