Sex-related differences among patients undergoing surgical aortic valve replacement-a propensity score matched study.

OBJECTIVES: We investigated the sex-related difference in characteristics and 2-year outcomes after surgical aortic valve replacement (SAVR) by propensity-score matching (PSM). METHODS: Data from 2 prospective registries, the INSPIRIS RESILIA Durability Registry (INDURE) and IMPACT, were merged, resulting in a total of 933 patients: 735 males and 253 females undergoing first-time SAVR. The PSM was performed to assess the impact of sex on the SAVR outcomes, yielding 433 males and 243 females with comparable baseline characteristics. RESULTS: Females had a lower body mass index (median 27.1 vs 28.0 kg/m2; P = 0.008), fewer bicuspid valves (52% vs 59%; P = 0.036), higher EuroSCORE II (mean 2.3 vs 1.8%; P < 0.001) and Society of Thoracic Surgeons score (mean 1.6 vs 0.9%; P < 0.001), were more often in New York Heart Association functional class III/IV (47% vs 30%; P < 0.001) and angina Canadian Cardiovascular Society III/IV (8.2% vs 4.4%; P < 0.001), but had a lower rate of myocardial infarction (1.9% vs 5.2%; P = 0.028) compared to males. These differences vanished after PSM, except for the EuroSCORE II and Society of Thoracic Surgeons scores, which were still significantly higher in females. Furthermore, females required smaller valves (median diameter 23.0 vs 25.0 mm, P < 0.001). There were no differences in the length of hospital stay (median 8 days) or intensive care unit stay (median 24 vs 25 hours) between the 2 sexes. At 2 years, post-SAVR outcomes were comparable between males and females, even after PSM. CONCLUSIONS: Despite females presenting with a significantly higher surgical risk profile, 2-year outcomes following SAVR were comparable between males and females.

Outcomes of Surgical Ablation for Atrial Fibrillation in On- versus Off-pump Coronary Artery Bypass Grafting.

OBJECTIVES: A considerable number of patients undergoing coronary artery bypass grafting surgery suffer from atrial fibrillation and should be treated concomitantly. This manuscript evaluates the impact of on-pump versus off-pump bypass grafting on the applied lesion-set and rhythm outcome. METHODS: Between January 2017 and April 2020 patients who underwent combined bypass grafting and surgical ablation for atrial fibrillation were consecutively enrolled in the German CArdioSurgEry Atrial Fibrillation registry (CASE-AF, 17 centers). Data were prospectively collected. Follow-up was planned after one year. RESULTS: 224 Patients were enrolled. No differences in baseline characteristics were seen between on- and off-pump bypass grafting, especially not in type of atrial fibrillation and left atrial size. In the on-pump group (n = 171, 76%), pulmonary vein isolation and an extended left atrial lesion-set were performed more often compared to off-pump bypass grafting. (58% vs 26%, 33 vs 9%, respectively, p < 0.001). In off-pump bypass grafting a box isolating the atrial posterior wall was the dominant lesion (72% off-pump vs 42% on-pump, p < 0.001). Left-atrial appendage management was comparable in on-pump vs off-pump bypass grafting (94% vs 91%, p = 0.37). Sinus rhythm at follow-up was confirmed in 61% in the on-pump group and in 65% in the off-pump group (p = 0.66). No differences were seen in in-hospital or follow-up complication-rates between the two groups. CONCLUSIONS: In coronary artery bypass grafting patients undergoing concomitant atrial fibrillation ablation, our data suggests that the technique applied for myocardial revascularization (off-pump vs on-pump) leads to differences in the ablation lesion set, but not in safety and effectiveness.

Minimally invasive extracorporeal circulation versus conventional cardiopulmonary bypass in patients undergoing cardiac surgery (MiECS): Rationale and design of a multicentre randomised trial.

INTRODUCTION: The ultimate answer to the question whether minimal invasive extracorporeal circulation (MiECC) represents the optimal perfusion technique in contemporary clinical practice remains elusive. The present study is a real-world study that focuses on specific perfusion-related clinical outcomes after cardiac surgery that could potentially be favourably affected by MiECC and thereby influence the future clinical practice. METHODS: The MiECS study is an international, multi-centre, two-arm randomized controlled trial. Patients undergoing elective or urgent coronary artery bypass grafting (CABG), aortic valve replacement (AVR) or combined procedure (CABG + AVR) using extracorporeal circulation will be randomized to MiECC or contemporary conventional cardiopulmonary bypass (cCPB). Use of optimized conventional circuits as controls is acceptable. The study design includes a range of features to prevent bias and is registered at clinicaltrials.gov (NCT05487612). RESULTS: The primary outcome is a composite of postoperative serious adverse events that could be related to perfusion technique occurring up to 30 days postoperatively. Secondary outcomes include use of blood products, ICU and hospital length of stay (30 days) as well as health-related quality of life (30 and 90 days). CONCLUSIONS: The MiECS trial has been designed to overcome perceived limitation of previous trials of MiECC. Results of the proposed study could affect current perfusion practice towards advancement of patient care.

Feasibility of aligning creatine kinase MB activity and mass data in multicentre trials using generalized additive modelling.

OBJECTIVES: Elevated serum creatine kinase isoenzyme MB (CK-MB) levels indicate myocardial ischaemia and periprocedural myocardial injury during treatment of heart diseases. We established a method to predict CK-MB mass from activity data based on a prospective pilot study in order to simplify multicentre trials. METHODS: 38 elective cardiac surgery patients without acute myocardial ischaemia and terminal renal failure were recruited. CK-MB mass and activity were determined in venous blood samples drawn preoperatively, postoperatively, 6 h post-op, and 12 h post-op. Linear regression and generalized additive models (GAMs) were applied to describe the relationship of mass and activity. Influences of demographic and perioperative factors on the fit of GAMs was evaluated. The agreement of predicted and measured CK-MB masses was assessed by Bland-Altman analyses. RESULTS: Linear regression provided an acceptable overall fit (r2 = 0.834) but showed deviances at low CK-MB levels. GAMs did not benefit from the inclusion of age, body mass index and surgical times. The minimal adequate model predicted CK-MB masses from activities, sex and sampling time with an r2 of 0.981. Bland-Altman analyses confirmed narrow limits of agreement (spread: 8.87 µg/l) and the absence of fixed (P = 0.41) and proportional (P = 0.21) biases. CONCLUSIONS: GAM-based modelling of CK-MB data in a representative patient cohort allowed to predict CK-MB masses from activities, sex and sampling time. This approach simplifies the integration of study centres with incompatible CK-MB data into multicentre trials in order to facilitate inclusion of CK-MB levels in statistical models.

Conventional versus minimally invasive extra-corporeal circulation in patients undergoing cardiac surgery: A randomized controlled trial (COMICS).

INTRODUCTION: The trial hypothesized that minimally invasive extra-corporeal circulation (MiECC) reduces the risk of serious adverse events (SAEs) after cardiac surgery operations requiring extra-corporeal circulation without circulatory arrest. METHODS: This is a multicentre, international randomized controlled trial across fourteen cardiac surgery centres including patients aged ≥18 and <85 years undergoing elective or urgent isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR) surgery, or CABG + AVR surgery. Participants were randomized to MiECC or conventional extra-corporeal circulation (CECC), stratified by centre and operation. The primary outcome was a composite of 12 post-operative SAEs up to 30 days after surgery, the risk of which MiECC was hypothesized to reduce. Secondary outcomes comprised: other SAEs; all-cause mortality; transfusion of blood products; time to discharge from intensive care and hospital; health-related quality-of-life. Analyses were performed on a modified intention-to-treat basis. RESULTS: The trial terminated early due to the COVID-19 pandemic; 1071 participants (896 isolated CABG, 97 isolated AVR, 69 CABG + AVR) with median age 66 years and median EuroSCORE II 1.24 were randomized (535 to MiECC, 536 to CECC). Twenty-six participants withdrew after randomization, 22 before and four after intervention. Fifty of 517 (9.7%) randomized to MiECC and 69/522 (13.2%) randomized to CECC group experienced the primary outcome (risk ratio = 0.732, 95% confidence interval (95% CI) = 0.556 to 0.962, p = 0.025). The risk of any SAE not contributing to the primary outcome was similarly reduced (risk ratio = 0.791, 95% CI 0.530 to 1.179, p = 0.250). CONCLUSIONS: MiECC reduces the relative risk of primary outcome events by about 25%. The risk of other SAEs was similarly reduced. Because the trial terminated early without achieving the target sample size, these potential benefits of MiECC are uncertain.

Epicardial and endocardial surgical ablation of atrial fibrillation: outcomes from CASE-AF Registry.

OBJECTIVES: The German CArdioSurgEry Atrial Fibrillation Registry is a prospective, multicentric registry analysing outcomes of patients undergoing surgical ablation for atrial fibrillation as concomitant or stand-alone procedures. This data sub-analysis of the German CArdioSurgEry Atrial Fibrillation Registry aims to describe the in-hospital and 1-year outcomes after concomitant surgical ablation, based on 2 different ablation approaches, epicardial and endocardial surgical ablation. METHODS: Between January 2017 and April 2020, 17 German cardiosurgical units enrolled 763 consecutive patients after concomitant surgical ablation. In the epicardial group, 413 patients (54.1%), 95.6% underwent radiofrequency ablation. In the endocardial group, 350 patients (45.9%), 97.7% underwent cryoablation. 61.5% of patients in the epicardial group and 49.4% of patients in the endocardial group presenting with paroxysmal atrial fibrillation. Pre-, intra- and post-operative data were gathered. RESULTS: Upon discharge, 32.3% (n = 109) of patients after epicardial surgical ablation and 24.0% (n = 72) of patients after endocardial surgical ablation showed recurrence of atrial fibrillation. The in-hospital mortality rate was low, 2.2% (n = 9) in the epicardial and 2.9% (n = 10) in the endocardial group. The overall 1-year procedural success rate was 58.4% in the epicardial and 62.2% in the endocardial group, with significant symptom improvement in both groups. The 1-year mortality rate was 7.7% (n = 30) in epicardial and 5.0% (n = 17) in the endocardial group. CONCLUSIONS: Concomitant surgical ablation is safe and effective with significant improvement in patient symptoms and freedom from atrial fibrillation. Adequate cardiac rhythm monitoring should be prioritized for higher quality data acquisition.

Impact of aortic root geometry and degree of aortic calcification on outcomes of patients undergoing TAVI procedure.

AIMS: Adequate differentiation of calcifications in contrast-enhanced CT scans remains difficult to assess TAVI parameters. The size of the aortic leaflets has not been taken into account so far in present studies. The aim of our study was to establish a new method for optimized quantification of the aortic valve calcification degree in contrast-enhanced CT scans for better preoperative prediction of postoperative paravalvular leak after TAVI. METHODS AND RESULTS: We retrospectively analyzed preoperative contrast-enhanced CT scans of patients who underwent TAVI in our institution between 2014 and 2017. Calcium volume was quantified by a method using contrast enhanced computer tomography (3mensio-Structural Heart-7.2 software) with different iodine contents for better discrimination of contrast agent from calcium and by an individually set Houndsfield Unit (HU) threshold with 50HU above the individually determined reference value. Calcium volume was correlated with surface area of each aortic cusp. Perioperative variables were analyzed. All patients (n = 150) with severe aortic stenosis were treated with TAVI implantation. Overall incidence of postoperative trace to moderate PVL was 37%. The amount of calcium correlated with the incidence of PVL. In a logistic regression analysis total volume of calcification (p = .032) as well as calcification of each aortic cusp (NC_p = .001; RC_p < .001; LC_p = .001) were independent predictors. CONCLUSIONS: Calcification degree as well as its correlation with the surface area of each aortic cusp significantly influence incidence of PVL. Our new method improves preoperative quantification of the calcification degree by use of contrast agents with different iodine contents and thereby helps to improve patients' outcomes.

Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells.

The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors of increasing age, and discovered the heterogeneous mSV landscapes of hematopoietic stem and progenitor cells. While mSVs are continuously acquired throughout life, expanded subclones in our cohort are confined to individuals >60. Cells already harboring mSVs are more likely to acquire additional somatic structural variants, including megabase-scale segmental aneuploidies. Capitalizing on comprehensive single-cell micrococcal nuclease digestion with sequencing reference data, we conducted high-resolution cell-typing for eight hematopoietic stem and progenitor cells. Clonally expanded mSVs disrupt normal cellular function by dysregulating diverse cellular pathways, and enriching for myeloid progenitors. Our findings underscore the contribution of mSVs to the cellular and molecular phenotypes associated with the aging hematopoietic system, and establish a foundation for deciphering the molecular links between mSVs, aging and disease susceptibility in normal tissues.

Intraoperative haemoadsorption for antithrombotic drug removal during cardiac surgery: initial report of the international safe and timely antithrombotic removal (STAR) registry.

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period.Clinical registration number: ClinicalTrials.gov identifier: NCT05077124.

Segmentation-based cardiomegaly detection based on semi-supervised estimation of cardiothoracic ratio.

The successful integration of neural networks in a clinical setting is still uncommon despite major successes achieved by artificial intelligence in other domains. This is mainly due to the black box characteristic of most optimized models and the undetermined generalization ability of the trained architectures. The current work tackles both issues in the radiology domain by focusing on developing an effective and interpretable cardiomegaly detection architecture based on segmentation models. The architecture consists of two distinct neural networks performing the segmentation of both cardiac and thoracic areas of a radiograph. The respective segmentation outputs are subsequently used to estimate the cardiothoracic ratio, and the corresponding radiograph is classified as a case of cardiomegaly based on a given threshold. Due to the scarcity of pixel-level labeled chest radiographs, both segmentation models are optimized in a semi-supervised manner. This results in a significant reduction in the costs of manual annotation. The resulting segmentation outputs significantly improve the interpretability of the architecture's final classification results. The generalization ability of the architecture is assessed in a cross-domain setting. The assessment shows the effectiveness of the semi-supervised optimization of the segmentation models and the robustness of the ensuing classification architecture.

Target flow deviations on the cardiopulmonary bypass cause postoperative delirium in cardiothoracic surgery-a retrospective study evaluating temporal fluctuations of perfusion data.

OBJECTIVES: Postoperative delirium (POD) is common, costly and associated with long-term morbidity and increased mortality. We conducted a cohort study to assess the contribution of cardiopulmonary bypass (CPB) to the development of POD by means of algorithm-based data processing. METHODS: A database was compiled from 3 datasets of patients who underwent cardiac surgery between 2014 and 2019: intensive care unit discharge files, CPB protocols and medical quality management records. Following data extraction and structuring using novel algorithms, missing data were imputed. Ten independent imputations were analysed by multiple logistic regression with stepwise deletion of factors to arrive at a minimal adequate model. RESULTS: POD was diagnosed in 456/3163 patients (14.4%). In addition to known demographic risk factors and comorbidities like male sex, age, carotid disease, acute kidney failure and diabetes mellitus, cardiopulmonary parameters like total blood volume at the CPB [adjusted odds ratio (AOR) 1.001; confidence interval (CI) 1.1001-1.002] were independent predictors of POD. Higher values of the minimal blood flow were associated with a lower risk of POD (AOR 0.993; CI 0.988-0.997). Flow rates at least 30% above target did emerge in the minimal adequate model as a potential risk factor, but the confidence interval suggested a lack of statistical significance (AOR 1.819; 95% CI: 0.955-3.463). CONCLUSIONS: CPB data processing proved to be a useful tool for obtaining compact information to better identify the roles of individual operational states. Strict adherence to perfusion limits along with tighter control of blood flow and acid-base balance during CPB may help to further decrease the risk of POD.