Evaluation of cell survival in different 3D-printed geometric shapes of human iPSC-derived engineered heart tissue.

OBJECTIVES: Engineered Heart Tissue (EHT) is a promising tool to repair heart muscle defects and can additionally be used for drug testing. Due to the absence of an in vitro vascularization, EHT geometry crucially impacts nutrient and oxygen supply by diffusion capacity. We analyzed cardiomyocyte survival in different EHT geometries. METHODS: Different geometries with varying surface-area-to-volume-ratios were calculated (structure A (Ring) AS/V = 58.47 mm2/440 µL3, structure B (Infinity) 25.86 mm2/440 µL3). EHTs were generated from hiPSC-derived cardiomyocytes (4 × 106) and a fibrin/thrombin hydrogel. Cell viability was evaluated by RT-PCR, cytometric studies, and Bioluminescence imaging. RESULTS: Using 3D-printed casting molds, spontaneously beating EHTs can be generated in various geometric forms. At day 7, the RT-PCR analyses showed a significantly higher Troponin-T value in ring EHTs, compared to infinity EHTs. In cytometric studies, we evaluated 15% more Troponin-T positive cells in ring (73% ± 12%), compared to infinity EHTs (58% ± 11%, p = 0.04). BLI visualized significantly higher cell survival in ring EHTs (ROI = A: 1.14 × 106 p/s and B: 8.47 × 105 p/s, p < 0.001) compared to infinity EHTs during longitudinal cultivation process. CONCLUSION: Use of 3D-printing allows the creation of EHTs in all desired geometric shapes. The geometry with an optimized surface-area-to-volume-ratio (ring EHT) demonstrated a significantly higher cell survival measured by RT-PCR, Bioluminescence imaging, and cytometric studies using FACS analysis.

Left atrial strain predicts the rhythm outcome in patients with persistent atrial fibrillation undergoing left atrial cryoablation during minimally invasive mitral valve repair.

Objectives: Patients with atrial fibrillation (AF) have lower left atrial (LA) strain, which is a predictor for LA function. Here, we evaluated the prognostic value of LA strain to predict the rhythm outcome in patients with persistent AF undergoing LA cryoablation concomitant to minimally invasive mitral valve repair. Methods: Between 01/2016 and 12/2020, 72 patients with persistent AF underwent LA cryoablation during minimally invasive mitral valve surgery. All patients received a complete LA lesion set and left atrial appendage (LAA) closure with a clip. All patients received preoperative transthoracic echocardiography (TTE) with LA and left ventricular strain measurements. Preoperative LA and LV strain analysis was correlated with postoperative rhythm outcome. Results: The mean age of the patients was 66.9 ± 7.2 years, of whom 42 (58%) were male patients. No major ablation-related complications occurred in any of the patients. Successful LAA closure was confirmed by intraoperative echocardiography in all patients. The 1-year survival rate was 97%. Freedom from AF at 12 months was 72% and 68% off antiarrhythmic drugs. Preoperative LA strain values were statistically significantly higher in patients with freedom from AF at 12 months of follow-up (12.7% ± 6.9% vs. 4.9% ± 4.1%, p = 0.006). Preoperative LV strain value was not associated with postoperative rhythm outcome. In multivariate logistic regression analysis, LA strain (p < 0.001) and AF duration (p = 0.017) were predictors for freedom from AF at 12 months of follow-up. Conclusions: In our study, LA strain analysis predicted the rhythm outcome in patients with persistent AF undergoing concomitant surgical AF ablation. In the future, LA strain might be a useful tool to guide decision-making on ablation strategies in patients with persistent AF.

Bionic Nanocoating of Prosthetic Grafts Significantly Reduces Bacterial Growth.

Prosthetic materials are a source of bacterial infections, with significant morbidity and mortality. Utilizing the bionic "Lotus effect," we generated superhydrophobic vascular prostheses by nanocoating and investigated their resistance to bacterial colonization. Nanoparticles were generated from silicon dioxide (SiO2), and coated vascular prostheses developed a nanoscale roughness with superhydrophobic characteristics. Coated grafts and untreated controls were incubated with different bacterial solutions including heparinized blood under mechanical stress and during artificial perfusion and were analyzed. Bioviability- and toxicity analyses of SiO2 nanoparticles were performed. Diameters of SiO2 nanoparticles ranged between 20 and 180 nm. Coated prostheses showed a water contact angle of > 150° (mean 154 ± 3°) and a mean water roll-off angle of 9° ± 2°. Toxicity and viability experiments demonstrated no toxic effects of SiO2 nanoparticles on human induced pluripotent stem cell-derived cardiomyocytes endothelial cells, fibroblasts, and HEK239T cells. After artificial perfusion with a bacterial solution (Luciferase+ Escherichia coli), bioluminescence imaging measurements showed a significant reduction of bacterial colonization of superhydrophobic material-coated prostheses compared to that of untreated controls. At the final measurement (t = 60 min), a 97% reduction of bacterial colonization was observed with superhydrophobic material-coated prostheses. Superhydrophobic vascular prostheses tremendously reduced bacterial growth. During artificial perfusion, the protective superhydrophobic effects of the vascular grafts could be confirmed using bioluminescence imaging.

Aortic Valve Repair Results in Better 1-Year Survival Than Replacement: Results From German Aortic Valve Registry.

BACKGROUND: Aortic valve (AV) repair is an evolving surgical strategy in the treatment of nonelderly adults with aortic regurgitation. We aimed to determine the 1-year outcome after AV repair vs surgical AV replacement (sAVR) using real-world data from the German Aortic Valve Registry. METHODS: A total of 8076 aortic regurgitation patients (mean age, 59.1 ± 15.0 years; 76% men; mean The Society of Thoracic Surgeons score, 1.3 ± 1.1), who underwent AV surgical procedures between 2011 and 2015, were identified from German Aortic Valve Registry. The AV was repaired in 2327 patients (29%), and the remaining 5749 patients (71%) underwent sAVR. A weighted propensity score model, including the variables of age, sex, and The Society of Thoracic Surgeons score, was used to correct for baseline differences between AV repair and sAVR cohorts. The primary end point was 1-year survival after AV repair vs sAVR. Secondary end points were freedom from cardiac events and AV reinterventions. RESULTS: Survival at 1 year was 97.7% (95% CI, 97.0%-98.5%) in the AV repair cohort vs 96.4% (95% CI, 95.9%-96.9%) in the propensity score-weighted sAVR cohort (log-rank P < .001). Cox regression revealed a significant advantage of AV repair vs sAVR (hazard ratio, 0.68; 95% CI, 0.51-0.90; P < .0001) on 1-year survival, which was independent of age. Cardiac event-free survival at 1 year was 85.7% (95% CI, 483.8%-87.7%) in the AV repair group vs 81.7% (95% CI, 80.7%-82.9%) in the sAVR group (log-rank P < .001). AV reintervention was required in 38 AV repair patients (1.6%) compared with 1.6% in the sAVR cohort (P = .59). CONCLUSIONS: AV repair surgery, whenever intraoperatively feasible, is associated with a significantly better 1-year survival and 1-year cardiac event-free survival compared with sAVR.

Hemodynamics and Diastolic Function after Native Aortic Valve Preserving vs. Replacing Surgery.

BACKGROUND: Alterations in left ventricular (LV) diastolic function following native tissue-preserving aortic valve (AV) procedures have not been systematically investigated. Furthermore, no comparisons have been made between these changes and those observed after prosthetic AV replacement. METHODS: From October 2017 to August 2020, 74 patients aged <65 years were referred to our institution for elective AV surgery. Preoperative and postoperative (i.e., discharge, 3-month and 1-year follow-up) transthoracic echocardiography was analyzed. RESULTS: Native tissue-preserving surgery was performed in 55 patients (AV repair: n = 42, Ross procedure: n = 13). The remaining 19 patients underwent prosthetic AV replacement. Preoperatively and at discharge, transvalvular hemodynamics and LV diastolic function were comparable in both groups. At 1-year follow-up, native valve (NV) patients showed significantly lower mean transvalvular gradient (7 ± 5 vs. 9 ± 3 mmHg, p = 0.046) and peak velocity (1.74 ± 0.51 vs. 2.26 ± 0.96 m/s, p = 0.004), and significantly better septal e' (9.1 ± 2.7 vs. 7.7 ± 2.5 cm/s, p = 0.043) and lateral e' (14.7 ± 3.1 vs. 11.7 ± 3.7 cm/s, p = 0.001). From preoperatively to 1-year postoperatively, septal and lateral e' and E/e' improved markedly after NV preservation (septal e': +0.7 cm/s, p = 0.075; lateral e': +2.3 cm/s, p < 0.001; E/e': -1.5, p = 0.001) but not after AV replacement (septal e': +0.2 cm/s, p = 0.809; lateral e': +0.8 cm/s, p = 0.574; E/e': -1.2, p = 0.347). Significant negative linear correlations between postoperative transvalvular gradients and absolute changes in lateral e' and E/e' were detected during follow-up. CONCLUSION: Preservation of native tissue in AV surgery results in superior transvalvular hemodynamics compared with prosthetic AV replacement. This may induce faster LV reverse remodeling and may explain more pronounced improvement in LV diastolic function.

Cardiac T1 mapping enables risk prediction of LV dysfunction after surgery for aortic regurgitation.

Background: To assess whether cardiac T1 mapping for detecting myocardial fibrosis enables preoperative identification of patients at risk for early left ventricular dysfunction after surgery of aortic regurgitation. Methods: 1.5 Tesla cardiac magnetic resonance imaging was performed in 40 consecutive aortic regurgitation patients before aortic valve surgery. Native and post-contrast T1 mapping was performed using a modified Look-Locker inversion-recovery sequence. Serial echocardiography was performed at baseline and 8 ± 5 days after aortic valve surgery to quantify LV dysfunction. Receiver operating characteristic analysis was performed to determine the diagnostic accuracy of native T1 mapping and extracellular volume for predicting postoperative LV ejection fraction decrease >-10% after aortic valve surgery. Results: Native T1 was significantly increased in patients with a postoperatively decreased LVEF (n = 15) vs. patients with a preserved postoperative LV ejection fraction (n = 25) (i.e., 1,071 ± 67 ms vs. 1,019 ± 33 ms, p = .001). Extracellular volume was not significantly different between patients with preserved vs. decreased postoperative LV ejection fraction. With a cutoff-of value of 1,053 ms, native T1 yielded an area under the curve (AUC) of .820 (95% CI: .683-.958) for differentiating between patients with preserved vs. reduced LV ejection fraction with 70% sensitivity and 84% specificity. Conclusion: Increased preoperative native T1 is associated with a significantly higher risk of systolic LV dysfunction early after aortic valve surgery in aortic regurgitation patients. Native T1 could be a promising tool to optimize the timing of aortic valve surgery in patients with aortic regurgitation to prevent early postoperative LV dysfunction.

Correlation of Myocardial Native T1 and Left Ventricular Reverse Remodeling after Valvular Surgery.

Myocardial native T1 is a known cardiovascular magnetic resonance (CMR) imaging biomarker to quantify diffuse myocardial fibrosis in valvular cardiomyopathy. We hypothesized that diffuse myocardial fibrosis assessed by preoperative T1 mapping might correlate with LV reverse remodeling after valvular surgery. A prospective monocentric cohort study was conducted including 79 consecutive patients with valvular cardiomyopathy referred for surgical treatment of severe aortic or severe functional mitral regurgitation. Native T1 values were assessed by CMR before surgery. LV geometry parameters (i.e., LVEDV, LVESV) were obtained by 2D transthoracic echocardiography before and six months after surgery. Postoperative change of LV geometry parameters was calculated as delta (∆) variable (i.e., six months value minus baseline value). Mean native T1 was 1047 ± 39 ms, mean ∆LVEDV was -33 ± 42 mL, and mean ∆LVESV was -15 ± 27 mL. Native T1 values correlated with ∆LVEDV (Pearson r = 0.29; p = 0.009) and ∆LVESV (Pearson r = 0.29; p = 0.015). Native T1 values < 1073 ms were identified as independent predictor of postoperative reduction of LVEDV (HR 3.0; 95%-CI: 1.1-8.0; p = 0.03) and LVESV (HR 2.9; 95%-CI: 1.1-7.4; p = 0.03). Diffuse myocardial fibrosis assessed by myocardial native T1 correlates with LV reverse remodeling at six months after valvular surgery. T1 mapping may be a valuable tool to predict LV reverse remodeling in valvular heart disease.

Valvular Cardiomyopathy in Aortic Valve Regurgitation Correlates with Myocardial Fibrosis.

Objective: At the tissue level, disruption of the extracellular matrix network leads to irreversible cardiac fibrosis, which contributes to myocardial dysfunction. At the myocyte level, downregulation of beta-adrenoceptors (beta-AR) reduces adaptation to increased workload. The aim of our study was to analyse the correlation between myocardial fibrosis and beta-AR sensitivity in patients with aortic valve (AV) disease. Methods: A total of 92 consecutive patients who underwent elective AV surgery between 2017-2019 were included in our study (51 with aortic regurgitation (AR-group); 41 with aortic stenosis (AS-group) and left ventricular (LV) biopsies were obtained intraoperatively. In vitro force contractility testing was performed by measuring beta-AR sensitivity (-log EC50[ISO]). In parallel, a quantitative analysis of myocardial fibrosis burden was performed. Results: Mean age at the time of AV surgery was not statistically different in both groups (AR: 53.3 ± 15.3 years vs. AS: 58.7 ± 17.0 years; p = 0.116). The LV end-diastolic diameter was significantly enlarged in the AR-group when compared to the AS-group (59.4 ± 15.6 vs. 39.7 ± 21.2; p < 0.001). Analysis of beta-AR sensitivity (AR: -6.769 vs. AS: -6.659; p = 0.316) and myocardial fibrosis (AR: 8.9% vs. AS: 11.3%; p = 0.284) showed no significant differences between patients with AS and AR. There was no correlation between myocardial fibrosis and beta-AR sensitivity in the whole study cohort (R = 0.1987; p = 0.100) or in the AS-subgroup (R = 0.009; p = 0.960). However, significant correlation of fibrosis and beta-AR sensitivity was seen in AR-patients (R = 0.363; p = 0.023). Conclusion: More severe myocardial fibrosis was associated with reduced beta-AR sensitivity in patients presenting with AR but not with AS. Therefore, our results suggest that in patients with AR, cellular myocardial dysfunction is present and correlates with the extent of myocardial fibrosis in the myocardium.

Physical and Mental Recovery after Aortic Valve Surgery in Non-Elderly Patients: Native Valve-Preserving Surgery vs. Prosthetic Valve Replacement.

Background: Exercise capacity and patient-reported outcomes are increasingly considered crucial following aortic valve (AV) surgery in non-elderly adults. We aimed to prospectively evaluate the effect of native valve preservation compared with prosthetic valve replacement. Methods: From October 2017 to August 2020, 100 consecutive non-elderly patients undergoing surgery for severe AV disease were included. Exercise capacity and patient-reported outcomes were evaluated upon admission, and 3 months and 1 year postoperatively. Results: In total, 72 patients underwent native valve-preserving procedures (AV repair or Ross procedure, NV group), and 28 patients, prosthetic valve replacement (PV group). Native valve preservation was associated with an increased risk of reoperation (weighted hazard ratio: 10.57 (95% CI: 1.24-90.01), p = 0.031). The estimated average treatment effect on six-minute walking distance in NV patients at 1 year was positive, but not significant (35.64 m; 95% CI: -17.03-88.30, adj. p = 0.554). The postoperative physical and mental quality of life was comparable in both groups. Peak oxygen consumption and work rate were better at all assessment time points in NV patients. Marked longitudinal improvements in walking distance (NV, +47 m (adj. p < 0.001); PV, +25 m (adj. p = 0.004)) and physical (NV, +7 points (adj. p = 0.023); PV, +10 points (adj. p = 0.005)) and mental quality of life (NV, +7 points (adj. p < 0.001); PV, +5 points (adj. p = 0.058)) from the preoperative period to the 1-year follow-up were observed. At 1 year, there was a tendency of more NV patients reaching reference values of walking distance. Conclusions: Despite the increased risk of reoperation, physical and mental performance markedly improved after native valve-preserving surgery and was comparable to that after prosthetic aortic valve replacement.

The impact of a standardized Enhanced Recovery After Surgery (ERAS) protocol in patients undergoing minimally invasive heart valve surgery.

BACKGROUND: An enhanced recovery after surgery (ERAS) protocol is a multimodal and multi-professional strategy aiming to accelerate postoperative convalescence. Pre-, intra- and postoperative measures might furthermore reduce postoperative complications and hospital length of stay (LOS) in a cost-effective way. We hypothesized that our unique ERAS protocol leads to shorter stays on the intensive care unit (ICU) and a quicker discharge without compromising patient safety. METHODS: This retrospective single center cohort study compares data of n = 101 patients undergoing minimally invasive heart valve surgery receiving a comprehensive ERAS protocol and n = 111 patients receiving routine care. Hierarchically ordered primary endpoints are postoperative hospital length of stay (LOS), postoperative complications and ICU LOS. RESULTS: Patients risk profiles and disease characteristics were comparably similar. Age was relevantly different between the groups (56 (17) vs. 57.5 (13) years, p = 0.015) and therefore adjusted. Postoperative LOS was significantly lower in ERAS group (6 (2) days vs. 7 (1) days, p<0.01). No significant differences, neither in intra- or postoperative complications, nor in the number of readmissions (15.8% vs. 9.9%, p = 0.196) were shown. In hospital LOS (7 (3) days vs. 8 (4) days, p<0.01) and ICU LOS (18.5 (6) hours vs. 26.5 (29) hours, p<0.01) a considerable difference was shown. CONCLUSION: The ERAS protocol for minimally invasive heart valve surgery is safe and feasible in an elective setting and leads to a quicker hospital discharge without compromising patient safety. However, further investigation in a randomized setting is needed.

Minimally invasive epicardial left-ventricular lead implantation and simultaneous left atrial appendage closure.

Background: Atrial fibrillation (AF) is common in patients with heart failure resulting in a high prevalence of AF in patients receiving Cardiac Resynchronization Therapy (CRT) implantation. In patients, unsuitable for transvenous left ventricular (LV)-lead implantation, epicardial LV-lead implantation represents a valuable alternative. Epicardial LV-lead placement can be achieved totally thoracoscopical or via minimally invasive left lateral thoracotomy. In patients with atrial fibrillation, concomitant left atrial appendage (LAA) clipping is feasible via the same access. Therefore, the aim of our study was the analysis of safety and efficacy of epicardial LV lead implantation and concomitant LAA clipping via minimally invasive left-lateral thoracotomy. Methods: Between December 2019 and March 2022, 8 patients received minimally invasive left atrial LV-lead implantation with concomitant LAA closure using the AtriClip. Transesophageal echocardiography (TEE) was performed to intraoperatively guide and control LAA closure. Results: Mean patients age was 64 ± 11.2 years, 67% were male patients. Minimally invasive left-lateral thoracotomy was used in 6 patients while a totally thoracoscopic approach was performed in 2 cases. Epicardial lead implantation was successfully performed in all patients with good pacing threshold (mean 0.8 ± 0.2 V) and sensing values (10.1 ± 2.3 mV). Posterolateral position of the LV lead was achieved in all patients. Furthermore, successful LAA closure was confirmed during TEE in all patients. No procedure-related complications occurred in any of the patients. Two patients additionally received simultaneous laser lead extraction during the same procedure. Complete lead extraction was achieved in both patients. All patients were extubated in the OR and had an uneventful postoperative course. Conclusion: Our study highlights a novel treatment approach for patients with atrial fibrillation and the necessity of epicardial LV leads. Placement of a posterolateral LV lead position with concomitant occlusion of the left atrial appendage via a minimally-invasive left-lateral thoracotomy or even a totally thoracoscopic approach is safe and feasible with superior cosmetic result and complete occlusion of the left atrial appendage.

Proteomic Analysis in Valvular Cardiomyopathy: Aortic Regurgitation vs. Aortic Stenosis.

Left ventricular (LV) reverse remodeling after aortic valve (AV) surgery is less predictable in chronic aortic regurgitation (AR) than in aortic stenosis (AS). We aimed to disclose specific LV myocardial protein signatures possibly contributing to differential disease progression. Global protein profiling of LV myocardial samples excised from the subaortic interventricular septum in patients with isolated AR or AS undergoing AV surgery was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry. Based on label-free quantitation protein intensities, a logistic regression model was calculated and adjusted for age, sex and protein concentration. Web-based functional enrichment analyses of phenotype-associated proteins were performed utilizing g:Profiler and STRING. Data are available via ProteomeXchange with identifier PXD039662. Lysates from 38 patients, including 25 AR and 13 AS samples, were analyzed. AR patients presented with significantly larger LV diameters and volumes (end-diastolic diameter: 61 (12) vs. 48 (13) mm, p < 0.001; end-diastolic volume: 180.0 (74.6) vs. 92.3 (78.4), p = 0.001). A total of 171 proteins were associated with patient phenotype: 117 were positively associated with AR and the enrichment of intracellular compartment proteins (i.e., assigned to carbohydrate and nucleotide metabolism, protein biosynthesis and the proteasome) was detected. Additionally, 54 were positively associated with AS and the enrichment of extracellular compartment proteins (i.e., assigned to the immune and hematopoietic system) was observed. In summary, functional enrichment analysis revealed specific AR- and AS-associated signatures of LV myocardial proteins.

Radiographic and clinical outcome of tibial plateau fractures treated with bone allograft.

BACKGROUND: To determine the clinical outcome of patients who had been treated with bone allografts during open reduction and internal fixation (ORIF) of tibial head fractures. METHODS: Patients who suffered a medial, lateral, or bicondylar fracture of the tibial plateau and underwent surgical treatment by open reduction and internal fixation (ORIF) using human femoral head bone allografts were included. Patients were invited to provide information for the following: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol Five Dimension score (EQ-5D), Lower Extremity Functional Scale (LEFS) and Parker Mobility Score. Bone mineral density (BMD) of the allograft area and the healthy human bone tissue were measured by quantitative computed tomography. RESULTS: A total of 22 patients with a mean follow-up time of 2.88 ± 2.46 years were included in our study. The most common fractures observed in this study were classified as Schatzker II (11 patients, 50.0%) or AO/OTA 41.B3 (12 patients, 54.5%) fractures. Postoperative WOMAC total was 13.0 (IQR = 16.3, range 0-33). Median quality of life (EQ-5D) score was 0.887 ± 0.121 (range 0.361-1.000). Median Lower Extremity Functional Scale (LEFS) score was 57.5 ± 19.0 (range 33-79). Mean Parker Mobility Score was 9 (range 6-9). Median bone mineral density (BMD) for the whole group was 300.04 ± 226.02 mg/cm3 (range - 88.68 to 555.06 mg/cm3) for region of interest (ROI 5) (central), 214.80 ± 167.45 mg/cm3 (range - 7.16 to 597.21 mg/cm3) for ROI 1-4 (marginal zones: medial, lateral, ventral, dorsal) and 168.14 ± 65.54 mg/cm3 (range 17.47-208.97 mg/cm3) for healthy bone tissue (femur and tibia). CONCLUSION: Based on WOMAC scores, LEFS, ambulatory status, and quality of life findings, it can be concluded that following tibial head ORIF with allograft bone patients has promising results.

Rare Presentation of Sinus of Valsalva Aneurysm Treated by Aortic Valve Reimplantation Technique

Abstract Sinus of Valsalva aneurysm is a rare cardiac abnormality which can be acquired or of congenital origin. A spontaneous rupture into the right atrium is possible and, if not adequately treated, may result in a progressive heart failure due to the left-to-right intracardiac shunt. If ruptured sinus of Valsalva aneurysm is diagnosed, surgical repair is indicated, and different surgical techniques have been reported. If concomitant aortic regurgitation is present, aortic valve replacement is usually performed. Herein, we describe an uncommon clinical presentation of a ruptured sinus of Valsalva aneurysm which has been corrected by aortic valve reimplantation.

Complete Left-Atrial Lesion Set versus Pulmonary Vein Isolation Only in Patients with Paroxysmal AF Undergoing CABG or AVR.

Background and Objectives: In patients with paroxysmal atrial fibrillation (AF) undergoing CABG or aortic valve surgery, many surgeons are not willing to open the left atrium to perform a complete left-sided Cox-Maze lesion set. Pulmonary vein isolation (PVI) is often favored in those patients. We investigated the outcome of patients with isolated pulmonary vein isolation compared to those receiving an extended left atrial (LA) lesion set. Materials and Methods: Between 2003 and 2016, 817 patients received concomitant surgical AF ablation in our institution. A total of 268 patients with paroxysmal AF were treated by surgical ablation concomitant to AVR or CABG. Of those, 86 patients underwent a complete left-sided lesion set, while 182 patients were treated with an isolated pulmonary vein isolation. The primary endpoint was freedom from atrial fibrillation at 12 months' follow-up. Results: There were no statistically significant differences regarding baseline characteristics. No major ablation-related complications were observed in any of the groups. In the PVI group, three patients (1.6%) had an intraoperative stroke, while two (2.3%) patients experienced a stroke in the LA ablation group (p = 0.98). In-hospital mortality was 3.4% in the PVI group, and 2.8% in the extended LA group (p = 0.33). Freedom from AF at 12 months' follow-up was 76% in the extended LA ablation group and 70% in the PVI group, showing no statistically significant difference (p = 0.32). Conclusion: Surgical AF ablation concomitant to CABG or AVR in patients with paroxysmal AF is safe and effective. There was no statistically significant difference between the compared lesion sets in terms of freedom from AF, survival or stroke rate after 12 months.

Antegrade axillary arterial perfusion in 3D endoscopic minimally-invasive mitral valve surgery.

Background: Minimally-invasive (MIS) mitral valve (MV) surgery has become standard therapy in many cardiac surgery centers. While femoral arterial perfusion is the preferred cannulation strategy in MIS mitral valve surgery, retrograde arterial perfusion is known to be associated with an increased risk for cerebral atheroembolism, particularly in atherosclerosis patients. Therefore, antegrade perfusion may be beneficial in such cases. This analysis aimed to compare outcomes of antegrade axillary vs. retrograde femoral perfusion in the MIS mitral valve surgery. Methods: This analysis includes 50 consecutive patients who underwent MIS between 2016 and 2020 using arterial cannulation of right axillary artery (Group A) due to severe aortic arteriosclerosis. Perioperative outcomes of the study group were compared with a historical control group of retrograde femoral perfusion (Group F) which was adjusted for age and gender (n = 50). Primary endpoint of the study was in-hospital mortality and perioperative cerebrovascular events. Results: Patients in group A had a significantly higher perioperative risk as compared to Group F (EuroSCORE II: 3.9 ± 2.5 vs. 1.6 ± 1.5; p = 0.001; STS-Score: 2.1 ± 1.4 vs. 1.3 ± 0.6; p = 0.023). Cardiopulmonary bypass time (group A: 172 ± 46; group F: 178 ± 51 min; p = 0.627) and duration of surgery (group A: 260 ± 65; group F: 257 ± 69 min; p = 0.870) were similar. However, aortic cross clamp time was significantly shorter in group A as compared to group F (86 ± 20 vs. 111 ± 29 min, p < 0.001). There was no perioperative stroke in either groups. In-hospital mortality was similar in both groups (group A: 1 patient; group F: 0 patients; p = 0.289). In group A, one patient required central aortic repair due to intraoperative aortic dissection. No further cardiovascular events occurred in Group A patients. Conclusion: Selective use of antegrade axillary artery perfusion in patients with systemic atherosclerosis shows similar in-hospital outcomes as compared to lower risk patients undergoing retrograde femoral perfusion. Patients with higher perioperative risk and severe atherosclerosis can be safely treated via the minimally invasive approach with antegrade axillary perfusion.

Outcomes of surgical bioprosthetic aortic valve replacement for aortic insufficiency.

BACKGROUND: Results and durability of aortic valve replacement in aortic stenosis are well known, but no study has focused on the results of aortic valve replacement in aortic insufficiency. AIM: The aim of this retrospective study was to describe our mid-term outcomes after aortic valve replacement for aortic insufficiency. METHODS: All consecutive adult patients who underwent bioprosthetic aortic valve replacement for aortic insufficiency at two European centres (in France and Germany) between May 2005 and December 2020 were analysed. RESULTS: During the study period, 289 patients were included. Mean age was 56.9±12.5 years. Overall operative mortality was 1.5%, and the 10-year survival estimate rate was 75.0%, which was significantly lower than in the age- and sex-matched general population, with a standardized mortality ratio of 2.88 (95% confidence interval 1.96-4.08; P<0001). Freedom from aortic valve-related death was 87.6%, and from aortic valve-related reoperation was 87.4%. No patient aged>60 years was reoperated on during follow-up. Freedom from severe structural valve deterioration at 10 years was 73.3%, and freedom from moderate structural valve deterioration at 10 years was 50.3%. Freedom from major adverse valve-related events at 10 years was 69.7%. CONCLUSIONS: Although bioprosthetic aortic valve replacement for aortic insufficiency shows good early results, 10-year mortality and major adverse valve-related event rates in young patients may be a concern, with a reduction in life expectancy compared with the general population.

Outcomes of aortic valve repair: early results from the German Aortic Valve Registry.

OBJECTIVES: Aortic valve (AV) repair is an evolving surgical strategy in the treatment of young patients with aortic regurgitation (AR) and/or aortic root aneurysm. We aimed to determine the clinical outcome following AV repair/AV-sparing root surgery using real-world data from the German Aortic Valve Registry. METHODS: A total of 2327 patients with AR (mean age 55.2 ± 15.0 years, 76% men), who underwent AV repair/AV-sparing root surgery between 2011 and 2015 (i.e. 5% of 42 868 AV surgery patients enrolled in the German Aortic Valve Registry during the same period) were included. Study cohort was subdivided according to the technique of AV repair: isolated AV repair without root surgery (group I) (n = 914), AV-sparing root surgery (i.e. reimplantation or remodelling) without cusp repair (group II) (n = 1077) and AV-sparing root surgery (i.e. reimplantation or remodelling) with simultaneous cusp repair (group III) (n = 336). Primary end point was 1-year survival after AV repair/AV-sparing root surgery. Secondary end points were freedom from cardiac adverse events and freedom from AV reinterventions at 1-year follow-up. RESULTS: Thirty-day mortality was 19 (0.8%) in the whole study cohort without significant differences in the 3 subgroups [4 (0.4%) patients in group I vs 14 (1.3%) patients in group II vs 1 (0.3%) patient in group III (P = 0.054)]. Postoperatively, 1445 (74%) patients had no residual AR, 474 (24%) patients had mild AR and 40 (2%) patients had moderate/severe AR at the time of hospital discharge. One-year survival (95% confidence interval) was 97.7% (97.1-98.3) in the whole study cohort and without significant difference among the 3 subgroups. One-year cardiac adverse event-free survival (95% confidence interval) was 85.7% (84.2-87.1) and was similar in all 3 study groups in propensity score-weighted analysis. A total of 38 (1.6%) patients required AV reintervention during a 1-year follow-up, without significant difference among subgroups (P = 0.11). CONCLUSIONS: AV repair/AV-sparing root surgery is performed in 5% of patients requiring AV surgery in Germany. Our data demonstrate very satisfactory periprocedural and 1-year survival and cardiac event-free survival after AV repair surgery. Implementation of specific surgical techniques during the index procedure seems to result in comparable outcomes.

Regulation of APD and Force by the Na+/Ca2+ Exchanger in Human-Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue.

The physiological importance of NCX in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is not well characterized but may depend on the relative strength of the current, compared to adult cardiomyocytes, and on the exact spatial arrangement of proteins involved in Ca2+ extrusion. Here, we determined NCX currents and its contribution to action potential and force in hiPSC-CMs cultured in engineered heart tissue (EHT). The results were compared with data from rat and human left ventricular tissue. The NCX currents in hiPSC-CMs were larger than in ventricular cardiomyocytes isolated from human left ventricles (1.3 ± 0.2 pA/pF and 3.2 ± 0.2 pA/pF for human ventricle and EHT, respectively, p < 0.05). SEA0400 (10 µM) markedly shortened the APD90 in EHT (by 26.6 ± 5%, p < 0.05) and, to a lesser extent, in rat ventricular tissue (by 10.7 ± 1.6%, p < 0.05). Shortening in human left ventricular preparations was small and not different from time-matched controls (TMCs; p > 0.05). Force was increased by the NCX block in rat ventricle (by 31 ± 5.4%, p < 0.05) and EHT (by 20.8 ± 3.9%, p < 0.05), but not in human left ventricular preparations. In conclusion, hiPSC-CMs possess NCX currents not smaller than human left ventricular tissue. Robust NCX block-induced APD shortening and inotropy makes EHT an attractive pharmacological model.