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.

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.

Safety and efficacy of transvenous lead extraction in octogenarians using powered extraction sheaths.

BACKGROUND: In the aging population equipped with cardiac implantable electronic devices, an increasing number of octogenarians require lead extractions. This patient population is often considered as a high-risk group for surgical procedures. We, therefore, investigated the safety and efficacy of transvenous lead extraction in octogenarians using powered extraction sheaths. METHODS: Between January 2013 and March 2017, 403 patients underwent lead extraction at two high-volume lead extraction centers. A total of 71 octogenarians were treated with laser lead extraction and were included in this analysis. Primary extraction method was laser lead extraction, with additional use of mechanical rotational sheaths or femoral snares, if necessary. Patient-based and procedural data were collected and analyzed retrospectively. RESULTS: Mean age was 83.5 ± 3.3 years, 64.7% were males. A total of 152 leads were extracted. The mean lead dwell time of treated leads was 10.2 ± 5.2 years. Complete procedural success rate was 92.9%, while clinical success was achieved in 98.6%. Failure of extraction occurred in one patient (1.4%). In six (7.7%) patients, additional mechanical rotational sheaths or femoral snares were used. Overall complication rate was 4.2%, including one (1.4%) major (RA perforation) and two (2.8%) minor complications. No procedure-related mortality was observed in any of the patients. CONCLUSION: Transvenous lead extraction in octogenarians with old leads is safe and effective when performed in experienced centers. Patient's age should therefore not be considered as contraindication for lead extraction using powered extraction sheaths.

Hybrid transvenous lead extraction during cardiac surgery for valvular endocarditis.

INTRODUCTION: In patients with endocarditis and cardiac implantable electronic devices (CIED), lead extraction is recommended according to current guidelines. In patients with short lead implant duration, lead extraction by manual traction might be sufficient for intraoperative lead removal. However, in patients with long implant duration, specialized extraction tools like laser or mechanical rotational sheaths are necessary. We report our experience with transvenous lead extraction during concomitant cardiac surgery for valvular endocarditis using mechanical rotational sheaths. METHODS AND RESULTS: Between December 2018 and April 2020, 12 patients were treated with transvenous lead extraction during open-heart surgery using mechanical rotational sheaths. Cardiac surgery was performed due to mitral, aortic, or tricuspid valve endocarditis. All patient-related and procedural data were collected, and in-hospital outcome was analyzed retrospectively. Mean patients' age was 65.2 ± 16.4 years, and 75.0% were male. Nine atrial, 15 ventricular, and 2 coronary sinus leads had to be extracted. The mean time from initial lead implantation was 94.3 ± 39.7 months. Complete procedural success was achieved in all patients with no major but one minor complication (pocket hematoma) occurring during lead extraction. Four patients with pacemaker dependency received epicardial leads, seven patients were treated in a two-step approach with endocardial leads, whereas one patient had no further CIED indication. No procedure-related mortality was seen. In-hospital survival was 91.7%. CONCLUSIONS: Valvular endocarditis surgery in combination with lead extraction using mechanical rotational sheaths is safe and feasible. It results in a high procedural success rate with prompt infection control by immediate removal of all infected lead materials.

Implantable loop recorder monitoring in patients with cryptogenic stroke - Detection and treatment of different clinically relevant arrhythmias.

AIMS: Implantable loop recorders (ILR) are recommended to detect atrial fibrillation (AF) in cases of cryptogenic stroke. However, real life data besides controlled trials are rare. Aim of the study was the detection of atrial fibrillation with a special focus on other arrhythmias according to criteria defined in earlier clinical trials. METHODS: We performed a retrospective analysis of 64 patients with cryptogenic stroke who underwent ILR implantation between 4/2014 and 1/2018. The primary endpoint was the detection of atrial fibrillation, significant bradycardia (<40 bpm) or tachycardia (>150 bpm). ILR interrogation was performed after implantation and 6, 12 and 24 months thereafter. RESULTS: Mean patients age was 65.4 ± 12 years, 50% were male. Mean follow-up duration was 419.2 ± 309 days. One death occurred during follow-up. 23 patients (35.9%) experienced a symptomatic clinical neurological or cardiac event during follow-up. Overall rate of detected arrhythmias was 35% (23/64). The most frequent arrhythmia was atrial fibrillation which was observed in 16 patients (25%). 6 of 16 patients presenting with atrial fibrillation had no clinical symptoms. Bradycardias requiring subsequent pacemaker implantations were detected in 9.4%. A ventricular tachycardia was observed in one patient (1.6%). CONCLUSION: In this group of patients with cryptogenic stroke the rate of arrhythmic events was high. Besides a high rate of atrial fibrillation (25%), an unexpectedly high rate of bradyarrhythmias (9.4%) occurred in our patient collective. Since many of those episodes were clinically asymptomatic, the ILR helps to detect and treat those clinically silent arrhythmias.

Bleeding risk of submuscular ICD implantation with continued oral anticoagulation versus heparin bridging therapy.

Recent studies have shown that subcutaneous or subfascial pacemaker- and ICD implantation with continued oral anticoagulation therapy is associated with lower risk for bleeding complications, when compared to heparin bridging strategies. However, ICD generators are often implanted submuscularly. We therefore compared the bleeding risk with continued phenprocoumon therapy vs. heparin bridging in patients receiving submuscular ICD implantation. Between 01/2013 and 12/2013, 104 patients with need for oral anticoagulation received submuscular ICD or CRT-D implantation in our institution. 46 patients were implanted under continued phenprocoumon therapy while 58 patients received heparin bridging for implantation procedure. All ICD generators were placed submuscularly. The primary outcome of the study was clinically significant bleeding or device pocket hematoma with need for surgical revision. Mean patients age was 63.7 years, 72.1% were male. In patients with heparin bridging therapy, preoperative INR prior to ICD implantation was 1.2 ± 0.31 while in the group of patients on continued phenprocoumon therapy, mean pre-OP INR was 2.4 ± 0.47. In heparin bridging group, 8 (13.8%) patients experienced a clinically relevant pocket hematoma, while only 1 (2.2%) patient on continued phenprocoumon therapy needed surgical revision for pocket hematoma (P = 0.04). No further bleeding complications or clinically relevant pericardial effusion was observed in any of the groups and no perioperative thromboembolic event occurred. Submuscular ICD implantation under continued phenprocoumon therapy was safe and feasible. Compared to patients with heparin bridging therapy, those with continued phenprocoumon therapy had a lower incidence of clinically relevant bleeding complications.

Pulse wave analysis of the aortic pressure waveform in patients with vasovagal syncope.

Vascular reflex mechanisms contribute to vasovagal syncope. However, the alterations in central haemodynamics in patients with vasovagal syncope are unknown. 30 consecutive patients (36.5 ± 15 years, 14 females) with recurrent vasovagal syncope (VVS) and a positive tilt table test were compared to 39 age- and sex-matched controls (36.9 ± 16 years, 15 females) with a negative tilt table result and no history of syncope. Central aortic pressure parameters including augmentation index and central pulse pressure as markers of aortic stiffness were generated non-invasively by applanation tonometry of the radial artery and use of a validated mathematical transfer function. No difference in aortic augmentation index was observed between groups. (VVS 9 ± 2.6 vs. Control 11 ± 2.4, p = 0.8). However, in patients with vasovagal syncope the aortic pressure waveform significantly differed from healthy controls. A prolonged time to the peak of aortic pressure wave (aortic T2) was observed in patients with vasovagal syncope (226 ± 24 vs. 208 ± 21 ms, p = 0.001). Furthermore time to the first shoulder of the aortic pressure wave (aortic T1) was slightly shorter compared to healthy controls, but did not reach statistical significance (106 ± 22 vs. 110 ± 12 ms, p = 0.33). Patients with vasovagal syncope have an altered aortic pressure waveform at rest, but no signs of elevated aortic stiffness. The underlying mechanisms for these findings may potentially result from a complex imbalance of the autonomic nervous system with a continuous deregulation of the sympathetic and parasympathetic reflex arcs.

Clinical experience of combined HeartWare ventricular assist device and implantable cardioverter defibrillator therapy.

INTRODUCTION: The HeartWare continuous flow ventricular assist device (HVAD) is used in an increasing number of heart failure patients. In those patients, ventricular arrhythmias (VAs) are common and, consequently, many patients already have an implanted implantable cardioverter defibrillator (ICD) in place or receive ICD implantation after left ventricular assist device implantation. However, limited data on feasibility and necessity of combined ICD and HVAD therapy are available. In this study we present our technical and clinical experience. METHODS AND RESULTS: Between 01/2010 and 06/2013, 41 patients received HVAD implantation. Twenty-six HVAD patients who already had an ICD device placed prior to HVAD implantation or received ICD implantation afterwards were enrolled in this study. Peri- and postoperative complications as well as ICD interrogations were documented and analyzed retrospectively. Mean patients age was 58.4 ± 12.6 years; 88.5% of patients were male. During mean follow-up of 12.2 ± 8.9 months, appropriate ICD interventions occurred in 9 patients (34.6%) due to ventricular tachyarrhythmia (n = 7) or ventricular fibrillation (n = 2). An inappropriate ICD intervention was seen in 1 patient (3.9%) due to tachycardic atrial fibrillation. Patients on HVAD with a history of VAs (n = 13) had a significantly higher incidence of ICD interventions compared to patients with primary prophylactic indication for ICD (n = 13; 53.8% vs. 7.7%; P = 0.015). No disturbance of ICD function was seen after HVAD implantation. CONCLUSION: Combined ICD and HVAD therapy was safe and feasible, without electromagnetic interference between ICD and ventricular assist device. The incidence of ICD interventions was high in patients with a history of VAs, but low in patients with ICD implantation for primary prevention.

Efficacy of prophylactic intra-aortic balloon pump therapy in chronic heart failure patients undergoing cardiac surgery.

This study investigated the efficacy of prophylactic intraoperative intra-aortic balloon pump (IABP) usage in chronic heart failure patients with severely reduced left ventricular function undergoing elective cardiac surgery. Between January 2008 and December 2012, 107 patients with severely reduced left ventricular ejection fraction (LVEF <35%) received prophylactic intraoperative IABP implantation during open-heart surgery. Surgical procedures performed were isolated coronary artery bypass grafting (CABG) in 35 patients (32.7%), aortic valve replacement in 12 (11.2%), mitral valve repair or replacement in 15 (14.0%), combined valve and CABG procedures in 27 (25.2%), and other surgical procedures in 18 (16.8%). Results and outcomes were compared with those in a propensity score-matched cohort of 107 patients who underwent cardiac surgery without intraoperative IABP implantation. Matching criteria were age, gender, LVEF, and surgical procedure. Duration of intensive care unit (ICU) stay, duration of hospital stay, and 30-day mortality were markers of outcome. In the IABP group, mean patient age was 69.1 ± 13.7 years; 66.4% (70) were male. All IABPs were placed intraoperatively. Mean duration of IABP application time was 42.4 ± 8.7 h. IABP-related complications occurred in five patients (4.7%), including one case of inguinal bleeding, one case of mesenteric ischemia, and ischemia of the lower limb in three patients. No stroke or major bleeding occurred during IABP support. Mean durations of ICU and hospital stay were 3.38 ± 2.15 days and 7.69 ± 2.02 days, respectively, in the IABP group, and 4.20 ± 3.14 days and 8.57 ± 3.26 days in the control group, showing statistically significant reductions in duration of ICU and hospital stay in the IABP group (ICU stay, P = 0.036; hospital stay, P = 0.015). Thirty-day survival rates were 92.5 and 94.4% in the IABP and control group, respectively, showing no statistically significant difference (P = 0.75). IABP usage in chronic heart failure patients with severely reduced LVEF undergoing cardiac surgery was safe and resulted in shorter ICU and hospital stay but did not influence 7- and 30-day survival rates.

Implantation of a right ventricular implantable cardioverter-defibrillator lead in the right ventricular outflow tract in a patient with Ebstein anomaly and right ventricular lead dislocation.

An 80-year-old patient with Ebstein anomaly and prior implantable cardioverter-defibrillator (ICD) implantation was sent to our heart center because of right ventricular (RV)-ICD lead dislocation. Positioning of the new RV lead was difficult, no stable position could be found, and sensing and threshold measurements showed weak results in the RV basis, apex, and septum. So, we conducted positioning of the lead in the RV outflow tract where a stable position with good sensing and threshold parameters was found.

Efficacy of four different left atrial appendage closure techniques during cardiac surgery-A transesophageal echocardiography follow-up study.

Objective: Closure of the left atrial appendage (LAA) is a routine part of atrial fibrillation ablation surgery and significantly reduces stroke rates. Different LAA-closure techniques are used in cardiac surgery with variable results reported. We therefore evaluated the efficacy of 4 different LAA-closure techniques in patients undergoing cardiac surgery. Methods: In total, 149 patients who underwent concomitant LAA closure during cardiac surgery between 2015 and 2019 were included in this retrospective transesophageal echocardiography study. Four different LAA-closure techniques were evaluated: LAA clipping (n = 62), suture ligation (n = 28), stapler resection (n = 30), and surgical LAA excision (n = 29). Successful LAA closure was defined as absence of LAA perfusion and absence of a stump greater than 10 mm. Results: The mean patients age was 68.7 ± 9.4 years; 61.7% were male. No complications related to LAA closure were observed. Mean follow-up was 36.5 ± 8 months. Transesophageal echocardiography follow-up showed the following LAA closure success rates: LAA clip 98.4%, surgical excision 93.1%, stapler resection 76.6%, and suture ligation 39.2%. Suture ligation resulted in a high rate of recanalization (50%) and residual stumps (10.8%), whereas stapler resection resulted in a high rate of residual stumps (23.4%). Overall, 4 patients (2.7%) had a stroke during follow-up. In detail, 2 of 27 (7.4%) patients with unsuccessful LAA closure had a stroke, whereas 2 of the 122 (1.6%) patients with successful LAA closure had a stroke. Conclusions: In our study, LAA clipping and surgical LAA excision proved to be both successful LAA-closure methods. External LAA ligation and stapler resection resulted in low rates of successful LAA closure and should be avoided.

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.

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.

Transcutaneous lead implantation connected to an externalized pacemaker in patients with implantable cardiac defibrillator/pacemaker infection and pacemaker dependency.

AIMS: Systemic cardiac implantable electronic device (CIED) infection is a serious complication, especially in patients with pacemaker (PM) dependency. In those patients after infectious device removal temporary pacing is necessary, to obtain adequate haemodynamics. In this study, a new therapy option with temporary pacing by ipsilateral implantation of a new active-fixation right ventricular (RV)-lead was evaluated. METHODS AND RESULTS: Between September 2009 and November 2011, infectious lead removal was performed in 17 patients with systemic CIED infection. Temporary pacing was achieved by simultaneous implantation of a new active-fixation RV-lead, which then was connected extracorporally to the old CIED device. Antibiotic therapy was initiated. When laboratory infection parameters were in normal range and blood culture samples showed negative results, new CIED was implanted on contralateral side and temporary RV-lead was removed. Mean patients' age was 71.3 ± 9.1 years. Mean C-reactive protein values were 79.3 mg/dL, and mean leucocytes counts were 12.6 × 10(3). After lead extraction, temporary pacing was necessary in all patients due to severe bradycardia. Mean duration of temporary pacing was 12.7 (6-24) days. No major procedure-related peri- or post-operative adverse events occurred. Mean time of hospitalization was 20.8 (10-48) days. Mean follow-up time was 21.1 months (12-36), showing survival rate of 100% and freedom from reinfection in all patients. CONCLUSION: Ipsilateral implantation of a temporary active-fixation RV-lead connected to an externalized PM and pursued antibiotic therapy seems to be a good option for patients with CIED infection and PM dependency, showing no temporary pacing-related complications and no reinfection after mean follow-up time of 21.1 months.

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.

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.

Prognostic impact of implantable cardioverter defibrillators and associated adverse events in patients with continuous flow left ventricular assist devices.

Objectives: Implantation of implantable cardioverter defibrillators (ICD) reduces the risk of all-cause mortality in symptomatic heart failure (HF) patients with severe left ventricular (LV) dysfunction. Nevertheless, the prognostic impact of ICD therapy in continuous flow left ventricular assist device (LVAD) recipients remains controversial. Methods: 162 consecutive HF patients, who underwent LVAD implantation at our institution between 2010 and 2019, were categorized according to the presence (n = 94, ICD-group) or absence (n = 68, Control-group) of ICDs. Apart from clinical baseline and follow-up parameters, adverse events (AEs) related to ICD therapy and overall survival rates were retrospectively analyzed. Results: Out of 162 consecutive LVAD recipients 79 patients (48.8%) were preoperatively categorized as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile ≤2. The prevalence of severe HF symptoms and preoperative use of short-term circulatory support devices (54.4% vs. 13.8%, p < 0.001) was higher within the Control-group, although baseline severity of LV and RV dysfunction was similar. Apart from an increased prevalence of perioperative right heart failure (RHF) within the Control-group (45.6% vs. 17.0%; p < 0.001), procedural characteristics and perioperative outcome were similar. Overall-survival during a median follow-up of 14 (3.0-36.5) months was similar within both groups (p = 0.46). During the first 2 years after LVAD implantation 53 ICD-related AEs occurred within the ICD-group. Thereof, lead-dysfunction occurred in 19 patients and unplanned ICD-reintervention in 11 patients. Furthermore, in 18 patients appropriate shocks without loss of consciousness occurred, whereas inappropriate shocks occurred in 5 patients. Conclusion: ICD therapy in LVAD recipients was not associated with a survival benefit or reduced morbidity after LVAD implantation. Conservative ICD-programming seems to be justified to avoid ICD-related complications and "awake shocks" after LVAD implantation.

Laser Lead Extraction During Venoarterial ECMO support.

The treatment of valvular endocarditis in patients with cardiac implantable electrophysiological device (CIED) includes valvular surgery and lead extraction. This can be challenging in patients with severely reduced left ventricular ejection fraction (LVEF). Reduced LVEF in combination with sepsis and cardioplegic cardiac arrest can make weaning from cardiopulmonary bypass difficult. Some of these patients require venoarterial extracorporeal membrane oxygenation (VA-ECMO) for postcardiotomy syndrome. Lead extraction by manual traction is often not possible in cases with a long lead dwell time. Therefore, a lead extraction procedure with powered sheaths is required during the VA-ECMO support. We describe our technique for laser lead extraction during VA-ECMO support in a 64-year-old patient with triple valve endocarditis and lead vegetations.

Bacterial membrane vesicle functions, laboratory methods, and applications.

Bacterial membrane vesicles (BMVs) are cupped-shaped structures formed by bacteria in response to environmental stress, genetic alteration, antibiotic exposure, and others. Due to the structural similarities shared with the producer organism, they can retain certain characteristics like stimulating immune responses. They are also able to carry molecules for long distances, without changes in the concentration and integrity of the molecule. Bacteria originally secrete membrane vesicles for gene transfer, excretion, cell to cell interaction, pathogenesis, and protection against phages. These functions are unique and have several innovative applications in the pharmaceutical industry that have attracted both scientific and commercial interest.This led to the development of efficient methods to artificially stimulate vesicle production, purification, and manipulation in the lab at nanoscales. Also, for specific applications, engineering methods to impart pathogen antigens against specific diseases or customization as cargo vehicles to deliver payloads to specific cells have been reported. Many applications of BMVs are in cancer drugs, vaccines, and adjuvant development with several candidates in clinical trials showing promising results. Despite this, applications in therapy and commercialization stay timid probably due to some challenges one of which is the poor understanding of biogenesis mechanisms. Nevertheless, so far, BMVs seem to be a reliable and cost-efficient technology with several therapeutic applications. Research toward characterizing more membrane vesicles, genetic engineering, and nanotechnology will enable the scope of applications to widen. This might include solutions to other currently faced medical and healthcare-related challenges.

Safety and efficacy of transvenous lead extraction of very old leads.

OBJECTIVES: Transvenous lead extraction using mechanical rotational- or laser sheaths is an established procedure. Lead dwell time has been recognized as a risk factor for extraction failure and procedure-related complications. We therefore investigated the safety and efficacy of transvenous extraction of leads with an implant duration of more than 10 years. METHODS: Between January 2013 and March 2017, a total of 403 patients underwent lead extraction in 2 high-volume lead extraction centres. One hundred and fifty-four patients with extraction of at least 1 lead aged over 10 years were included in this analysis. Laser lead extraction was the primary extraction method, with additional use of mechanical rotational sheaths or femoral snares, if necessary. All procedural- and patient-based data were collected into a database and retrospectively analysed. RESULTS: Mean patient's age was 65.8 ± 15.8 years, 68.2% were male. Three hundred and sixty-two leads had to be extracted. The mean lead dwell time of treated leads was 14.0 ± 6.1 years. Complete procedural success was achieved in 91.6% of cases, while clinical success was achieved in 96.8%. Failure of extraction occurred in 3.2%. Leads that could not be completely removed had a significantly longer lead dwell time (18.2 vs 13.2 years; P = 0.016). Additional mechanical rotational sheaths or femoral snares were used in 26 (16.9%) patients. Overall complication rate was 4.6%, including 5 (3.3%) major and 2 (1.3%) minor complications. There was no procedure-related mortality. CONCLUSIONS: Transvenous lead extraction in leads aged over 10 years is safe and effective when performed in specialized centres and with use of multiple tools and techniques. Leads that could not be completely extracted had a statistically significant longer lead dwell time.