Left atrial appendage closure for stroke prevention in atrial fibrillation: current status and perspectives.

Atrial fibrillation (AF) is associated with an increased risk of stroke and systemic embolism, and the left atrial appendage (LAA) has been identified as a principal source of thromboembolism in these patients. While oral anticoagulation is the current standard of care, LAA closure (LAAC) emerges as an alternative or complementary treatment approach to reduce the risk of stroke or systemic embolism in patients with AF. Moderate-sized randomized clinical studies have provided data for the efficacy and safety of catheter-based LAAC, largely compared with vitamin K antagonists. LAA device iterations, advances in pre- and peri-procedural imaging, and implantation techniques continue to increase the efficacy and safety of LAAC. More data about efficacy and safety of LAAC have been collected, and several randomized clinical trials are currently underway to compare LAAC with best medical care (including non-vitamin K antagonist oral anticoagulants) in different clinical settings. Surgical LAAC in patients with AF undergoing cardiac surgery reduced the risk of stroke on background of anticoagulation therapy in the LAAOS III study. In this review, we describe the rapidly evolving field of LAAC and discuss recent clinical data, ongoing studies, open questions, and current limitations of LAAC.

Stretch-induced damage in endothelial monolayers.

Endothelial cells are constantly exposed to mechanical stimuli, of which mechanical stretch has shown various beneficial or deleterious effects depending on whether loads are within physiological or pathological levels, respectively. Vascular properties change with age, and on a cell-scale, senescence elicits changes in endothelial cell mechanical properties that together can impair its response to stretch. Here, high-rate uniaxial stretch experiments were performed to quantify and compare the stretch-induced damage of monolayers consisting of young, senescent, and aged endothelial populations. The aged and senescent phenotypes were more fragile to stretch-induced damage. Prominent damage was detected by immunofluorescence and scanning electron microscopy as intercellular and intracellular void formation. Damage increased proportionally to the applied level of deformation and, for the aged and senescent phenotype, induced significant detachment of cells at lower levels of stretch compared to the young counterpart. Based on the phenotypic difference in cell-substrate adhesion of senescent cells indicating more mature focal adhesions, a discrete network model of endothelial cells being stretched was developed. The model showed that the more affine deformation of senescent cells increased their intracellular energy, thus enhancing the tendency for cellular damage and impending detachment. Next to quantifying for the first-time critical levels of endothelial stretch, the present results indicate that young cells are more resilient to deformation and that the fragility of senescent cells may be associated with their stronger adhesion to the substrate.

The impact of onset-to-cut time in surgery for stable acute type a aortic dissection-a single-center retrospective cohort study.

OBJECTIVES: The study aim is to investigate the impact of onset-to-cut time on mortality in patients undergoing surgery for stable acute type A aortic dissection. METHODS: Patients who underwent surgery for acute type A aortic dissection between 01/2006 and 12/2021 and available onset-to-cut times were included. Patients with unstable aortic dissection (preoperative shock, intubation, resuscitation, coma, pericardial tamponade and local/systemic malperfusion syndromes) were excluded. After descriptive analysis, a multivariable binary logistic regression for thirty-day mortality was performed. A receiver operating characteristic curve for onset-to-cut time and thirty-day mortality was calculated. Restricted cubic splines were designed to investigate the association between onset-to-cut time and survival. RESULTS: The final cohort consisted of 362 patients. The median onset-to-cut time was 543 (376-1155) min. Thirty-day mortality was 9%. Only previous myocardial infarction (p = 0.018) and prolonged cardiopulmonary bypass time (p < 0.001) were identified as independent risk factors for thirty-day mortality. The corresponding area under the receiver operating characteristic curve showed a value of 0.49. Restricted cubic splines did not indicate an association between onset-to-cut time and survival (p = 0.316). CONCLUSIONS: Onset-to-cut time in the setting of stable acute type A aortic dissection does not seem to be a valid predictor of thirty-day mortality in patients undergoing surgery and stayed stable during the preoperative course.

Mechanical factors influence ß-catenin localization and barrier properties.

Mechanical forces are of major importance in regulating vascular homeostasis by influencing endothelial cell behavior and functions. Adherens junctions are critical sites for mechanotransduction in endothelial cells. ß-catenin, a component of adherens junctions and the canonical Wnt signaling pathway, plays a role in mechanoactivation. Evidence suggests that ß-catenin is involved in flow sensing and responds to tensional forces, impacting junction dynamics. The mechanoregulation of ß-catenin signaling is context-dependent, influenced by the type and duration of mechanical loads. In endothelial cells, ß-catenin's nuclear translocation and signaling are influenced by shear stress and strain, affecting endothelial permeability. The study investigates how shear stress, strain, and surface topography impact adherens junction dynamics, regulate ß-catenin localization, and influence endothelial barrier properties. Insight box Mechanical loads are potent regulators of endothelial functions through not completely elucidated mechanisms. Surface topography, wall shear stress and cyclic wall deformation contribute overlapping mechanical stimuli to which endothelial monolayer respond to adapt and maintain barrier functions. The use of custom developed flow chamber and bioreactor allows quantifying the response of mature human endothelial to well-defined wall shear stress and gradients of strain. Here, the mechanoregulation of ß-catenin by substrate topography, wall shear stress, and cyclic stretch is analyzed and linked to the monolayer control of endothelial permeability.

Transportation Model for Acute Aortic Dissection: Implications for Reduced Treatment Centers.

OBJECTIVES: The objective of the present study was to model the effects of a reduced number of treatment centers for acute type A aortic dissection on preclinical transportation distance and time. We examined whether treatment in selected centers in Germany would be implementable with respect to time to treatment. METHODS: For our transportation model, the number of aortic dissections and respective mean annual volume were collected from the annual quality reports (2015-2017) of all German cardiac surgery centers (n = 76). For each German postal code, the fastest and shortest routes to the nearest center were calculated using Google Maps. Furthermore, we analysed data from the German Federal Statistical Office from Jan. 2005 to Dec. 2015 to identify all surgically treated patients with acute type A aortic dissection (n = 14102) and examined the relationship between in-hospital mortality and mean annual volume of medical centers. RESULTS: Our simulation showed a median transportation distance of 27.13 km and transportation time of 35.78 min for 76 centers. Doubling the transportation time (70 min) would allow providing appropriate care with only 12 medical centers. Therefore, a mean annual volume of > 25 should be obtained. High mean annual volume was associated with significantly lower in-hospital mortality rates (p < 0.001). A significantly lower mortality rate of 14% was observed (p < 0.001) if a mean annual volume of 30 was achieved. CONCLUSIONS: Operationalising the volume-outcome relationship with fewer but larger medical centers results in lower mortality, which outweighs the disadvantage of longer transportation time.

Modelling years of life lost due to acute type A aortic dissection in the German healthcare setting: a predictive study.

OBJECTIVES: This study aimed to develop a patient-centred approach to the burden of acute type A aortic dissection (ATAAD) through modelling. The main objective was to identify potential improvements in managing this life-threatening cardiovascular condition and to provide evidence-based recommendations to optimise outcomes. DESIGN: We developed a predictive model along patient pathways to estimate the burden of ATAAD through the years of life lost (YLLs) metric. The model was created based on a systematic review of the literature and was parameterised using demographic data from the German healthcare environment. The model was designed to allow interactive simulation of different scenarios resulting from changes in key impact factors. SETTING: The study was conducted using data from the German healthcare environment and results from the literature review. PARTICIPANTS: The study included a comprehensive modelling of ATAAD cases in Germany but did not directly involve participants. INTERVENTIONS: There were no specific interventions applied in this study based on the modelling design. PRIMARY AND SECONDARY OUTCOME MEASURES: The single outcome measure was the estimation of YLL due to ATAAD in Germany. RESULTS: Our model estimated 102 791 YLL per year for ATAAD in Germany, with 62 432 and 40 359 YLL for men and women, respectively. Modelling an improved care setting yielded 93 191 YLL or 9.3% less YLL compared with the current standard while a worst-case scenario resulted in 113 023 or 10.0% more YLL. The model is accessible at https://acuteaorticdissection.com/ to estimate custom scenarios. CONCLUSIONS: Our study provides an evidence-based approach to estimating the burden of ATAAD and identifying potential improvements in the management of pathways. This approach can be used by healthcare decision-makers to inform policy changes aimed at optimising patient outcomes. By considering patient-centred approaches in any healthcare environment, the model has the potential to improve efficient care for patients suffering from ATAAD.

The role of concomitant coronary artery bypass grafting in acute type A aortic dissection complicated by coronary malperfusion.

OBJECTIVES: Managing acute type A aortic dissection with coronary malperfusion is challenging. This study outlines our revascularization strategy for these patients. METHODS: Patients undergoing surgery for acute type A aortic dissection with coronary malperfusion and aortic root involvement from January 2000 to December 2021 were included. Patients were classified using the Neri classification for coronary dissection, including a novel 'Neri -' class (no coronary dissection). Patients undergoing revascularization either as a planned or as a bailout strategy due to persisting low cardiac output were compared additionally. RESULTS: The cohort comprised 195 patients: 43 (22%) Neri -, 43 (22%) Neri A, 74 (38%) Neri B and 35 (18%) Neri C. Aortic root replacement was mainly performed in 25 Neri C patients (71%; P < 0.001). Concomitant bypass surgery was performed in 4 (9%) of Neri -, 5 (12%) of Neri A, 21 (28%) of Neri B and 32 (91%) of Neri C patients (P < 0.001). Thirty-day mortality was 42% with 21 (49%) Neri -, 12 (28%) Neri A, 30 (41%) Neri B and 19 (54%) Neri C patients (P = 0.087). Bailout revascularization was primarily performed in 11 Neri B patients (69%; P = 0.001) and associated with a higher 30-day mortality of 81% compared to 48% for planned revascularization (P = 0.042). CONCLUSIONS: Postoperative outcomes in case of coronary malperfusion are poor, irrespective of the anatomic dissection pattern. The decision for concomitant bypass surgery is crucial but may be considered in Neri C patients combined with aortic root replacement. Bailout revascularization was most common in Neri B and showed dismal outcome.

Backwash Maneuver for HeartMate3 Inflow Thrombosis: Experience From Two Cases.

The ingested pump inflow thrombus, although rare, is a potentially life-threatening complication of left ventricular assist devices. During the last years, the backwash maneuver is considered an alternative method to pump replacement for the treatment of inflow thrombosis, showing high success rate in selected patients with HeartWare HVAD devices. However, that was not the case in our present report, in which we detail the application of this method in two HeartMate3 patients with ingested pump inflow thrombus. Washing out the thrombus was not feasible in either case, possibly due to mechanical aspects of the inflow part of the HeartMate3 pump. As a result, we remain skeptical regarding the use of the method in HeartMate3 patients with inflow thrombosis.

Infectious mass debulking in lead-associated endocarditis with a percutaneous aspiration system.

AIMS: Debulking of infective mass to reduce the burden if infective material is a fundamental principle in the surgical management of infection. The aim of this study was to investigate the validity of this principle in patients undergoing transvenous lead extraction in the context of bloodstream infection (BSI). METHODS AND RESULTS: We performed an observational single-centre study on patients that underwent transvenous lead extraction due to a BSI, with or without lead-associated vegetations, in combination with a percutaneous aspiration system during the study period 2015-22. One hundred thirty-seven patients were included in the final analysis. In patients with an active BSI at the time of intervention, the use of a percutaneous aspiration system had a significant impact on survival (log-rank: P = 0.0082), while for patients with a suppressed BSI at the time of intervention, the use of a percutaneous aspiration system had no significant impact on survival (log-rank: P = 0.25). CONCLUSION: A reduction of the infective burden by percutaneous debulking of lead vegetations might improve survival in patients with an active BSI.

Microvascular dysfunction in heart transplantation is associated with altered cardiomyocyte mitochondrial structure and unimpaired excitation-contraction coupling.

INTRODUCTION: Microvascular dysfunction (MVD) is a hallmark feature of chronic graft dysfunction in patients that underwent orthotopic heart transplantation (OHT) and is the main contributor to impaired long-term graft survival. The aim of this study was to determine the effect of MVD on functional and structural properties of cardiomyocytes isolated from ventricular biopsies of OHT patients. METHODS: We included 14 patients post-OHT, who had been transplanted for 8.1 years [5.0; 15.7 years]. Mean age was 49.6 ± 14.3 years; 64% were male. Coronary microvasculature was assessed using guidewire-based coronary flow reserve(CFR)/index of microvascular resistance (IMR) measurements. Ventricular myocardial biopsies were obtained and cardiomyocytes were isolated using enzymatic digestion. Cells were electrically stimulated and subcellular Ca2+ signalling as well as mitochondrial density were measured using confocal imaging. RESULTS: MVD measured by IMR was present in 6 of 14 patients with a mean IMR of 53±10 vs. 12±2 in MVD vs. controls (CTRL), respectively. CFR did not differ between MVD and CTRL. Ca2+ transients during excitation-contraction coupling in isolated ventricular cardiomyocytes from a subset of patients showed unaltered amplitudes. In addition, Ca2+ release and Ca2+ removal were not significantly different between MVD and CTRL. However, mitochondrial density was significantly increased in MVD vs. CTRL (34±1 vs. 29±2%), indicating subcellular changes associated with MVD. CONCLUSION: In-vivo ventricular microvascular dysfunction post OHT is associated with preserved excitation-contraction coupling in-vitro, potentially owing to compensatory changes on the mitochondrial level or due to the potentially reversible cause of the disease.

Deactivation of LVAD support for myocardial recovery-surgical perspectives.

Left ventricular assist devices (LVADs) are excellent therapies for advanced heart failure patients either bridged to transplant or for lifetime use. LVADs also allow for reverse remodeling of the failing heart that is often associated with functional improvement. Indeed, growing enthusiasm exists to better understand this population of patients, whereby the LVAD is used as an adjunct to mediate myocardial recovery. When patients achieve benchmarks suggesting that they no longer need LVAD support, questions related to the discontinuation of LVAD therapy become front and center. The purpose of this review is to provide a surgical perspective on the practical and technical issues surrounding LVAD deactivation.

Mediastinal transposition of the greater omentum for treatment of infected prostheses of the ascending aorta and aortic arch.

OBJECTIVES: The aim of this study was to evaluate the outcomes of transposition of the omentum into the mediastinum to support the replacement of infected aortic grafts or to cover infected aortic grafts that are not amenable for surgical replacement. METHODS: All patients with thoracic aortic graft infections who underwent mediastinal transposition of the omentum at our institution between 2005 and 2023 were included in this study. Mediastinal transposition of the omentum was performed either after replacement of the infected graft ('curative concept') or solely as bailout procedure by wrapping the infected graft ('palliative concept'). The diagnosis, including computed tomography scans during follow-up, was made according to the criteria of the Management of Aortic Graft Infection Collaboration. RESULTS: The patient cohort consisted of 31 patients. Both in-hospital and 1-year mortality were 0% (n = 0) for the curative concept (n = 9) compared to 23% (n = 5) and 41% (n = 9) for the palliative concept (n = 22), respectively. There was no graft infection-associated death or recurrence of infection after 3 years in the curative group. Survival was 52% at 3 years in the palliative group, with freedom of infection in 59% of the patients (n = 13). CONCLUSIONS: Transposition of the omentum and wrapping of the infected aortic prosthetic graft is a useful bailout strategy for patients who are ineligible for replacement of an infected aortic graft. However, mortality stays high. For radical treatment of aortic graft infections, it may prove an effective supportive therapy and represents an important tool in the armamentarium of cardiac surgeons.

The Ascyrus Medical Dissection Stent: A One-Fits-All Strategy for the Treatment of Acute Type A Aortic Dissection?

The treatment of DeBakey type I aortic dissection remains a major challenge in the field of aortic surgery. To upgrade the standard of care hemiarch replacement, a novel device called an "Ascyrus Medical Dissection Stent" (AMDS) is now available. This hybrid device composed of a proximal polytetrafluoroethylene cuff and a distal non-covered nitinol stent is inserted into the aortic arch and the descending thoracic aorta during hypothermic circulatory arrest in addition to hemiarch replacement. Due to its specific design, it may result in a reduced risk for distal anastomotic new entries, the effective restoration of branch vessel malperfusion and positive aortic remodeling. In this narrative review, we provide an overview about the indications and the technical use of the AMDS. Additionally, we summarize the current available literature and discuss potential pitfalls in the application of the AMDS regarding device failure and aortic re-intervention.

Subcostal bilateral internal thoracic artery harvesting with the da Vinci Single Port system: an experimental feasibility study.

We evaluated the feasibility of harvesting bilateral internal thoracic arteries with the da Vinci Single Port system (SP) through a single left-sided subcostal incision. Complete bilateral mobilization with sufficiently long conduits for multivessel grafting was possible in 2 human cadavers and 2 live porcine. Creating the subcostal access and docking the SP system took between 14 and 21 min and the total harvest time ranged from 65 to 125 min in all models. No major bleeding was observed in the live porcine and hemostasis was managed with the available instrumentation. One porcine deceased during surgery due to ventricular fibrillation followed by cardiac arrest. The robotic harvesting was technically easily reproduced by the surgeons and required no additional rib-spreading. Further studies will be required to assess if this subcostal approach with the da Vinci SP system yields true clinical benefits in patients.

Transcatheter or Surgical Treatment of Aortic-Valve Stenosis.

BACKGROUND: Among low-risk patients with severe, symptomatic aortic stenosis who are eligible for both transcatheter aortic-valve implantation (TAVI) and surgical aortic-valve replacement (SAVR), data are lacking on the appropriate treatment strategy in routine clinical practice. METHODS: In this randomized noninferiority trial conducted at 38 sites in Germany, we assigned patients with severe aortic stenosis who were at low or intermediate surgical risk to undergo either TAVI or SAVR. Percutaneous- and surgical-valve prostheses were selected according to operator discretion. The primary outcome was a composite of death from any cause or fatal or nonfatal stroke at 1 year. RESULTS: A total of 1414 patients underwent randomization (701 to the TAVI group and 713 to the SAVR group). The mean (±SD) age of the patients was 74±4 years; 57% were men, and the median Society of Thoracic Surgeons risk score was 1.8% (low surgical risk). The Kaplan-Meier estimate of the primary outcome at 1 year was 5.4% in the TAVI group and 10.0% in the SAVR group (hazard ratio for death or stroke, 0.53; 95% confidence interval [CI], 0.35 to 0.79; P<0.001 for noninferiority). The incidence of death from any cause was 2.6% in the TAVI group and 6.2% in the SAVR group (hazard ratio, 0.43; 95% CI, 0.24 to 0.73); the incidence of stroke was 2.9% and 4.7%, respectively (hazard ratio, 0.61; 95% CI, 0.35 to 1.06). Procedural complications occurred in 1.5% and 1.0% of patients in the TAVI and SAVR groups, respectively. CONCLUSIONS: Among patients with severe aortic stenosis at low or intermediate surgical risk, TAVI was noninferior to SAVR with respect to death from any cause or stroke at 1 year. (Funded by the German Center for Cardiovascular Research and the German Heart Foundation; DEDICATE-DZHK6 ClinicalTrials.gov number, NCT03112980.).

A parametric study on pulse duplicator design and valve hemodynamics.

BACKGROUND: In vitro assessment is mandatory for artificial heart valve development. This study aims to investigate the effects of pulse duplicator features on valve responsiveness, conduct a sensitivity analysis across valve prosthesis types, and contribute on the development of versatile pulse duplicator systems able to perform reliable prosthetic aortic valve assessment under physiologic hemodynamic conditions. METHODS: A reference pulse duplicator was established based on literature. Further optimization process led to new designs that underwent a parametric study, also involving different aortic valve prostheses. These designs were evaluated on criteria such as mean pressure differential and pulse pressure (assessed from high-fidelity pressure measurements), valve opening and closing behavior, flow, and regurgitation. Finally, the resulting optimized setup was tested under five different hemodynamic settings simulating a range of physiologic and pathologic conditions. RESULTS: The results show that both, pulse duplicator design and valve type significantly influence aortic and ventricular pressure, flow, and valve kinematic response. The optimal design comprised key features such as a compliance chamber and restrictor for diastolic pressure maintenance and narrow pulse pressure. Additionally, an atrial reservoir was included to prevent atrial-aortic interference, and a bioprosthetic valve was used in mitral position to avoid delayed valve closing effects. CONCLUSION: This study showed that individual pulse duplicator features can have a significant effect on valve's responsiveness. The optimized versatile pulse duplicator replicated physiologic and pathologic aortic valve hemodynamic conditions, serving as a reliable characterization tool for assessing and optimizing aortic valve performance.

Permanent Pacemaker Implantation and Long-Term Outcomes of Patients Undergoing Concomitant Mitral and Tricuspid Valve Surgery.

BACKGROUND: Tricuspid valve annuloplasty (TA) during mitral valve repair (MVr) is associated with increased risk of permanent pacemaker (PPM) implantation, but the magnitude of risk and long-term clinical consequences have not been firmly established. OBJECTIVES: This study assesses the incidence rates of PPM implantation after isolated MVr and following MVr with TA as well as the associated long-term clinical consequences of PPM implantation. METHODS: State-mandated hospital discharge databases of New York and California were queried for patients undergoing MVr (isolated or with concomitant TA) between 2004 and 2019. Patients were stratified by whether or not they received a PPM within 90 days of index surgery. After weighting by propensity score, survival, heart failure hospitalizations (HFHs), endocarditis, stroke, and reoperation were compared between patients with or without PPM. RESULTS: A total of 32,736 patients underwent isolated MVr (n = 28,003) or MVr + TA (n = 4,733). Annual MVr + TA volumes increased throughout the study period (P < 0.001, trend), and PPM rates decreased (P < 0.001, trend). The incidence of PPM implantation <90 days after surgery was 7.7% for MVr and 14.0% for MVr + TA. In 90-day conditional landmark-weighted analyses, PPMs were associated with reduced long-term survival among MVr (HR: 1.96; 95% CI: 1.75-2.19; P < 0.001) and MVr + TA recipients (HR: 1.65; 95% CI: 1.28-2.14; P < 0.001). In both surgical groups, PPMs were also associated with an increased risk of HFH (HR: 1.56; 95% CI: 1.27-1.90; P < 0.001) and endocarditis (HR: 1.95; 95% CI: 1.52-2.51; P < 0.001), but not with stroke or reoperation. CONCLUSIONS: Compared to isolated MVr, adding TA to MVr was associated with a higher risk of 90-day PPM implantation. In both surgical groups, PPM implantation was associated with an increase in mortality, HFH, and endocarditis.

Temporary extracorporeal life support: single-centre experience with a new concept.

OBJECTIVES: The combination of veno-arterial extracorporeal membrane oxygenation with a micro-axial flow pump (ECMELLA) is increasingly used for cardiogenic shock (CS) therapy. We report our experience with a novel single-artery access ECMELLA setup with either femoral (2.0) or jugular venous cannulation (2.1), respectively. METHODS: Data from 67 consecutive CS patients treated with ECMELLA 2.0 (n = 56) and 2.1 (n = 11) from December 2020 and December 2022 in a tertiary cardiac center were retrospectively analyzed. RESULTS: The mean age was 60.7 ± 11 years, 56 patients (84%) were male. CS aetiology was acute on chronic heart failure (n = 35, 52%), myocardial infarction (n = 13, 19.5%), postcardiotomy syndrome (n = 16, 24%) and myocarditis (n = 3, 4.5%). Preoperatively 31 patients (46%) were resuscitated, 53 (79%) were on a ventilator and 60 (90%) were on inotropic support. The median vasoactive inotropic score was 32, and the mean arterial lactate was 8.1 mmol/l. In 39 patients (58%), veno-arterial extracorporeal membrane oxygenation was explanted after a median ECMELLA support of 4 days. Myocardial recovery was achieved in 18 patients (27%), transition to a durable left ventricular assist device in 16 (24%). Thirty-three patients (n = 33; 49%) died on support (25 on ECMELLA and 8 on Impella after de-escalation), 9 (13%) of whom were palliated. Axillary access site bleeding occurred in 9 patients (13.5%), upper limb ischaemia requiring surgical revision in 3 (4.5%). Axillary site infection occurred in 6 cases (9%), and perioperative stroke in 10 (15%; 6 hemorrhagic, 4 thromboembolic). CONCLUSIONS: ECMELLA 2.0/2.1 is a feasible and effective therapy for severe CS. The single-artery cannulation technique is associated with a relatively low rate of access-related complications.