Toll-like Receptor Signaling Rewires Macrophage Metabolism and Promotes Histone Acetylation via ATP-Citrate Lyase.

Toll-like receptor (TLR) activation induces inflammatory responses in macrophages by activating temporally defined transcriptional cascades. Whether concurrent changes in the cellular metabolism that occur upon TLR activation influence the quality of the transcriptional responses remains unknown. Here, we investigated how macrophages adopt their metabolism early after activation to regulate TLR-inducible gene induction. Shortly after TLR4 activation, macrophages increased glycolysis and tricarboxylic acid (TCA) cycle volume. Metabolic tracing studies revealed that TLR signaling redirected metabolic fluxes to generate acetyl-Coenzyme A (CoA) from glucose resulting in augmented histone acetylation. Signaling through the adaptor proteins MyD88 and TRIF resulted in activation of ATP-citrate lyase, which in turn facilitated the induction of distinct LPS-inducible gene sets. We postulate that metabolic licensing of histone acetylation provides another layer of control that serves to fine-tune transcriptional responses downstream of TLR activation. Our work highlights the potential of targeting the metabolic-epigenetic axis in inflammatory settings.

Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series.

BACKGROUND: Transcriptomic data on bronchoalveolar lavage (BAL) from COVID-19 patients are currently scarce. OBJECTIVES: This case series seeks to characterize the intra-alveolar immunopathology of COVID-19. METHOD: BALs were performed on 14 patients (5 COVID-19, of which 3 mild and 2 largely asymptomatic, 9 controls). Controls included asthma (n = 1), unremarkable BALs (n = 3), infections with respiratory syncytial virus (n = 1), influenza B (n = 1), and infections with other coronaviruses (n = 3). SARS-CoV-2 RNA load was measured by quantitative nucleic acid testing, while the detection of other pathogens was performed by immunofluorescence or multiplex NAT. RESULTS: Gene expression profiling showed 71 significantly downregulated and 5 upregulated transcripts in SARS-CoV-2-positive lavages versus controls. Downregulated transcripts included genes involved in macrophage development, polarization, and crosstalk (LGALS3, MARCO, ERG2, BTK, RAC1, CD83), and genes involved in chemokine signaling and immunometabolism (NUPR1, CEBPB, CEBPA, PECAM1, CCL18, PPARG, ALOX5, ALOX5AP). Upregulated transcripts featured genes involved in NK-T cell signaling (GZMA, GZMH, GNLY, PRF1, CD3G). Patients with mild COVID-19 showed a significant upregulation of genes involved in blood mononuclear cell/leukocyte function (G0S2, ANXA6, FCGR2B, ADORA3), coagulation (von Willebrand factor [VWF]), interferon response (IFRD1, IL12RB2), and a zinc metalloprotease elevated in asthma (CPA3) compared to asymptomatic cases. In-silico comparison of the 5 COVID-19 BAL cases to a published cohort of lethal COVID-19 showed a significant upregulation of "antigen processing and presentation" and "lysosome" pathways in lethal cases. CONCLUSIONS: These data underscore the heterogeneity of immune response in COVID-19. Further studies with a larger dataset are required to gain a better understanding of the hallmarks of SARS-CoV-2 immunological response.

Antibacterial copper-filled TiO2 coating of cardiovascular implants to prevent infective endocarditis-A pilot study.

BACKGROUND: Infective endocarditis (IE) poses a significant health risk, especially in patients with prosthetic heart valves. Despite advances in treatment, mortality rates remain high. This study aims to investigate the antibacterial properties of a copper titanium dioxide (4× Cu-TiO2) coating on cardiovascular implants against Staphylococcus aureus, a common causative agent of IE. METHODS: Titanium oxide carriers functionalized with copper ions were employed as an antibacterial coating for heart and vascular prostheses. The coating's antibacterial efficacy was assessed using S. aureus ATCC 29213. Microscopic evaluations were conducted on both biological and artificial materials. Antibacterial activity was qualitatively assessed via a modified disc diffusion method and quantitatively measured through colony counts in NaCl suspensions. RESULTS: The coating process was successfully applied to all tested cardiovascular prosthetic materials. Qualitative assessments of antibacterial effectiveness revealed an absence of bacterial growth in the area directly beneath the coated valve. Quantitative evaluations showed a significant reduction in bacterial colonization on coated mechanical valves, with 2.95 × 104 CFU per valve, compared to 1.91 × 105 CFU in control valves. CONCLUSIONS: The 4× Cu-TiO2 coating demonstrated promising antibacterial properties against S. aureus, suggesting its potential as an effective strategy for reducing the risk of bacterial colonization of cardiovascular implants. Further studies are needed to assess the longevity of the coating and its efficacy against other pathogens.

Outcomes of modular cable exchange in HeartMate 3 patients versus conventional driveline repair in HeartMate II patients.

BACKGROUND: Driveline (DL) damages are a common difficulty among ventricular assist devices (VAD). Repairing the electrical fibers inside the DL on a running pump is hazardous and requires technical expertise, which is not easily available on site. A new feature of the HeartMate3 (Abbott, U.S.A.) LVAD is a modular driveline that allows an easy exchange of the DL cord. In this report we analyze our experiences with this feature. METHODS: We performed a retrospective analysis of 302 patients who underwent either HeartMate II or HeartMate 3 implantation between February 2004 and September 2021. Patients were screened for driveline faults and need for exchange or repair of driveline or VAD exchange. Documented were baseline characteristics, reasons for DL or VAD exchange, and complications. Follow-up was three months after the procedure. RESULTS: We present a cohort of 302 patients who underwent either HMII (n = 107;35.4%) or HM 3 (n = 195; 64.5%) implantation. Out of those, 40 patients (40/302; 13.2%) required driveline repair (DLRe) or exchange (DLEx). Out of 107 HMII patients, 9 showed severe DL damages (9/107; 8.4%). Six patients (6/9; 66.6%) underwent DLRe, two patients (2/6; 33.3%) required VAD exchange after DLRe, one patient (1/2;50%) experienced emergency VAD exchange after pump stop. The DLRe procedure in the other four patients (4/6; 66.6%) was successful. Due to damage to the internal driveline two patients (2/9; 22.2%) underwent emergency device exchange and one patient (1/9;11.1%) was listed for transplantation. 31 out 195 HM3 patients underwent exchange of the modular DL. In none of the cases, damages of the internal fibers were the reasons for the exchange. In 100% of the cases, damages of the external coating were the reason for DL exchange. In none of the cases, complications occurred after the exchange procedure. CONCLUSIONS: Driveline damages are a habitual, recurrent complication in VAD patients. The exchange of the modular driveline cable of the HM3 is feasible and safe compared to the conventional DL repair in HMII patients. Risky repair attempts and surgical LVAD exchange due to major damages of the electrical fibers can be avoided successfully by the new feature of HM3 driveline.

Clinical characteristics and long-term outcomes in patients with peripartum cardiomyopathy (PPCM) receiving left ventricular assist devices (LVAD).

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure (HF), presenting with left ventricular (LV) systolic dysfunction either at the end of pregnancy or in the months following delivery. In rare cases, PPCM leads to severe impairment of LV function, refractory cardiogenic shock or advanced HF. LV assist devices (LVAD) have been shown to be a feasible treatment option in advanced HF. However, little is known about long-term outcomes and prognosis of PPCM patients undergoing LVAD implantation. METHODS: A retrospective analysis of data from PPCM patients undergoing LVAD implantation in two tertiary centers with respect to long-term outcomes was performed. RESULTS: Twelve patients of median age 30 (18-39) years were included. Eight patients were experiencing cardiogenic shock (INTERMACS 1) at implantation. Seven patients were implanted within 1 month of their PPCM diagnosis. Median duration of LVAD support was 19 (2-92) months with median follow up of 67 (18-136) months (100% complete). In-hospital and 1-year mortality were 0% and 8.3%, respectively. Two patients died on LVAD support, four patients were successfully bridged to transplantation, two patients are still on LVAD, and four were successfully weaned due to sufficient LV recovery (one died after LV function deteriorated again). CONCLUSION: LVAD treatment of decompensated end-stage PPCM is feasible. Early LVAD provision led to hemodynamic stabilization in our cohort and facilitated safe LV recovery in one third of these young female patients.

Microembolic signal monitoring in patients with HeartMate 3 and HeartWare left ventricular assist devices: Association with antithrombotic treatment and cerebrovascular events.

BACKGROUND: In patients with left ventricular assist devices (LVADs), ischemic and hemorrhagic stroke are dreaded complications. Predictive markers for these events are lacking. This study aimed to investigate the prevalence and predictive value of microembolic signals (MES) for stroke, detected by Transcranial Doppler sonography (TCD) in patients with HeartMate 3 (HM 3) or HeartWare (HW). METHODS: A thirty-minute bilateral TCD monitoring of the middle cerebral artery (MCA) was performed in 62 outpatients with LVAD (HM 3 N = 31, HW N = 31) and 31 healthy controls. Prevalence and quantity of MES were investigated regarding clinical and laboratory parameters. Cerebrovascular events (CVE) were recorded on follow-up at 90 and 180 days. RESULTS: MES were detected in six patients with HM 3, three patients with HW, and three controls. Within the LVAD groups, patients on monotherapy with vitamin-K-antagonist (VKA) without antiplatelet therapy were at risk for a higher count of MES (negative binomial regression: VKA: 1; VKA + ASA: Exp(B) = 0.005, 95%CI 0.001-0.044; VKA + clopidogrel: Exp(B) = 0.012, 95%CI 0.002-0.056). There was no association between the presence of MES and CVE or death on follow-up (p > 0.05). CONCLUSION: For the first time, the prevalence of MES was prospectively investigated in a notable outpatient cohort of patients with HM 3 and HW. Despite optimized properties of the latest LVAD, MES remain detectable depending on antithrombotic therapy. No association between MES and CVE could be detected.

Expanding the Minimally Invasive Approach towards the Ascending Aorta-A Practical Overview of the Currently Available Techniques.

Minimally invasive techniques have gained immense importance in cardiovascular surgery. While minimal access strategies for coronary and mitral valve surgery are already widely accepted and often used as standard approaches, the application of minimally invasive techniques is currently expanded towards more complex operations of the ascending aorta as well. In this new and developing field, various techniques have been established and reported ranging from upper hemisternotomy approaches, which allow even extensive operations of the ascending aorta to be performed through a minimally invasive access to sternal sparing thoracotomy strategies, which completely avoid sternal trauma during ascending aorta replacements. All of these techniques place high demands on patient selection, preoperative planning, and practical surgical implementation. Application of these strategies is currently limited to high-volume centers and highly experienced surgeons. This narrative review gives an overview of the currently available techniques with a special focus on the practical execution as well as the advantages and disadvantages of the currently available techniques. The first results demonstrate the practicability and safety of minimally invasive techniques for replacement of the ascending aorta in a well-selected patient population. With success and complication rates comparable to classic full sternotomy, the proof of concept for minimally invasive replacement of the ascending aorta is now achieved.

Biocompatibility of an apical ring plug for left ventricular assist device explantation: Results of a feasibility pre-clinical study.

BACKGROUND: Patients receiving left ventricle assist devices (LVADs) as bridge to recovery remain a minority with 1%-5% of LVADs explanted after improvement of myocardial function. Nevertheless, considering the growing population of patients supported with LVADs, an increasing demand of new explantation strategies is expected in the near future. A novel plug for LVAD explantation has been developed and its biocompatibility profile needs to be proved. This study tested the biocompatibility of this novel plug in an in vivo ovine model. METHODS: Six adult Blackhead Persian female sheep received plug implantation on the cardiac apex via minimally invasive approach and were clinically observed up to 90 days. Echocardiography was performed to detect thrombus formation or further plug-related complications. After the observation period, euthanasia was performed and samples including the plug and the surrounding tissues were obtained to be analyzed with correlative light and electron microscopy. Organ necrosis, ischemia and peripheral embolism were investigated. RESULTS: Three animals survived surgery and completed the follow-up time without experiencing clinical complications. Echocardiographic controls excluded the presence of an intracavitary thrombus in the left ventricle (LV). Autopsy confirmed no signs of local infection, LV thrombus or peripheral embolism. Light and electron microscopy revealed an intact epithelium covering a layer of connective tissue on the plug surface facing the heart lumen. CONCLUSIONS: This novel apical plug for LVAD explantation allows for endothelial and connective tissue growth on its ventricular side within 90 days from surgery. Further studies are required to fully demonstrate the biocompatibility of this apical plug and investigate the optimal anticoagulation regimen to be applied after implantation.

Is there a sex gap in outcomes of comparable patients supported with left ventricular assist devices?

OBJECTIVES: Historically, females were described as suffering from worse outcomes after left ventricular assist device (LVAD) implantation. However, females' preoperative conditions are unique, making direct comparisons with males challenging. This study aimed to select through propensity score (PS) matching two preoperatively comparable populations of females and males and test if any real sex-related difference exists regarding survival and adverse events after LVAD implantation. METHODS: This retrospective single-center observational study investigated patients who received LVAD implantation between 2010 and 2018. PS matching was applied to balance preoperative heterogeneity between males and females. Primary endpoint was survival at follow-up. Secondary endpoints included perioperative outcomes and LVAD-related adverse events. RESULTS: 92 fully comparable females(n = 46) and males(n = 46) were selected after PS matching (median age:57 years, min-max:18-75). 26.1% of patients required preoperative mechanical circulatory support. Females needed more intraoperative fresh frozen plasma (p < 0.001) and platelets transfusions (p = 0.008) compared to males, but postoperative outcomes were comparable between groups. In-hospital, 1 and 2-year survival were 78.3%, 69.6% and 65.2%, respectively, with no differences between groups. Survival probability remained comparable up to 8 years of follow-up (p = 0.35). Overall, females showed a higher rate of strokes (p = 0.039) compared to males in the follow-up time. CONCLUSIONS: After reducing preoperative heterogeneity between females and males, survival after LVAD implantation does not differ based on sex. However, differences might exist in terms of higher transfusions and strokes in females. Reducing preoperative sex disparities and developing intraoperative and anticoagulation strategies which acknowledge sex-related variations might help abolishing differences in LVAD outcomes.

Mitochondrial metabolism in macrophages.

Mitochondria are considered to be the powerhouse of the cell. Normal functioning of the mitochondria is not only essential for cellular energy production but also for several immunomodulatory processes. Macrophages operate in metabolic niches and rely on rapid adaptation to specific metabolic conditions such as hypoxia, nutrient limitations, or reactive oxygen species to neutralize pathogens. In this regard, the fast reprogramming of mitochondrial metabolism is indispensable to provide the cells with the necessary energy and intermediates to efficiently mount the inflammatory response. Moreover, mitochondria act as a physical scaffold for several proteins involved in immune signaling cascades and their dysfunction is immediately associated with a dampened immune response. In this review, we put special focus on mitochondrial function in macrophages and highlight how mitochondrial metabolism is involved in macrophage activation.

Left ventricular assist device implantation in patients with left ventricular thrombus.

An intra-cavitary left ventricular (LV) thrombus is a relative contraindication to LV assist device (LVAD) implantation based on increased thromboembolic risks. Herein, we present our experience with LVAD patients with or without preoperative diagnosis of LV-thrombus. We retrospectively investigated 563 patients who received LVAD implantation between 2004 and 2018. Diagnosis of LV-thrombus was verified with computed tomography scan, magnetic resonance imaging, echocardiography, or intraoperative LV inspection. The primary endpoint was 30-day survival free of stroke and pump thrombosis. Overall, 72 patients (12.8%) had a diagnosis of LV-thrombus. They were younger (51 years; IQR:41-59), affected by severely reduced ejection fraction (15%; IQR:10-20), more often presenting with dilated cardiomyopathy (61.8%) and INTERMACS profile 1 (33.3%). Preoperative atrial fibrillation was frequent in patients without LV-thrombus (38.9%). Conventional sternotomy was the preferred approach in LV-thrombus patients (77.8%), based on more HMII implantations in these patients (41.7%). Survival free of strokes and pump thrombosis at 30 days was comparable (P = .5751) between patients with (83.3%) or without LV-thrombus (80.9%). LVAD implantation in patients with preoperative LV-thrombus is safe and feasible. When managed through correct diagnostic and intraoperative strategies including accurate inspection of the LV cavity, these patients show similar 30-day outcomes compared to patients without LV-thrombus.

Prophylactic mechanical circulatory support for protected ventricular tachycardia ablation: A meta-analysis of the literature.

Acute hemodynamic decompensation (AHD) during ventricular tachycardia (VT) ablation occurs in about 11% of cases. Prophylactic use of temporary mechanical circulatory support (pro-tMCS) has been applied to prevent AHD during VT ablation, but evidence supporting this practice is still lacking. This systematic review and meta-analysis assessed the procedural characteristics and outcomes of pro-tMCS for VT ablation. PubMed/Medline was screened until February 2020. Articles including adults receiving pro-tMCS for VT ablation were included, and a meta-analysis to compare proMCS and no-tMCS was performed. Primary outcome was in-hospital/30-day mortality. Five observational studies presenting 400 procedures (pro-tMCS: n = 187; no-tMCS: n = 213) were included. Baseline characteristics were comparable between groups. Impella and TandemHeart were used in 86.6% and 13.4% of cases, respectively. In the pro-tMCS group, more VTs were induced (mean difference: 0.52, confidence interval [CI]: 0.26-0.77, P < .0001), and patients remained in VT on average for 24.04 minutes longer (CI: 18.28-29.80, P < .00001). Procedural success was comparable between groups, as was VT recurrence. Pro-tMCS patients had an odds ratio of 0.55 (CI: 0.28-1.05, P = .07) for in-hospital/30-day mortality and 0.55 (CI: 0.32-0.94, P = .03) for mortality at follow-up. Sixty-four percent of no-tMCS patients received rescue tMCS. The most common tMCS-related complications were bleeding events. Pro-tMCS allowed for a prolonged time on VTs and the induction of more VTs. Although these advantages were not associated with differences in procedural success, VT recurrence, or in-hospital/30-day mortality in the overall population, pro-tMCS might improve long-term survival. Further prospective studies are urgently needed to confirm these results.

Flying after left ventricular assist device implantation.

Literature on the air travel activities of patients supported by permanent mechanical assist devices is rare. To the best of our knowledge, no air travel guidelines or fitness prerequisites exist on whether and when ventricular assist device (VAD) patients are allowed to travel by plane after device implantation. In this study, we evaluated the topic of air travel after VAD implantation. This working group aimed to produce a report on air travel passengers supported by VADs, regarding their fitness to fly. Fifty left ventricular assist device (LVAD) patients were surveyed in a worldwide multicenter study. The single survey was performed with a multimethod design, including interviews conducted face-to-face, online, and on phone. Out of 50 patients, 97% described their traveling by aircraft as perfect and uneventful during the flight. Eighty-five percent of the study participants consulted their medical practitioner before the flight. No patient reported the occurrence of a severe condition associated with flying. LVAD alarms, especially low flow alarms, did not occur in any of the devices. Thirty-five percent of the surveyed patients, however, stated a major problem pertaining to the security check procedures at the airport. The results of this study suggest that commercial air travel is safe for stable patients on permanent VAD support and traveling can be resumed securely after VAD implantation. Conscientious preparation by packing necessary devices, fluids, medications, and careful preparation for the airport security check is recommended.

Out of hospital management of LVAD patients during COVID-19 outbreak.

Coronavirus disease 2019 (COVID-19) is a pandemic touching thousands of people all around the world. Patients supported with left ventricular assist devices (LVADs) are affected by long-standing cardiovascular diseases and subjected to variations of the normal cardiovascular physiology, thus requiring an even closer monitoring during the COVID-19 outbreak. Nevertheless, the COVID-19 pandemic led to a drastic reduction in routine clinical activities and a consequent risk of looser connections between LVAD patients and their referring center. Potential deleterious effects of such a situation can be a delayed recognition of LVAD-related complications, misdiagnosis of COVID-19, and impaired social and psychological well-being for patients and families. As one of the largest LVAD programs worldwide, we designed a sustainable and enforceable telemonitoring algorithm which can be easily adapted to every LVAD center so as to maintain optimal quality of care for LVAD patients during the COVID-19 pandemic.

Driving After Left Ventricular Assist Device Implantation.

Literature on driving capacities of ventricular assist device patients is rare and driving restrictions differ from center to center. Currently, no guidelines exist on whether and when left ventricular assist device (LVAD) patients are allowed to begin driving cars after device implantation. In this study, we assess the driving abilities of patients after LVAD implantation. Three hundred and ninety LVAD patients have been surveyed in a worldwide, multicenter study. The single survey followed a multi-method design, including online, phone, and face-to-face interviews. Out of 390 patients, 72% are still driving and 28% did not continue driving after LVAD implantation. Reasons for discontinuation were capability (24%), insecurity (17%), and disapproval by family members (9%) or doctors (5%). Ninety percent of the patients describe their ability to drive as perfect or adequate. Sixty-nine percent state that they are not restricted in their general driving capacity. Forty-nine percent report not to be restricted in agility to drive by the device equipment. The majority of patients have not been involved in car accidents or major complications (94%). Eight accidents were reported (3%). Out of those, all were minor collisions. No patient reported the occurrence of a fatal accident or casualties. LVAD alarms did occur in six incidents (2%) with the majority being low battery alarms. The results of this study suggest that driving with a left ventricular assist device is safe for stable patients and driving can be resumed 3 months after LVAD implantation after careful patient assessment.

In Vitro Evaluation of Inflow Cannula Fixation Techniques in Left Ventricular Assist Device Surgery.

The therapy of terminal heart failure with left ventricular assist devices has become a standard in cardiac surgery. Yet the surgical implantation technique is not standardized and differs from center to center. Complications associated with left ventricular assist device (LVAD) inflow cannula placement are thrombosis, suction events, and flow disturbances. Within this in vitro study we aimed to investigate if the fixation technique of the sewing ring has an impact on the position of the inflow cannula. For this in vitro study the HeartMate III LVAD (Thoratec Corporation, Pleasanton, CA, USA) was used. In five sessions, two approaches were considered for coring of the ventricle for LVAD inflow cannula insertion: "sew-then-core" and "core-then-sew." In the "sew-then-core" technique, the sewing cuff is first affixed to the heart, usually with 8-16 interrupted pledgeted mattress sutures. Subsequently, a cylindrical knife is used to resect a cylindrical core of myocardium to permit cannula insertion. In the "core-then-sew" technique, the sequence is reversed such that the knife is used before the suture ring is affixed. When the "sew-then-core" technique is used, the mattress sutures may be placed with full-thickness bites that penetrate the endocardium (i.e., transmural stitching) or partial-thickness bites that do not penetrate the endocardium (i.e., epicardial stitching). When the "core-then-sew" technique is used, the suture is passed fully into the ventricular lumen and fed back through the cored hole, at which point the needle may be reinserted into the freshly cored myocardium such that it exits the epicardium (i.e., transmural stitching with back stitch) or not (i.e., transmural stitching without back stitch). These four different sewing ring fixation suturing techniques were tested by experienced surgeons to affix the sewing ring: transmural stitching, epicardial stitching, transmural stitching with back stitch, and transmural stitching without back stitch. The sewing ring was sewed onto a silicone dummy designed to simulate the left ventricle with standard 2-0 Ethibond sutures (Ethicon, Somerville, NY, USA). Afterward, the dummies were measured and documented via photography. In addition, porcine hearts were used to simulate the suturing techniques in a physiological setting. The setting of the inflow cannula is substantially influenced by the fixation method of the sewing ring. Epicardial stitching showed the best results with stable cannula fixation, minimal gap around the cannula and no contact between the sutures and sewing ring with blood. The method of transmural stitching without back stitch showed the worst results by creating the biggest epithelial gap between inflow cannula and tissue as well as proving the biggest surface for blood contact between sewing ring and sutures. In general, both "sew-then-core" techniques resulted in a greater degree of apposition between the cuff and epicardial tissue. Within the study we revealed that the surgical fixation of the sewing ring has a significant impact on the inflow cannula stability, position, and tissue apposition in LVAD implantation surgery. Epicardial stitching of the sewing ring provides the best results in order to prevent suction events as well as thrombosis formation.

Chronic ventricular assist device support: surgical innovation.

PURPOSE OF REVIEW: Ventricular assist device (VAD) therapy is currently one of the fastest-developing fields in cardiac surgery. Consistently improved technology, research, and gain of clinical experience have established VADs as an important option for the treatment of congestive heart failure. During the past year, novel devices and less invasive surgical procedures have been revolutionizing this field. The purpose of this manuscript is to review these innovations with special emphasis on device-related surgery. RECENT FINDINGS: Device miniaturization has enabled less invasive VAD surgery, excluding the need for full sternotomy. Recent data show that intrahospital survival rates following less invasive VAD implantation are surpassing 90%. Secondly, two new devices, Heartmate 3 and MVAD, are being applied and tested for clinical application. In this context, the Heartmate 3 CE mark study recently concluded with excellent outcomes and without any pump thrombosis or device malfunctions. SUMMARY: The first clinical results of the newest generation of VADs are very promising compared with old-generation devices. Furthermore, less invasive surgery is becoming a standard for the implantation, exchange, or explantation of left VADs. The joint venture of improved technology and innovative surgical techniques will push this field forward to even better outcomes and reduced complication rates.