Mechanical Circulatory Support Systems Research Articles

Role of Lithotripsy for Small Calcified Iliacs in the Era of Big Devices.

In recent years, transcatheter aortic valve replacement (TAVR) and percutaneous mechanical circulatory support (MCS) systems have seen a widespread diffusion. These devices require the insertion of large femoral sheaths in a population of patients often presenting with calcific peripheral artery disease. Small and severely calcified iliac vessels are associated with increased risk of vascular complications or strategy changes such as the use of an alternative subclavian or transapical approach for TAVR or a conversion to surgery. Intravascular lithotripsy (IVL) technology applies mechanical pressure waves to modify vessel calcifications. It has been applied both in coronary and peripheral calcific disease with promising results. The use in vessel preparation before the insertion of large sheaths is an emerging application of this device. After case reports and presentations of isolated cases, two multicenter registries collected 42 and 12 patients treated with peripheral IVL before TAVR and MCS insertion. In most cases, the largest balloons were used in the iliac arteries with success achieved directly or using a separate insertion sheath in all cases. Low-pressure dilatation during energy delivery avoided dissections or vessel ruptures with no need of postprocedural stent implantation or emergency surgical repair. IVL can successfully modify the arterial compliance and facilitate transfemoral delivery of TAVR or MCS in patients with calcified iliofemoral vessels, reducing the need for alternative TAVR access routes and allowing to perform high-risk coronary procedures with adequate support.

Physical therapy in successful venoarterial extracorporeal membrane oxygenation bridge to orthotopic heart transplantation

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a temporary mechanical circulatory support system that may be used as a lifesaving therapy for patients in acute heart failure and as a bridge to definitive management. Physical therapy in these patients remains challenging, with limited protocols to guide practitioners. We describe a case of a 37-year-old gentleman who presented with familial cardiomyopathy and cardiogenic shock. Our patient underwent urgent peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) followed by successful heart transplantation. While on ECMO support he was enrolled in a physical therapy program that included the VitalGo Tilt Bed to improve lower body weight bearing while avoiding hip flexion and damage to the peripheral ECMO cannulae. The patient was discharged home expeditiously after heart transplant due to aggressive physical rehabilitation while on full VA-ECMO support. Early intensive physical rehabilitation is feasible and safe and may result in improved outcomes and expeditious discharge in VA ECMO patients. Protocol driven multidisciplinary physical therapy with a patient on femorally cannulated VA-ECMO retains the advantages of lower extremity peripheral cannulation while eliminating the risks of immobility. The new UNOS allocation system may result in a successful bridge to transplantation in patients on VA-ECMO due to the increased prioritization of this population to receive donor organs.

Gender aspects of incidence of antibody-mediated rejection and allograft vasculopathy events after heart transplantation

Abstract. Despite improvements in immunosuppressive therapy, antibody-mediated rejection (AMR) remains one of the most important risk factors for poor prognosis for survival of recipients, cardiac graft dysfunction, and cardiac allograft vasculopathy (CAV) after heart transplantation.Aim: to assess the incidence of case of antibodymediated rejection and cardiac allograft vasculopathy depending on the gender of the patients who underwent heart transplantation in our Center from January 2010 to December 2017.Methods. The median observation was 42 months. The study comprised 606 patients (84 [14%] women) who underwent heart transplantation in 2010 to 2017. We analyzed all the episodes of antibody-mediated rejection, which were diagnosed by the results of endomyocardial biopsies.Results. We comparing the total incidence of antibody-mediated rejection and we are found significant differences among men and women who underwent heart transplantation (p < 0.05), the survival rate during the first year after heart transplantation was 95 and 92%, respectively. The incidence of antibody-consistent rejection was significantly higher among women who had a history of pregnancy and/or use of mechanical circulatory support systems (UNOS status 1A) in the pre-transplantation history (p < 0.05), and we also found significant differences in the incidence of cardiac allograft vasculopathy in women diagnosed with AMR (p < 0.05). The survival rate among women within a year after the diagnosis of AMR is 83% compared to 96% of the recipients free from AMR.Conclusions. Women are at higher risk for AMR after heart transplantation and it increases their risk for cardiac allograft vasculopathy. Females recipients may more frequent myocardial control biopsies and a personalized approach in prescribing immunosuppressive therapy. Women-recipients of transplanted heart should undergo These measures will help to identify in time the development of antibodymediated rejection and reduce the incidence of cardiac allograft vasculopathy after heart transplant.

Invited Editorials Biomaterials science and engineering research in India Sunita P. Victor and Chandra P. Sharma State of the art-Artificial liver in China Yimin Zhang and Lanjuan Li Abstracts from the 15th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion.

Invited Editorials Biomaterials science and engineering research in India Sunita P. Victor and Chandra P. Sharma State of the art-Artificial liver in China Yimin Zhang and Lanjuan Li Abstracts from the 15th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion.

Device-induced platelet dysfunction in mechanically assisted circulation increases the risks of thrombosis and bleeding.

Thrombotic and bleeding complications are the major obstacles for expanding mechanical circulatory support (MCS) beyond the current use. While providing the needed hemodynamic support, those devices can induce damage to blood, particularly to platelets. In this study, we investigated device-induced alteration of three major platelet surface receptors, von Willebrand factor (VWF) and associated hemostatic functions relevant to thrombosis and bleeding. Fresh human whole blood was circulated in an extracorporeal circuit with a clinical rotary blood pump (CentriMag, Abbott, Chicago, IL, USA) under the clinically relevant operating condition for 4hours. Blood samples were examined every hour for glycoprotein (GP) IIb/IIIa activation and receptor loss of GPVI and GPIbα on the platelet surface with flow cytometry. Soluble P-selectin in hourly collected blood samples was measured by enzyme linked immunosorbent assay to characterize platelet activation. Adhesion of device-injured platelets to fibrinogen, collagen, and VWF was quantified with fluorescent microscopy. Device-induced damage to VWF was characterized with western blotting. The CentriMag blood pump induced progressive platelet activation with blood circulating time. Particularly, GPIIb/IIIa activation increased from 1.1% (Base) to 11% (4hours) and soluble P-selectin concentration increased from 14.1ng/mL (Base) to 26.5ng/mL (4hours). Those device-activated platelets exhibited increased adhesion capacity to fibrinogen. Concurrently, the CentriMag blood pump caused progressive platelet receptor loss (GPVI and GPIbα) with blood circulating time. Specifically, MFI of the GPVI and GPIbα receptors decreased by 17.2% and 16.1% for the 4-hours sample compared to the baseline samples, respectively. The device-injured platelets exhibited reduced adhesion capacities to collagen and VWF. The high molecular weight multimers (HMWM) of VWF in the blood disappeared within the first hour of the circulation. Thereafter the multimeric patterns of VWF were stable. The change in the VWF multimeric pattern was different from the progressive structural and functional changes of platelets with the circulation time. This study suggested that the CentriMag blood pump could induce two opposite effects on platelets and associated hemostatic functions under a clinically relevant operating condition. The device-altered hemostatic function may contribute to thrombosis and bleeding simultaneously as occurring in patients supported by a rotary blood pump. Device-induced damage of platelets may be an important cause for bleeding in patients supported with rotary blood pump MCS systems relative to device-induced loss of HMWM-VWF.

Transition from Short-Term to Durable Mechanical Circulatory Support Systems. Outcome and Patient Selection. On Behalf of ECMO-VAD Study Group

Purpose The implantation of durable ventricular assist devices (VAD) in patients on veno-arterial membrane oxygenation (VA-ECMO) is controversial. Available studies in this field are limited to anecdotal case reports. In this study, data of ten high volume VA-ECMO/VAD centers are collected and analysed. Methods Following approval from corresponding ethic committees, data of patients undergoing durable mechanical circulatory support implantations at ten institutions between 01.2010 - 07.2018 were reviewed. Inclusion criteria are patients with prior VA-ECMO support. Several parameters including patient´s characteristics, results of blood gas analysis, blood chemistry, and catecholamine doses prior to the assist device surgery are collected and analysed. The primary endopint was survival or cardiac transplantation at one year. Results A total of 494 patients met the inclusion criteria. The average age was 53 ± 12 yrs. The majority of the patients (82%) were male and 33% of the patients had cardiopulmonary resuscitaion prior to the VA-ECMO implantation. The mean VA-ECMO support duration prior to durable device implantation was 7 ± 8 days. Up to 34 % of the patients were on renal dialysis. Cardiopulmonary bypass was used in 63% of the patients at the time of durable device surgery. Less invasive VAD implantation was performed in 19% of the patients. Type of implanted pump included HeartWare HVAD (70%), HeartMate II (17%), HeartMate III (8%), CardioWest TAH (3.6%) and other pumps in (1.4%). The 30 day, 1 year and 2 year survival was 75 and 50% and 40% respectively. Postoperative complications included right heart failure requiring right VAD in 41% of patients, bleeding requiring resternotomy in 38%, respiratory failure in 65%, renal failure in 68% and hepatic failure in 35% of the patients. Stroke rate was 21%. Heart transplantation was performed in 33% of the patients. Conclusion In this largest ever reported series of durable assist device patients with prior VA-ECMO support, higher rate of postoperative right ventricular failure and bleeding /end organ function complications are observed compared to elective VAD implantations. Nevertheless, considering preoperative characteristics of these patients, acceptable outcome of 50% 1 year success was achieved.

Acquired von Willebrand Syndrome Associated with Cardiovascular Diseases.

The blood glycoprotein von Willebrand factor (VWF) plays an important role in hemostasis and thrombosis. VWF is produced and secreted as large multimers by endothelial cells and megakaryocytes. It is then cleaved in a sheer-stress dependent manner by a specific protease, ADAMTS13, into multimers consisting of 2–80 subunits. Among VWF multimers, high molecular weight (HMW) multimers play important roles in platelet aggregation. Therefore, their loss induces a hemostatic disorder known as von Willebrand disease (VWD) type 2A. Various cardiovascular diseases, such as aortic stenosis, hypertrophic obstructive cardiomyopathy (HOCM), and several congenital structural diseases, as well as mechanical circulatory support systems, generate excessive high shear stress in the bloodstream. These cause excessive cleavage of VWF multimers resulting in a loss of HMW multimers, known as acquired von Willebrand syndrome (AVWS), a hemostatic disorder similar to VWD type 2A. Bleeding often occurs in the gastrointestinal tract since a fragile angiodysplasia develops associated with these diseases. Radical treatment for AVWS is to remove the pathological high shear causing AVWS.

Artificial Organs 2018: A Year in Review.

In this Editor's Review,articles published in 2018 are organized by category and summarized. We provide a briefreflection of the research and progress in artificial organs intended to advance and better human life while providing insight for continued application of these technologies and methods. Artificial Organs continues in the original mission of its founders "to foster communications in the field of artificial organs on an international level." Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery,and Regeneration from all over the world. Peer-reviewed special issues this year included contributions from the 13thInternational Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion edited by Dr. Akif Undar, and the 25th Congress of the International Society for Mechanical Circulatory Support edited by Dr. Marvin Slepian. Additionally, many editorials highlighted the worldwide survival differences in hemodialysis and perspectives on mechanical circulatory support and stem cell therapies for cardiac support. We take this time also to express our gratitudeto our authors foroffering their work to this journal. Weoffer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide meaningful suggestions to the author's work whether eventually accepted or rejected. Without these excellent and dedicated reviewers the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, John Wiley & Sons for their expert attention and support in the production andmarketing of Artificial Organs. We look forward to reporting further advances in the coming years.

Large-bore Vascular Closure: New Devices and Techniques.

Endovascular aneurysm repair, transcatheter aortic valve implantation and percutaneous mechanical circulatory support systems have become valuable alternatives to conventional surgery and even preferred strategies for a wide array of clinical entities. Their adoption in everyday practice is growing. These procedures require large-bore access into the femoral artery. Their use is thus associated with clinically significant vascular bleeding complications. Meticulous access site management is crucial for safe implementation of large-bore technologies and includes accurate puncture technique and reliable percutaneous closure devices. This article reviews different strategies for obtaining femoral access and contemporary percutaneous closure technologies.

Inter-hospital transfer of extracorporeal membrane oxygenation-assisted patients: the hub and spoke network.

The treatment of cardiogenic shock (CS) in peripheral hospitals may be challenging when acute mechanical circulatory support (MCS) is not available. Tertiary care centers may provide mobile extracorporeal membrane oxygenation (ECMO) teams to support the treatment of CS-patients externally. We retrospectively analyzed our single-center experience with a mobile ECMO team focussing on decision-making and survival data of CS-patients retrieved by ECMO support from peripheral hospitals to our tertiary care center between January 2012 and October 2018. A total number of 134 CS-patients have been retrieved by ECMO support to our center within the observation period. Forty-three (32%) died on the acute MCS device, while 59 (44%) patients could be weaned from the acute MCS. Twenty-nine (22%) were bridged to implantation of a durable MCS system and 6 were finally transplanted. The overall 1-year survival was 33%. Interestingly, advanced patient age did not significantly affect survival. Acute MCS for CS may be provided by experienced mobile teams allowing for retrieval of patients from peripheral hospitals to tertiary care centers. Relatively low survival rates oppose intensive material and human resources. It is therefore mandatory to constantly refine logistics and selection criteria.

Mechanical shear stress and leukocyte phenotype and function: Implications for ventricular assist device development and use.

Heart failure remains a disease of ever increasing prevalence in the modern world. Patients with end-stage heart failure are being referred increasingly for mechanical circulatory support. Mechanical circulatory support can assist patients who are ineligible for transplant and stabilise eligible patients prior to transplantation. It is also used during cardiopulmonary bypass surgery to maintain circulation while operating on the heart. While mechanical circulatory support can stabilise heart failure and improve quality of life, complications such as infection and thrombosis remain a common risk. Leukocytes can contribute to both of these complications. Contact with foreign surfaces and the introduction of artificial mechanical shear stress can lead to the activation of leukocytes, reduced functionality and the release of pro-inflammatory and pro-thrombogenic microparticles. Assessing the impact of mechanical trauma to leukocytes is largely overlooked in comparison to red blood cells and platelets. This review provides an overview of the available literature on the effects of mechanical circulatory support systems on leukocyte phenotype and function. One purpose of this review is to emphasise the importance of studying mechanical trauma to leukocytes to better understand the occurrence of adverse events during mechanical circulatory support.

Abstract 17377: The Effect of Mechanical Circulatory Support on HLA Antibodies and Antibody-Mediated Rejection in Cardiac Allografts

Introduction: Due to the shortage of donor organs, mechanical circulatory support systems (MCS) are now widely used as a treatment option to bridge the failing heart to transplant. It has been observed that MCS patients show a higher frequency of antibody-mediated rejection (AMR) episodes. The latter is thought to represent an immune reaction directed against the device in terms of allosensitation. Hypothesis: Capillary C4d and/or C3d depositions are required to diagnose AMR in cardiac allografts. We aimed to analyze the effect of MCS on pre- and post-HTx HLA antibodies and their correlation to cardiac AMR with due regards to capillary C3d and C4d depositions. Methods: We evaluated all consecutive right ventricular protocol endomyocardial biopsies (EMBs) of cardiac allografts which fulfilled the ISHLT- criteria (254 patients) during two consecutive calendar years. With regards to pre- transplant MCS treatment patients were divided into two groups (MCS group n=82 patients, non MCS group n= 138 patients). Conventional histology and immunohistochemical stains were used on formalin-fixed paraffin-embedded tissue sections (FFPE) to evaluate the EMBs regarding AMR (complements C3d and C4d). Permutation test (x 2 ) was performed to analyze the relationship between C4d and C3d and pre-and post-transplant HLA-antibodies, measured using Luminex assay, in all patient subgroups. Cochran-Mantel-Haenzsel was performed to assure the significance of the difference of interactions in both tables. Results: The statistical analysis showed in the MCS group a highly significant positive correlation between C3d and Pre-Tx-HLA (p=0.012, Pre-Tx-HLA Class I and II p= 0.042, respectively vs p=0.884 and p=0.349 in non-MCS group), which levelled out following HTx (p= 0.867 and 0.697 for HLA Class I and II, vs p=0.212 and p=0.682 in non-MCS group, respectively). Statistical significance was not reached between C4d and pre-or post Tx HLA-antibodies in any group (p=0.349 vs. p=0.694 for entire study population). Conclusions: We demonstrated that C3d correlates solely in the MCS group with pre-Tx HLA antibodies and could therefore add to the diagnosis of AMR if the pre-transplant treatment is being considered in the diagnostic setting.

Outcomes of the Fourteenth International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion.

Outcomes of the Fourteenth International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion.

Nursing Challenges in Interactions With Patients Receiving Mechanical Circulatory and Respiratory Support.

Mechanical circulatory and respiratory support (MCRS) systems provide short- to long-term life support for patients with severe cardiac or respiratory failure. Whereas the challenges of patients with these lifesaving systems are well understood, the challenges faced by nurses of patients receiving MCRS remain relatively unidentified. In this study, we investigated the challenges and experiences of MCRS nurses, with the aim of informing the design of future interventions. A qualitative approach was taken to develop an in-depth understanding of the emotional issues nurses experience in their daily interactions with patients. Nine MCRS nurses ranging in clinical experience were recruited from Australian hospitals. Participants were divided into 3 focus groups, with design prompts being used in the focus groups to facilitate discussion. Data from these focus groups were analyzed through a thematic analysis protocol. The nurses' accounts were clustered around 2 themes, including (1) patient connection and (2) compassion vitality and fatigue. Each theme elicits a conflicting compromise that MCRS nurses face daily. The challenges of nurses who support patients with MCRS are complex, multifaceted, emotionally stimulating, and exhausting. We therefore contributes a set of design criteria to support such nurses, setting a direction for future research.

Experimental Study on Net Flow Rate Generation Inside Closed Loop Mechanical Circulatory System Using Impedance Pump

This present study focused on the performance of net flow rate inside closed loop mechanical circulatory system with single and double pinching impedance pumps which generates a unidirectional flow of fluid around closed loop of soft viscoelastic tubing. The experimental setup consisted of viscoelastic tubing connected between two ends of rigid tube which was compressed rhythmically or squeezed asymmetrically at various frequencies by motorized pinching. Hence, net flow of fluid around the tubing can occur without valves. Experiment was done on two different fluid, namely Newtonian and Non-Newtonian. Result showed that the flow rate inside closed loop system for non-Newtonian fluid and Newtonian fluid were in good agreement with each other. Single pinching showed a lower flow rate compared to double pinching at higher frequency. The results could be used as a model for a new Mechanical Circulatory Support System used by cardiac patients. Factors influencing the performance of valveless impedance pump was also explained.

10-YEAR HEART TRANSPLANTATION EXPERIENCE IN NOVOSIBIRSK

Aim:to show the analysis of 10-year heart transplantation experience, the main complications and problems of the heart transplantation evaluation. Materials and methods.66 orthotopic heart transplantations were performed in patients with terminal chronic heart failure in our clinic since 2008. The heart failure causes were dilated cardiomyopathy in 46 cases (70%), postinfarction cardiosclerosis in 20 cases (30%). The recipients were 59 men (89%) and 7 women (11%), the average age was 46 ± 10 years. All patients had a severe left heart dilatation and critical left ventricular systolic dysfunction (left ventricular EDV 283 ± 58 ml, left ventricular ejection fraction 17 ± 5%, cardiac index 1.5 ± 0.3 l/min/m2). In some recipients, heart transplantation is performed in the second stage after preliminary implantation of mechanical circulatory support systems (LVAD, BVAD). The fi rst heart transplantations were performed using the biatrial technique (8 cases (12%)), the others were performed using the bicaval technique (58 cases (88%)). After the operation, patients received a three-component immunosuppressive therapy: the inhibitors of calcineurin, mycophenolate and corticosteroids.Results.54 patients (82%) were discharged from the clinic after heart transplantation. The hospital mortality was 12 recipients (18%). The mortality in the long-term period was 10 recipients (15%). The hospital mortality cases were acute graft dysfunction in 5 cases (42%), infectious-septic complications in 4 cases (33%), massive intraoperative bleeding in 2 cases (17%), and total thrombosis of pulmonary artery in 1 case (8%). The death causes in the long-term period were acute transplant rejection in 4 cases (40%), coronary artery disease of the transplanted heart in 3 cases (30%), Kaposi’s sarcoma in 1 case (10%), lung cancer in 1 case (10%), and viral pneumonia in 1 case (10%).Conclusion.Over a 10-year period, we have gained a lot of experience in heart transplantation; the procedures complications have been studied; the stages of preservation, harvesting and transportation of the donor heart, operative technique and postoperative treatment of patients have been improved to avoid complications in the early and long-term postoperative period.

Mechanical circulatory support in terminal heart failure

After exhaustion of all conservative measures in the treatment of acute and chronic heart insufficiency, there is the possibility to temporarily or permanently support or replace the pump performance of the heart by mechanical circulatory support (MCS) systems. Presentation of the most important cardiac support systems for intensive care medicine, their indications and important risk factors. Critical review of device manufacturer's specifications, current research and expert opinions. The spectrum of available MCS procedures include mechanical chest compression devices, catheter-based micropumps and complete artificial hearts. Device selection depends on the severity of heart failure (monoventricular or biventricular pump failure), the expected duration of treatment and the degree of lung function impairment. The decision between minimally invasive and open surgical procedures depends on the options established at the specific healthcare institution and whether the heart function is to be temporarily or permanently replaced. Compliance with the anticoagulation regimens defined by the manufacturer is especially important as they differ vastly between devices and are critical to avoid bleeding or thromboembolic complications. Due to the increasing number of patients on long-term mechanical circulatory support, the chances are that physicians in the initial emergency admission are unfamiliar with these devices but need to operate them in emergency cases. Therefore, knowledge of these procedures and their complications becomes increasingly important.

Percutaneous biventricular Impella support in therapy-refractory cardiogenic shock

IntroductionPercutaneous mechanical circulatory support systems have increasingly been adopted as a bail out strategy in patients with cardiogenic shock. Since studies showed mostly mixed results, however, the use of support systems remains a case by case decision. CaseHere, we report on a case of therapy-refractory cardiogenic shock due to acute myocardial infarction treated with percutaneous right and left ventricular assist devices (Impella RP and CP). ConclusionDue to myocardial stunning, even patients with fulminant cardiogenic shock have the potential for full recovery. In the present case, we demonstrate the feasibility of biventricular Impella support in therapy-refractory cardiogenic shock facilitating bridge to recovery.

Artificial Organs 2017: A Year in Review.

In this Editor's Review, articles published in 2017 are organized by category and summarized. We provide a brief reflection of the research and progress in artificial organs intended to advance and better human life while providing insight for continued application of these technologies and methods. Artificial Organs continues in the original mission of its founders "to foster communications in the field of artificial organs on an international level." Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. Peer-reviewed Special Issues this year included contributions from the 12th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion edited by Dr. Akif Undar, Artificial Oxygen Carriers edited by Drs. Akira Kawaguchi and Jan Simoni, the 24th Congress of the International Society for Mechanical Circulatory Support edited by Dr. Toru Masuzawa, Challenges in the Field of Biomedical Devices: A Multidisciplinary Perspective edited by Dr. Vincenzo Piemonte and colleagues and Functional Electrical Stimulation edited by Dr. Winfried Mayr and colleagues. We take this time also to express our gratitude to our authors for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide meaningful suggestions to the author's work whether eventually accepted or rejected. Without these excellent and dedicated reviewers the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, John Wiley & Sons for their expert attention and support in the production and marketing of Artificial Organs. We look forward to reporting further advances in the coming years.

A hemostatic disorder caused by high shear stress: acquired von Willebrand syndrome

The von Willebrand factors (VWFs) play critical role in hemostasis and thrombosis formation. VWFs are produced in and secreted as large multimers from endothelial cells, and shear stress-dependently cleaved into 2-80 multimers by their specific protease, ADATS13. Because high molecular weight VWFs play important roles in platelet aggregation, the loss of high molecular weight VWFs caused by pathological high-shear stress induces a hemostatic disorder known as acquired von Willebrand syndrome (AVWS) type IIA. The most well-known cause of this loss is aortic stenosis, which is accompanied by gastrointestinal bleeding most often as a result of angiodysplasia; this comprises a condition known as Heyde's syndrome. Additionally, various cardiovascular diseases that generate excessive high-shear stress in the blood stream, such as hypertrophic obstructive cardiomyopathy (HOCM), mitral regurgitation, pulmonary hypertension, and some congenital heart diseases, and mechanical circulatory support systems, such as left ventricular assist device (LVAD), cause AVWS.