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Objective Genetically engineered pigs are thought to be an alternative organ source for patients in end-stage heart failure unable to receive a timely allograft. However, cardiac xenografts exhibit growth and diastolic heart failure within 1 month after transplantation. Grafts function for up to 6 months, but only after administration of temsirolimus and afterload-reducing agents to reduce this growth. In this study we investigated the growth and hemodynamics of growth hormone receptor (GHR) knockout xenografts, without the use of adjuncts to prevent intrinsic graft growth after transplantation. Methods Genetically engineered pig hearts were transplanted orthotopically into weight-matched baboons between 15 and 30 kg, using continuous perfusion preservation before implantation (n = 5). Xenografts included knockout of carbohydrate antigens and knockin of human transgenes for thromboregulation, complement regulation, and inflammation reduction (grafts with intact growth hormone, n = 2). Three grafts contained the additional knockout of GHR (GHR knockout grafts; n = 3). Transthoracic echocardiograms were obtained twice monthly and comprehensively analyzed by a blinded cardiologist. Hemodynamics were measured longitudinally after transplantation. Results All xenografts demonstrated life-supporting function after transplantation. There was no difference in intrinsic growth, measured using septal and posterior wall thickness and left ventricular mass, on transthoracic echocardiogram out to 1 month in either GHR knockout or GHR intact grafts. However, hypertrophy of the septal and posterior wall was markedly elevated by 2 months post transplantation. There was minimal hypertrophy out to 6 months in GHR knockout grafts. Physiologic mismatch was present in all grafts after transplantation, which is largely independent of growth. Conclusions Xenografts with GHR knockout show reduced post-transplantation xenograft growth using echocardiography >6 months after transplantation, without the need for other adjuncts.

BACKGROUND: Urgent surgery requiring heparin exposure during cardiopulmonary bypass can be challenging in patients with acute heparin-induced thrombocytopenia (HIT). The use of treatments such as therapeutic plasma exchange (TPE) to remove HIT antibodies and intravenous immunoglobulin (IVIg) to antagonize HIT antibody-mediated platelet activation are increasingly reported in patients who undergo cardiac surgery. The optimal treatment approach to mitigate the risks of heparin administration in this situation is not known. KEY CLINICAL QUESTION: Can TPE coupled to IVIg allow for safe heparin exposure in patients with HIT? CLINICAL APPROACH: TPE and IVIg were used to enable heparin exposure for surgical placement of a left ventricular assist device in a patient with HIT. Serial patient samples were tested in antigen-based and functional HIT assays. CONCLUSION: Dissociation between antigen-based (enzyme-linked immunosorbent assay) and functional (serotonin release assay) testing was noted, and TPE coupled to IVIg was associated with an excellent clinical response.

Extracorporeal life support (ECLS) was first implemented as an extension of cardiopulmonary bypass technology. The early use of ECLS in patients with acute respiratory distress syndrome (ARDS) was discouraging, likely due to limitations of technology and understanding of the disease process. However, over the last decade, there has been a rapid expansion in ECLS use. This ”rebirth” in 2009 was largely driven by the need for ECLS during the Influenza A subtype H1N1 pandemic and the results of the conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) trial showing improved outcomes in patients with ARDS on ECLS compared to traditional management. Along with the increase in overall use of ECLS, there has been an increase in the number of patients with lung failure who are on long-term support, either awaiting lung recovery or transplantation. Many of these patients are awake, participating in physical rehabilitation, and even ambulating while supported with ECLS. Given the recent advances in patient care, and improvements in ECLS technology, the movement towards home for stable patients supported with ECLS may be on the horizon. Patients supported with ventricular assist devices (VAD) underwent a similar transition towards home in the 1990s, before which they were hospital bound. The road to an ambulatory home wearable lung will likely mirror that pathway. This review will give a brief overview of the transition of VAD patients out of the hospital, the history of ECLS, the current state of ECLS for lung failure, new and upcoming ECLS technology, and hurdles on the road home for ECLS patients.

Objectives The COMMENCE trial was conducted to evaluate the safety and effectiveness of an aortic bioprosthesis with novel RESILIA tissue (Edwards Lifesciences, Irvine, Calif). Reports of early noncalcific valve failure resulting from thrombosis or leaflet tears in other valves warrant careful evaluation of early valve performance. Methods Patients underwent clinically indicated surgical aortic valve replacement with the Edwards Pericardial Aortic Bioprosthesis, Model 11000A (Edwards Lifesciences) in a prospective, multinational, multicenter (n = 27), single-arm, Food and Drug Administration Investigational Device Exemption trial. Events were adjudicated by an independent clinical events committee; echocardiograms were analyzed by an independent core laboratory. Results Between January 2013 and March 2016, 689 patients received the study valve. Mean age was 67.0 ± 11.6 years. Mean Society of Thoracic Surgeons predicted risk of mortality was 2.0% ± 1.8%. Follow-up duration was 3.7 ± 1.2 years, with a total of 2533 patient years of follow-up and a median follow-up of 4 years. Early all-cause mortality was 1.2%, thromboembolism 2.3%, all bleeding 1.0%, and major paravalvular leak 0.1%. One- and 4-year actuarial freedom from all-cause mortality was 97.7% (95% confidence interval, 96.5%-98.8%) and 91.9% (95% confidence interval, 89.7%-94.1%), respectively. At 4 years, New York Heart Association functional class improved compared with baseline in 63.0%, effective orifice area was 1.5 ± 0.5 cm2, and mean gradient was 11.0 ± 5.6 mm Hg. Freedom from moderate or greater transvalvular insufficiency was 99.7%. There were no events of structural valve deterioration. Conclusions Safety and hemodynamic performance of this aortic bioprosthesis with RESILIA tissue at 4 years are favorable. This novel tissue does not appear to result in unexpected early thrombosis events or noncalcific structural valve deterioration.

Left ventricular assist devices (LVADs) have been increasingly used as a therapy for patients with end-stage heart failure. However, a growing number of clinical observations have shown that LVADs are associated with thromboembolic events, which are potentially related to the changes in intraventricular flow. Particularly, the flow fields around the inflow cannula (IC) of the LVAD. In this study, a fluid structure interaction (FSI) simulation was conducted to evaluate the hemodynamics of a patient specific left ventricle (LV) with varying LVAD IC orientations. The LV model was obtained from computed tomography scans and modeled to have contraction and relaxation during cardiac cycles following available experimental data of LV volume changes. The LV of the patient was assumed to have an end systolic volume of 223.7 mL and a stroke volume of 46.4 mL. Four different IC positions were considered: towards the (1) septum; (2) aortic valve (AV); (3) mitral valve (MV) and (4) inferior wall (IW). The potential thrombus growth around the IC was assumed to be caused by blood stagnation regions with low velocity (

Objective Leukocytes play an important role in the body's immune system. The aim of this study was to assess alterations in neutrophil phenotype and function in pump-assisted circulation in-vitro. Methods Human blood was circulated for four hours in three circulatory flow loops with a CentriMag blood pump operated at a flow of 4.5 L/min at three rotational speeds (2100, 2800, and 4000 rpm), against three pressure heads (75 mmHg, 150 mmHg, and 350 mmHg), respectively. Blood samples were collected hourly for analyses of neutrophil activation state (Mac-1, CD62L, CD162), neutrophil reactive oxygen species (ROS) production, apoptosis, and neutrophil phagocytosis. Results Activated neutrophils indicated by both Mac-1 expression and decreased surface expression of CD62L and CD162 receptors increased with time in three loops. The highest level of neutrophil activation was observed in the loop with the highest rotational speed. Platelet-neutrophil aggregates (PNAs) progressively increased in two loops with lower rotational speeds. PNAs peaked at one hour after circulation and decreased subsequently in the loop with the highest rotational speed. Neutrophil ROS production dramatically increased at one hour after circulation and decreased subsequently in all three loops with similar levels and trends. Apoptotic neutrophils increased with time in all three loops. Neutrophil phagocytosis capacity in three loops initially elevated at one hour after circulation and decreased subsequently. Apoptosis and altered phagocytosis were dependent on rotational speed. Conclusions Our study revealed that the pump-assisted circulation induced neutrophil activation, apoptosis, and functional impairment. The alterations were strongly associated with pump operating condition and duration.

Blood pumps have been increasingly used in mechanically assisted circulation for ventricular assistance and extracorporeal membrane oxygenation support or during cardiopulmonary bypass for cardiac surgery. However, there have always been common complications such as thrombosis, hemolysis, bleeding, and infection associated with current blood pumps in patients. The development of more biocompatible blood pumps still prevails during the past decades. As one of those newly developed pumps, the Breethe pump is a novel extracorporeal centrifugal blood pump with a hybrid magnetic and mechanical bearing with attempt to reduce device-induced blood trauma. To characterize the hydrodynamic and hemolytic performances of this novel pump and demonstrate its superior biocompatibility, we use a combined computational and experimental approach to compare the Breethe pump with the CentriMag and Rotaflow pumps in terms of flow features and hemolysis under an operating condition relevant to ECMO support (flow: 5 L/min, pressure head: ~350 mmHg). The computational results showed that the Breethe pump has a smaller area-averaged wall shear stress (WSS), a smaller volume with a scalar shear stress (SSS) level greater than 100 Pa and a lower device-generated hemolysis index compared to the CentriMag and Rotaflow pumps. The comparison of the calculated residence times among the three pumps indicated that the Breethe pump might have better washout. The experimental data from the in vitro hemolysis testing demonstrated that the Breethe pump has the lowest normalized hemolysis index (NIH) than the CentriMag and Rotaflow pumps. It can be concluded based on both the computational and experimental data that the Breethe pump is a viable pump for clinical use and it has better biocompatibility compared to the clinically accepted pumps.

We have been testing genetically engineered (GE) pig hearts and optimizing immunosuppression (IS) in non-human primates (NHPs) since 2005. We demonstrate how we translated this preclinical investigation into a US Food and Drug Administration (FDA)-approved clinical cardiac xenotransplantation. First, genetically engineered (GE) pig hearts were transplanted into the abdomen of NHP along with IS, which included anti-CD20 and anti-CD40-based co-stimulation blockade antibodies. We reported 945 days of survival of three gene GE pig hearts in NHPs. Building on this proof-of-concept, we tested 3-10 gene-modified GE pig hearts (in order to improve the immunocompatibility of the xenograft further) in a life-supporting orthotopic model, but had limited success due to perioperative cardiac xenograft dysfunction (PCXD). With novel non-ischemic continuous perfusion preservation (NICP), using the XVIVO Heart solution (XHS), life-supporting survival was extended to 9 months. We approached the FDA under an application for "Expanded Access" (EA), to transplant a GE pig heart in a patient with end-stage non-ischemic cardiomyopathy. He was without other therapeutic options and dependent on VA-ECMO. A team of FDA reviewers reviewed our preclinical research experience and data and allowed us to proceed. This clinical cardiac xenotransplantation was performed, and the patient survived for 60 days, demonstrating the translational preclinical investigation of cardiac xenotransplantation from bench to bedside. The ultimate etiology of graft failure is currently a topic of investigation and lessons learned will progress the field forward.

A summary of the scientific rationale of the advancements that led to the first genetically modified pig-to-human cardiac xenotransplantation is lacking in a complex and rapidly evolving field. Here, we aim to aid the general readership in the understanding of the gradual progression of cardiac (xeno)transplantation research, the immunobiology of cardiac xenotransplantation (including the latest immunosuppression, cardiac preservation and genetic engineering required for successful transplantation) and the regulatory landscape related to the clinical application of cardiac xenotransplantation for people with end-stage heart failure. Finally, we provide an overview of the outcomes and lessons learned from the first genetically modified pig-to-human cardiac heart xenotransplantation.

Non-physiological shear stress (NPSS) and thrombin have two distinct mechanisms for activating platelets. NPSS in mechanically assisted circulation (MAC) devices can cause platelet dysfunction, e.g., by shedding its key receptors. In addition, patients with heart failure have increased levels of thrombin generation, which may further affect the NPSS-induced platelet dysfunction, resulting in device-associated complications. This study aimed to assess the combined effect of NPSS and thrombin in platelet activation, expression of adhesion receptors on the platelet surface, and alterations of platelet aggregation.Fresh human blood from healthy donors was divided into two groups; one group was treated by adding 0.01 U/mL thrombin, and another group not treated with thrombin served as a control comparison. They were then pumped through a novel blood shearing device which produces similar shear stress conditions to those in the MAC devices. Three levels of NPSS (i.e., 75, 125, and 175 Pa) with a 1.0 s exposure time were selected for the shearing conditions. Expression of platelet activation markers (PAC-1, activated GPIIb/IIIa and CD62P, platelet surface P-selectin) were investigated along with the shedding of platelet receptors (GPIb, GPIIb/IIIa, and GPVI), generation of platelet microparticles, and Phosphatidylserine (PS)-positive platelets detected by flow cytometry. Platelet aggregation (induced by collagen/ristocetin) was measured by Lumi-aggregometry.Platelet receptors were shed after exposure to NPSS showing a positive correlation with the level of shear stress. The generation of platelet microparticles and PS-positive platelets also increased with greater NPSS. Elevated NPSS decreased the platelet aggregation capacity. Platelet activation level increased with greater NPSS. Being treated by thrombin can further exacerbate these characteristics under same level of NPSS, except that platelet activation level drastically dropped after the exposure to 175 Pa NPSS in the thrombin-treated blood.After being treated by thrombin, platelets became more susceptible to NPSS, resulting in more receptor shedding, platelet microparticles, and PS-positive platelets, thus limiting platelet aggregation capacity after exposure to NPSS. Platelet activation, in terms of PAC-1 and P-selectin, is an interim status competing between the expression and shedding of these makers/receptors. When platelets have reached a saturation level of activation, exposure to excessive NPSS can potentially impair activation.

This paper proposes a biomechanical platelet model with an intracellular prestressed assumption. The platelet structure is composed of a membrane cortex and a marginal band (MB). The membrane cortex is assumed in a spherical shape in its initial state and modeled using spring-network elements widely used for the similar membrane structure of red blood cells. The MB is modeled as one solid torus, which employs the hyperelastic material model, and is confined inside the cortex through a contact model. In the initial equilibrium state, the platelet has a stable, flat, and discoid shape. Upon activation, the possible mechanism of the unbinding rate of crosslink between the microtubules (MTs) is assumed to break the homogeneous stiffness of the MB, which causes the platelet to have a disc-to-sphere morphological transition. The numerical results and the experimental images of the MBs show good agreement. The proposed model provides a novelty in relating the mechanical property changes of the MB to the platelet morphological changes upon activation, thus, can provide a possible engineering tool to reveal the intriguing behavior of platelet upon activation.

A 57-year-old man with nonischemic cardiomyopathy who was dependent on venoarterial extracorporeal membrane oxygenation (ECMO) and was not a candidate for standard therapeutics, including a traditional allograft, received a heart from a genetically modified pig source animal that had 10 individual gene edits. Immunosuppression was based on CD40 blockade. The patient was weaned from ECMO, and the xenograft functioned normally without apparent rejection. Sudden diastolic thickening and failure of the xenograft occurred on day 49 after transplantation, and life support was withdrawn on day 60. On autopsy, the xenograft was found to be edematous, having nearly doubled in weight. Histologic examination revealed scattered myocyte necrosis, interstitial edema, and red-cell extravasation, without evidence of microvascular thrombosis - findings that were not consistent with typical rejection. Studies are under way to identify the mechanisms responsible for these changes. (Funded by the University of Maryland Medical Center and School of Medicine.).

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest has improved mortality in post-cardiac surgery patients; however, loss of neurologic function remains one of the main and devastating complications. We reviewed our experience with ECPR and investigated the effect of cannulation strategy on neurologic outcome in adult patients who experienced cardiac arrest following cardiac surgery that was managed with ECPR. Methods: Patients were categorized by central versus percutaneous peripheral VA-extracorporeal membrane oxygenation (ECMO) cannulation strategy. We reviewed patient records and evaluated in-hospital mortality, cause of death, and neurologic status 72 hours after cannulation. Results: From January 2010 to September 2019, 44 patients underwent post-cardiac surgery ECPR for cardiac arrest. Twenty-six patients received central cannulation; 18 patients received peripheral cannulation. Mean post-operative day of the cardiac arrest was 3 and 9 days (p = 0.006), and mean time between initiation of CPR and ECMO was 40 ± 24 and 28 ± 22 minutes for central and peripheral cannulation, respectively. After 72 hours of VA-ECMO support, 30% of centrally cannulated patients versus 72% of peripherally cannulated patients attained cerebral performance status 1–2 (p = 0.01). Anoxic brain injury was the cause of death in 26.9% of centrally cannulated and 11.1% of peripherally cannulated patients. Survival to discharge was 31% and 39% for central and peripheral cannulation, respectively. Conclusions: Peripheral VA-ECMO allows for continuous CPR and systemic perfusion while obtaining vascular access. Compared to central cannulation, a peripheral cannulation strategy is associated with improved neurologic outcomes and decreased likelihood of anoxic brain death.

Background This study compares outcomes of conventional and less-invasive (LI) approaches for aortic valve replacement (AVR) using The Society of Thoracic Surgeons database. Methods Between 2011 and 2017, we identified 122,474 patients undergoing isolated primary AVR. Patients were categorized into 3 groups: (1) full sternotomy (FS) (n = 98,549; 78%), (2) partial sternotomy (PS) (n = 17,306; 15%), and (3) right thoracotomy (RT) (n = 6619; 7%). Results The rate of LI-AVR increased from 17% in 2011 to 23% in 2016 (P Conclusions Less-invasive AVR is associated with an operative mortality and postoperative stroke rate similar to that of FS. Less-invasive AVRs should serve as a benchmark for comparison between transcatheter aortic valve replacement and surgical AVR in low-risk patients.

Objective We have observed that minimally invasive left ventricular assist device (LVAD) insertion leads to more facile re-entry and easier cardiac transplantation. We hypothesize minimally invasive LVAD implantation results in improved outcomes at the time of subsequent heart transplant. Methods All adults undergoing cardiac transplantation between October 2015 and March 2019 at our institution were retrospectively reviewed. Those bridged to transplantation with a HeartWare HVAD were identified and divided into 2 cohorts based upon the surgical approach: those who underwent HVAD placement by conventional sternotomy versus minimally invasive insertion via lateral thoracotomy and hemisternotomy (LTHS). Patient demographics, as well as perioperative transplant outcomes, including survival, length of stay (LOS), blood utilization, ischemic time, bypass time, and postoperative extracorporeal membrane oxygenation (ECMO) were compared between cohorts. Results Forty-two patients were bridged to heart transplant with a HVAD implanted via either sternotomy ( n = 22) or LTHS technique ( n = 20). Demographics were similar between groups. There was 1 predischarge death in the sternotomy group and none in the LTHS group. Body surface area, cardiopulmonary bypass time, ischemic time, ECMO utilization, and reoperation for bleeding were similar. Red blood cell units transfused were significantly lower in the LTHS cohort (3.0 [1.0-5.0] vs 6.0 [2.5-10.0] P = 0.046). The LTHS cohort had a significantly shorter hospital LOS (12.0 [11.0-28.0] vs 22.5 [15.7-41.7] P = 0.022) with a trend toward shorter intensive care unit LOS (6.0 [5.0-10.5] vs 11.0 [6.0-21.5] days P = 0.057). Conclusions Minimally invasive HVAD implantation improves outcomes at subsequent heart transplantation, resulting in shorter LOS and less red cell transfusion. Larger multi-institutional studies are necessary to validate these findings.

We report orthotopic (life-supporting) survival of genetically engineered porcine cardiac xenografts (with six gene modifications) for almost 9 months in baboon recipients. This work builds on our previously reported heterotopic cardiac xenograft (three gene modifications) survival up to 945 days with an anti-CD40 monoclonal antibody-based immunosuppression. In this current study, life-supporting xenografts containing multiple human complement regulatory, thromboregulatory, and anti-inflammatory proteins, in addition to growth hormone receptor knockout (KO) and carbohydrate antigen KOs, were transplanted in the baboons. Selective "multi-gene" xenografts demonstrate survival greater than 8 months without the requirement of adjunctive medications and without evidence of abnormal xenograft thickness or rejection. These data demonstrate that selective "multi-gene" modifications improve cardiac xenograft survival significantly and may be foundational for paving the way to bridge transplantation in humans.

Ex vivo lung perfusion (EVLP) allows for a reassessment of lung grafts initially deemed unsuitable for transplantation, increasing the available donor pool; however, this requires a pre- and post-EVLP period of cold ischemic time (CIT). Paucity of data exists on how the sequence of cold normothermic-cold preservations affect outcomes.A total of 110 patients were retrospectively analyzed. Duration of 3 preservation phases was measured: cold pre-EVLP, EVLP, and cold post-EVLP. The donor and recipient clinical data were collected. Primary graft dysfunction (PGD) and survival were monitored. Risk of mortality or PGD was calculated using Cox proportional hazards and logistic regression models to adjust for baseline characteristics.Using the highest quartile, patients were stratified into extended vs non-extended pre-EVLP (264 vs ≥264 minutes) and post-EVLP (287 vs ≥287 minutes) CIT. The rates of 1-year mortality (8.4% vs 29.6%, p = 0.013), PGD 2-3 (20.5% vs 52%, p = 0.002), and PGD 3 (8.4% vs 29.6%, p = 0.005) at 72 hours were increased in the extended post-EVLP CIT group. After adjusting for baseline risk factors, the extended group remained an independent predictor of PGD ≥2 (odd ratio: 6.18, 95% CI: 1.88-20.3, p = 0.003) and PGD 3 (odd ratio: 20.4, 95% CI: 2.56-161.9, p = 0.004) at 72 hours and 1-year mortality (hazard ratio: 17.9, 95% CI: 3.36-95.3, p = 0.001). Cold pre-EVLP was not a significant predictor of primary outcomes.Extended cold post-EVLP preservation is associated with a risk for PGD and 1-year mortality. Pre-EVLP CIT does not increase mortality or high-grade PGD. These findings from a multicenter trial should caution on the implementation of extended cold preservation after EVLP.

Resectional and artificial cordal repair techniques are effective strategies for degenerative mitral valve (MV) repair. However, resectional repair requires a tailored approach using various techniques, whereas cordal repair offers a simpler, easily reproducible repair. The approach described in this study approach has evolved from resectional to cordal over time, and outcomes are compared between the eras.Clinical and echocardiographic outcomes of all patients undergoing MV repair for degenerative mitral regurgitation (MR) from January 2004 to September 2017 were reviewed. Patients were stratified by era: from January 2004 to June 2011 (era 1; n = 405), resectional techniques were used in 62% and artificial cordal techniques were used in 38%. From July 2011 to September 2017 (era 2; n = 438), artificial cordal repair was used in 98% of patients. The primary outcome was repair failure, defined as greater than moderate MR or MV reoperation.Of 847 patients with degenerative MR, successful repair was achieved in 843 patients (99.5% repair rate). Leaflet prolapse was posterior in 66%, anterior in 8%, and bileaflet in 26%. Cardiopulmonary bypass time and cross-clamp times were shorter in era 2 (CPB: 109 [IQR, 92-128] minutes vs 97 [IQR, 76-121] minutes; P.001; cross-clamp: 88 [IQR, 73-106] minutes vs. 79 [IQR, 61-99] minutes; P.001). Predismissal echocardiography demonstrated no MR or trace MR in 95%, mild MR in 4.7%, and moderate MR in 0.3% of patients. Operative mortality was similar in the eras (0.5% vs 0.5%; P.999). The rates of 5-year freedom from repair failure (95.1% vs 95.5%; P = .707), stroke (96.8% vs 95.3%; P = .538), and endocarditis (99.3% vs 99.7%; P = .604) were similar between the eras.Artificial cordal repair for all patients with degenerative MR simplifies MV repair and yields equivalent, excellent outcomes compared with a tailored resectional approach.

Introduction: Extracorporeal membrane oxygenation circuit performance can be compromised by oxygenator thrombosis. Stagnant blood flow in the oxygenator can increase the risk of thrombus formation. To minimize thrombogenic potential, computational fluid dynamics is frequently applied for identification of stagnant flow conditions. We investigate the use of computed tomography angiography to identify flow patterns associated with thrombus formation. Methods: A computed tomography angiography was performed on a Quadrox D oxygenator, and video densitometric parameters associated with flow stagnation were measured from the acquired videos. Computational fluid dynamics analysis of the same oxygenator was performed to establish computational fluid dynamics–based flow characteristics. Forty-one Quadrox D oxygenators were sectioned following completion of clinical use. Section images were analyzed with software to determine oxygenator clot burden. Linear regression was used to correlate clot burden to computed tomography angiography and computational fluid dynamics–based flow characteristics. Results: Clot burden from the explanted oxygenators demonstrated a well-defined pattern, with the largest clot burden at the corner opposite the blood inlet and outlet. The regression model predicted clot burden by region of interest as a function of time to first opacification on computed tomography angiography (R2 = 0.55). The explanted oxygenator clot burden map agreed well with the computed tomography angiography predicted clot burden map. The computational fluid dynamics parameter of residence time, when summed in the Z-direction, was partially predictive of clot burden (R2 = 0.35). Conclusion: In the studied oxygenator, clot burden follows a pattern consistent with clinical observations. Computed tomography angiography–based flow analysis provides a useful adjunct to computational fluid dynamics–based flow analysis in understanding oxygenator thrombus formation.

Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as a promising initial support strategy for acute massive pulmonary embolism. However, it remains unclear which patients will ultimately require surgical pulmonary embolectomy (SPE) vs anticoagulation alone. Methods All consecutive patients (2015-2018) with confirmed massive PE, placed on VA-ECMO utilizing a protocolized approach, were reviewed. Per protocol, patients were supported for 3 to 5 days before reevaluation of right ventricular (RV) function via echocardiography. If RV function recovered, VA-ECMO was discontinued with no further intervention (no-SPE group). In patients with persistent RV dysfunction, SPE was performed. Results Forty-five patients were identified, and 41 patients were treated per protocol. Seventy-three percent responded to anticoagulation alone, and 27% required SPE. Factors associated with SPE rather than decannulation with anticoagulation alone included prolonged shortness of breath, elevated N-terminal prohormone of brain natriuretic peptide, enlarged pulmonary artery diameter, and history of venous thromboembolism. A predictive algorithm was developed with a negative predictive value of 97% and a specificity of 97% for a low-risk score, and a positive predictive value of 100% and sensitivity of 67% for a high-risk score. Overall, 90-day survival was 97% in the no-SPE group and 100% in the SPE group. Conclusions In this cohort, greater than 70% of patients who presented with massive PE and supported with VA-ECMO ultimately recovered with anticoagulation alone. Specific risk factors, likely related to thrombus chronicity, may be associated with lack of RV recovery, and can be utilized for consideration of early surgical intervention to minimize VA-ECMO duration.

Background Despite improved survival and morbidity after durable left ventricular assist device (dLVAD), outcomes for cardiogenic shock patients are suboptimal. Temporary mechanical circulatory support (tMCS) can permit optimization before dLVAD. Excellent outcomes have been observed using minimally-invasive dLVAD implantation. However, some feel tMCS contraindicates this approach. To evaluate whether left thoracotomy/hemisternotomy (LTHS) dLVAD placement is safe in this setting, we compared patients who did and did not require tMCS. Methods Outcomes for patients receiving dLVADs via LTHS were compared among those bridged with extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), or no tMCS. We evaluated demographics, comorbidities, laboratory and hemodynamic data, and intraoperative and postoperative outcomes. Results Eighty-three patients underwent LTHS dLVAD placement. Fifty did not require tMCS, while 22 (26%) required IABP, and 11 (13%) ECMO. Non-tMCS patients were primarily Intermacs 3 (56%), while IABP recipients were mainly Intermacs 2 (45%). All patients with ECMO were Intermacs 1. Patients with tMCS had worse end-organ function. Operative outcomes were similar except more concomitant procedures and red-cell transfusions in patients with ECMO. Intensive care unit and hospital length of stay and inotrope duration were also similar. There were no differences in bleeding, stroke, and infection rates. Three- and 12-month survival were: no tMCS: 94%, 86%; IABP: 100%, 88%; and ECMO: 81%, 81% (P = .45). Conclusions Patients with cardiogenic shock can safely undergo LTHS dLVAD implantation after stabilization with ECMO or IABP. Outcomes and complications in these patients were comparable to a less severely ill cohort without tMCS.

Patients supported with venovenous extracorporeal membrane oxygenation are at risk for intra-abdominal hypertension and abdominal compartment syndrome. Flow through the return cannula may be compromised in these patients, resulting in inadequate support and end-organ malperfusion. Early decompressive laparotomy can mitigate these complications and potentially improve outcomes. Here we review a series of nine patients undergoing early decompressive laparotomy for abdominal compartment syndrome at a single institution and propose an algorithmic approach to the management of these patients.

In order to explore the role of a disintegrin and metalloproteinase (ADAM) proteolysis and direct mechanical damage in non-physiologic shear stress (NPSS)-caused platelet receptor shedding, the healthy donor blood treated with/without ADAM inhibitor was exposed to NPSS (150 Pa). The expression of the platelet surface receptors glycoprotein (GP) Ibα and glycoprotein (GP) VI (GPVI) in NPSS-damaged blood was quantified with flow cytometry. The impact of ADAM inhibition on adhesion of NPSS-damaged platelets on von Willibrand factor (VWF) and collagen was explored with fluorescence microscopy. The impact of ADAM inhibition on ristocetin- and collagen-caused aggregation of NPSS-damaged platelets was examined by aggregometry. The results showed that ADAM inhibition could lessen the NPSS-induced loss of platelet surface receptor GPIbα (12%) and GPVI (9%), moderately preserve adhesion of platelets on VWF (7.4%) and collagen (8.4%), and partially restore the aggregation of NPSS-sheared platelets induced by ristocetin (18.6 AU*min) and collagen (48.2 AU*min). These results indicated that ADAM proteolysis played a role in NPSS-induced receptor shedding. However, the ADAM inhibition couldn't completely suppress the NPSS-caused loss of the platelet surface receptors (GPIbα and GPVI), only partially prevented the NPSS-induced reduction of platelet adhesion to VWF and collagen, and the agonist (ristocetin and collagen)-caused platelet aggregation. These results suggested that the direct mechanical damage is partially responsible for NPSS-induced receptor shedding in addition to the ADAM proteolysis. In conclusion, NPSS relevant to blood contacting medical devices can induce ADAM proteolysis and direct mechanical damage on the platelet receptor GPIbα and GPVI, leading to comprised hemostasis.

Objective Despite improvement in outcomes after left ventricular assist device (LVAD) implantation over the past 2 decades, high-risk recipients continue to have a prohibitive rate of morbidity and mortality. We hypothesized that a less invasive approach to LVAD implantation would be associated with improved survival compared to a conventional approach in this high-risk cohort. Methods All consecutive LVAD recipients (2013 to 2017) that underwent centrifugal LVAD implantation were retrospectively reviewed. Patients were classified as high-risk if INTERMACS 1 or required temporary VAD/venoarterial extracorporeal membrane oxygenation prior to durable VAD implantation. Patients were stratified into 3 groups: left thoracotomy with hemi-sternotomy (LTHS) high-risk, conventional sternotomy (CS) high-risk, and non-high-risk. The primary outcome was 1-year survival. Results A total of 57 patients (LTHS high-risk: 11, CS high-risk: 12, non-high-risk: 34) were identified. Preoperative right ventricular failure scores, HeartMate-II mortality scores, and end-organ dysfunction were similar between the 2 high-risk groups. While operative time was similar between the 3 groups, cardiopulmonary bypass time was significantly shorter in the LTHS high-risk group compared to other groups. There was a trend toward decreased intensive care unit length of stay and ventilator time in LTHS high-risk compared to CS high-risk patients. Moreover, between these 2 groups, there was a significant decrease in temporary right VAD support (50% vs 0%, P = 0.014), and 1-year survival was significantly higher in the LTHS group (42% vs 91%, P = 0.025). Conclusions Less invasive LVAD implantation appears to be associated with improved survival compared to conventional LVAD implantation in high-risk patients.

OBJECTIVE: The roles of the large membrane surface of the oxygenator and the high mechanical shear stress (HMSS) of the pump in the ECMO circuit were examined under a pediatric support setting. METHODS: A clinical centrifugal pump and a pediatric oxygenator were used to construct the ECMO circuit. An identical circuit without the oxygenator was constructed for comparison. Fresh human blood was circulated in the two circuits for 4 hours under the identical pump speed and flow. Blood samples were collected hourly for blood damage assessment, including platelet activation, generation of platelet-derived microparticles (PDMP), losses of key platelet hemostasis receptors (glycoprotein (GP) Ibα (GPIbα) and GPVI) and high molecular weight multimers (HMWM) of von Willebrand factor (VWF) and plasma free hemoglobin (PFH). Platelet adhesion on fibrinogen, VWF and collagen was further examined. RESULTS: The levels of platelet activation and generation of PDMP and PFH exhibited an increasing trend with circulation time while the expression levels of GPIbα and GPVI receptors on the platelet surface decreased. Correspondingly, the platelets in the blood samples exhibited increased adhesion capacity to fibrinogen and decreased adhesion capacities on VWF and collagen with circulation time. Loss of HMWM of VWF occurred in both circuits. No statistically significant differences were found in all the measured parameters for blood damage and platelet adhesion function between the two circuits. CONCLUSIONS: The results indicate that HMSS from the pump played a dominant role in blood damage associated with ECMO and the impact of the large surface of the oxygenator on blood damage was insignificant.

Left ventricular assist devices are routinely used to treat patients with advanced heart failure as a bridge to transplant or a destination therapy. However, non-physiological shear stress generated by left ventricular assist devices damages blood cells. The continued development of novel left ventricular assist devices is essential to improve the left ventricular assist device therapy for heart failure patients. The CH-VAD is a new maglev centrifugal left ventricular assist device. In this study, the CH-VAD pump was numerically analyzed and compared with the HVAD and HeartMate II pumps under two clinically relevant conditions (flow: 4.5 L/min, pressure head: normal ~80 and hypertension ~120 mmHg). The velocity and shear stress fields, washout, and hemolysis index of the three pumps were assessed with computational fluid dynamics analysis. Under the same condition, the CH-VAD hemolysis index was two times lower than the HVAD and HeartMate II pumps; the CH-VAD had the least percentage volume with shear stress larger than 100 Pa (i.e. normal condition: 0.4% vs HVAD 1.0%, and HeartMate II 2.9%). Under the normal condition, more than 98% was washed out of the three pumps within 0.4 s. The washout times were slightly shorter under the hypertension condition for the three pumps. No regions inside the CH-VAD or HVAD had extremely long residential time, while areas near the straightener of the HeartMate II pump had long residential time (>4 s) indicating elevated risks of thrombosis. The computational fluid dynamics results suggested that the CH-VAD pump has a better hemolytic biocompatibility than the HVAD and HeartMate II pumps under the normal and hypertension conditions.

Extracorporeal membrane oxygenation (ECMO) has become a mainstay of therapy for patients suffering from severe respiratory failure. Ambulatory ECMO systems aim to provide long-term out-of-hospital respiratory support. As a patient’s activity level changes, the required level of ECMO support varies with oxygen consumption and metabolic fluctuations. To compensate for such changes, an Auto-Regulatory ECMO system (AR-ECMO) has been developed and its performance was evaluated as a proof-of-concept in an acute ovine model. The AR-ECMO system consists of a regular ECMO circuit and an electromechanical control system. A custom fuzzy-logic control algorithm was implemented to adjust the blood flow and sweep gas flow of the ECMO circuit to meet the varying respiratory demand by utilizing two noninvasive sensors for venous oxyhemoglobin saturation and the oxygenator exhaust gas CO2 concentration. Disturbance responses of the AR-ECMO to induced acute respiratory distress were assessed for six hours in four juvenile sheep cannulated with a veno-pulmonary artery ECMO configuration, including acute ventilator shutoff, ventilator step-change (off-on-off), and forced desaturation. All sheep survived for the study duration. The AR-ECMO system was able to respond and maintain stable hemodynamics and physiological blood gas contents (SpO(2) = 96.3 % ± 4.29, pH = 7.44 ± 0.09, pCO(2) = 38.9 ± 9.9 mmHg, and pO(2) =237.9 ± 123.6 mmHg) during simulated respiratory distress. Acceptable correlation between oxygenator exhaust gas CO(2) and oxygenator outlet pCO(2) were observed (R(2)= 0.84). In summary, the AR-ECMO system successfully maintained physiologic control of peripheral oxygenation and carbon dioxide over the study period, utilizing only measurements taken directly from the ECMO circuit. The range of system response necessitates an adaptable system in the setting of variable metabolic demands. The ability of this system to respond to significant disturbances in ventilator support is encouraging. Future work to evaluate our AR-ECMO system in long-term, awake animal studies is necessary for further refinement.

Background: Structural valve deterioration (SVD) is the Achilles heel of bioprosthetic valves used for aortic valve replacement (AVR). SVD has been traditionally defined based upon the requirement ...