Hemocompatibility and biophysical interface of left ventricular assist devices and total artificial hearts.

ABSTRACT: Over the past 2 decades, there has been a significant increase in the utilization of long-term mechanical circulatory support (MCS) for the treatment of cardiac failure. Left ventricular assist devices (LVADs) and total artificial hearts (TAHs) have been developed in parallel to serve as bridge-to-transplant and destination therapy solutions. Despite the distinct hemodynamic characteristics introduced by LVADs and TAHs, a comparative evaluation of these devices regarding potential complications in supported patients, has not been undertaken. Such a study could provide valuable insights into the complications associated with these devices. Although MCS has shown substantial clinical benefits, significant complications related to hemocompatibility persist, including thrombosis, recurrent bleeding, and cerebrovascular accidents. This review focuses on the current understanding of hemostasis, specifically thrombotic and bleeding complications, and explores the influence of different shear stress regimens in long-term MCS. Furthermore, the role of endothelial cells in protecting against hemocompatibility-related complications of MCS is discussed. We also compared the diverse mechanisms contributing to the occurrence of hemocompatibility-related complications in currently used LVADs and TAHs. By applying the existing knowledge, we present, for the first time, a comprehensive comparison between long-term MCS options.

RBCs Regulate Platelet Function and Hemostasis under Shear Conditions through Biophysical and Biochemical Means.

Red blood cells (RBCs) have been hypothesized to support hemostasis by facilitating platelet margination and releasing platelet-activating factors such as adenosine diphosphate (ADP). Significant knowledge gaps remain regarding how RBCs influence platelet function, especially in (patho)physiologically relevant hemodynamic conditions. Here we present results showing how RBCs affect platelet function and hemostasis in conditions of anemia, thrombocytopenia, and pancytopenia, and how the biochemical and biophysical properties of RBCs regulate platelet function at the blood-vessel wall interface and in the fluid phase under flow conditions. We found that RBCs promoted platelet deposition to collagen under flow conditions in moderate (50  103/L) but not severe (10  103/L) thrombocytopenia in vitro. Reduction in hematocrit by 45% led to increased bleeding in mice with hemolytic anemia. In contrast, bleeding diathesis was observed in mice with a 90% but not with a 60% reduction in platelet counts. RBC transfusion improved hemostasis by enhancing fibrin clot formation at the site of vascular injury in mice with severe pancytopenia induced by total body irradiation. Altering membrane deformability changed the ability of RBCs to promote platelet aggregation. RBC-derived ADP contributed to platelet activation and aggregation in vitro under pathologically high shear stresses, as observed in patients supported by left ventricular assist devices. These findings demonstrate that RBCs support platelet function and hemostasis through multiple mechanisms, both at the blood-vessel wall interface and in the fluidic phase of circulation.

Coronary flow capacity and survival prediction after revascularization: physiological basis and clinical implications.

BACKGROUND AND AIMS: Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization. METHODS: Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0. RESULTS: Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025). CONCLUSIONS: Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization.

STAR procedure becomes SAFER: First-in-man case series of a new antegrade dissection re-entry technique.

INTRODUCTION: Antegrade dissection and re-entry (ADR) is an integral part of the hybrid algorithm, which has allowed for improved outcomes in chronic total occlusion (CTO) coronary intervention (PCI). METHODS: A new ADR method, Subintimal Antegrade FEnestration and Re-entry (SAFER), is described. The results of a first-in-man series are presented. RESULTS: SAFER was performed on seven consecutive patients with angiographic and clinical success in all patients. CONCLUSIONS: This first-in-man study has shown that the SAFER technique is feasible and effective with the possibility of improving the antegrade PCI CTO success rate.

The use of veno-arterial extracorporeal membrane oxygenation in the octogenarian population: A single-center experience.

INTRODUCTION: Advanced age is a known risk factor for poor outcomes after veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for cardiac support. The use of ECMO support in patients over the age of 80 is controversial, and sometimes its use is contraindicated. We aimed to assess the use of ECMO in octogenarian patients to determine survival and complication rates. METHODS: A single-center, retrospective analysis was completed at a large, urban academic medical center. Patients requiring V-A ECMO support between December of 2012 and November of 2019 were included as long as the patient was at least 80 years of age at the time of cannulation. Post cardiotomy shock patients were excluded. RESULTS: A total of 46 patients met eligibility criteria; all received V-A ECMO support. Overall, the majority of patients (71.7%; 33/46) survived to decannulation, and 43.5% (20/46) survived to discharge. Patients who were previously rescued from percutaneous interventions tend to have a better survival than other patients (p = .06). The most common complications were renal and hemorrhagic. CONCLUSIONS: We demonstrated that advanced age alone should not disqualify patients from cannulating and supporting with V-A ECMO.

Traumatic respiratory failure and veno-venous extracorporeal membrane oxygenation support.

BACKGROUND: Respiratory failure (RF) is a common cause of death and morbid complication in trauma patients. Extracorporeal membrane oxygenation (ECMO) is increasingly used in adults with RF refractory to invasive mechanical ventilation. However, use of ECMO remains limited for this patient population as they often have contraindications for anticoagulation. STUDY DESIGN: Medical records were retroactively searched for all adult patients who were admitted to the trauma service and received veno-venous ECMO (VV ECMO) support between June 2015 and August 2018. Survival to discharge and ECMO-related complications were collected and analyzed. RESULTS: Fifteen patients from a large Level I trauma center met the criteria. The median PaO2/FiO2 ratio was 53.0 (IQR, 27.0-76.0), median injury severity score was 34.0 (IQR, 27.0-43.0), and the median duration of ECMO support was 11 days (IQR, 7.5-20.0). For this cohort, the survival-to-discharge rate was 87% (13/15). The incidence of neurologic complications was 13%, and deep vein thrombosis was reported in two cases (13%). CONCLUSIONS: Survival rates of trauma patients in this study are equivalent to, or may exceed, those of non-trauma patients who receive ECMO support for other types of RF. With the employment of a multidisciplinary team assessment and proper patient selection, early cannulation, traumatic RF may be safely supported with VV ECMO in experienced centers.

Acquired von Willebrand syndrome associated with left ventricular assist device.

Left ventricular assist devices (LVAD) provide cardiac support for patients with end-stage heart disease as either bridge or destination therapy, and have significantly improved the survival of these patients. Whereas earlier models were designed to mimic the human heart by producing a pulsatile flow in parallel with the patient's heart, newer devices, which are smaller and more durable, provide continuous blood flow along an axial path using an internal rotor in the blood. However, device-related hemostatic complications remain common and have negatively affected patients' recovery and quality of life. In most patients, the von Willebrand factor (VWF) rapidly loses large multimers and binds poorly to platelets and subendothelial collagen upon LVAD implantation, leading to the term acquired von Willebrand syndrome (AVWS). These changes in VWF structure and adhesive activity recover quickly upon LVAD explantation and are not observed in patients with heart transplant. The VWF defects are believed to be caused by excessive cleavage of large VWF multimers by the metalloprotease ADAMTS-13 in an LVAD-driven circulation. However, evidence that this mechanism could be the primary cause for the loss of large VWF multimers and LVAD-associated bleeding remains circumstantial. This review discusses changes in VWF reactivity found in patients on LVAD support. It specifically focuses on impacts of LVAD-related mechanical stress on VWF structural stability and adhesive reactivity in exploring multiple causes of AVWS and LVAD-associated hemostatic complications.

Transcatheter aortic valve implantation with a Sapien 3 Commander 20 mm valves in patients with degenerated 19 mm bioprosthetic aortic valve.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) in patients with degenerated bioprosthetic aortic valve has been successfully performed as an alternative to surgery. We describe our initial experience of valve-in-valve TAVI in five patients, using new generation Edwards Sapien 3 transcatheter heart valves implanted into degenerated 19 mm bioprosthetic valves. 20-mm Edwards S3 valves were offered for compassionate use. All patients had significant aortic valve stenosis. METHODS AND RESULTS: The main vascular access was achieved and pre-closed with two Proglide closure devices in one patient and Prostar closure devices in four patients. For each TAVI procedure an Edwards 14 French sheath was inserted without complication and sutured in place. The Sapien 3 Commander delivery system was inserted and the valve was aligned in the descending aorta. The 20-mm Sapien 3 valve was deployed with slow continuous inflation during rapid right ventricular pacing. The cranial edge of the Edwards S3 valve was aligned with the cranial radiopaque markers of bioprosthesis to minimize paravalvular leak. Post-deployment angiography, transesophageal echocardiography and aortogram confirmed absence of mild aortic insufficiency and no increase in trans-aortic gradient when compared to a naïve 19 mm bioprosthetic valve. CONCLUSION: Valve-in-valve TAVI with the Edwards S3 transcatheter heart valve for degenerative bioprosthetic aortic valves is technically feasible. The proper position of the stented valve minimizes the risk for post-procedure paravalvular insufficiency and provides good transaortic pressure gradient. © 2016 Wiley Periodicals, Inc.

Percutaneous coronary intervention with the TandemHeart™ percutaneous left ventricular assist device support: Six years of experience and outcomes.

OBJECTIVES: Our study was designed to evaluate the outcomes of TandemHeart™ assistance during percutaneous coronary intervention, specifically in relationship to pre-procedural clinical and hemodynamic risk factors in patients ineligible for surgical revascularization. BACKGROUND: We have used the TandemHeart™ percutaneous left ventricular assist device during percutaneous coronary intervention (PCI) in patients for whom conventional PCI and aorto-coronary bypass would pose substantial risk owing to comorbidities and/or clinical presentations. METHODS: We retrospectively analyzed data from 626 consecutive PCIs at the Texas Heart Institute from 2005 to 2011. Among these, 74 interventions were performed with TandemHeart™ support. Mortality and morbidity were analyzed in relationship to presentation status (elective, urgent, emergent, or emergent salvage), and then we recorded outcomes and survival rates over the course of six years. RESULTS: At 30 days after PCI, survival rates were 94%, 88%, 79%, and 55% in the elective, urgent, emergent, and emergent salvage groups, respectively. Survival rates at one year were at 75% in the elective, 64% in the urgent, 52% in the emergent, and 45% in the emergent salvage groups. Survival rates at 6 years were 68% in the elective, 53% in the urgent, 31% in the emergent, and 41% in the emergent salvage groups, respectively. In elective and urgent groups, successful weaning from mechanical support was possible in all patients. In the emergent and emergent salvage groups, successful weaning from mechanical support was possible in 84% and 55% of patients, respectively. CONCLUSIONS: TandemHeart™ assisted PCI is a viable option for revascularization in cases of profound cardiogenic shock or extremely risky intervention due to complex anatomy. © 2015 Wiley Periodicals, Inc.

Use of Percutaneous Left Ventricular Assist Device Before Durable Device Implantation in Patients With Cardiac Cachexia: Case Series.

Frailty and malnutrition in patients with heart failure are barriers to durable left ventricular assist device (D-LVAD) support and heart transplantation. Moreover, cachexia in patients with advanced heart failure carries a high mortality risk. There are no guidelines for these patients other than increased caloric intake and rehabilitation. Patients suffering from cardiac cachexia and heart failure may benefit from temporary, percutaneous assist device support to improve the underlying heart disease and reverse the catabolic state. We retrospectively reviewed patients from January 2017 to January 2022. All patients who received Impella support (5.0 or 5.5, Abiomed) before D-LVAD implantation were screened. Those who met the criteria for cardiac cachexia were included. Patient demographics, nutritional and biochemical markers, and survival data were collected. A total of 14 patients were included. The majority of patients were male (85.7%) with ischemic cardiomyopathy (64.3%). Caloric intake, physical strength, and ambulation improved. Prealbumin levels improved from a median of 13.7-18.0 mg/dl ( p < 0.006) while on Impella 5.0 or 5.5 support. All patients survived to discharge and the 6 month follow-up. In conclusion, use of the Impella device improves cardiogenic shock symptoms and, consequently, may improve cachexia status prior to D-LVAD implantation.

Does the Type of Chronic Heart Failure Impact In-Hospital Outcomes for Aortic Valve Replacement Procedures?

BACKGROUND: This study assessed in-hospital outcomes of patients with chronic systolic, diastolic, or mixed heart failure (HF) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). METHODS: The Nationwide Inpatient Sample database was used to identify patients with aortic stenosis and chronic HF who underwent TAVR or SAVR between 2012 and 2015. Propensity score matching and multivariate logistic regression were used to determine outcome risk. RESULTS: A cohort of 9,879 patients with systolic (27.2%), diastolic (52.2%), and mixed (20.6%) chronic HF were included. No statistically significant differences in hospital mortality were noted. Overall, patients with diastolic HF had the shortest hospital stays and lowest costs. Compared with patients with diastolic HF, the risk of acute myocardial infarction (TAVR odds ratio [OR], 1.95; 95% CI, 1.20-3.19; P = .008; SAVR OR, 1.38; 95% CI, 0.98-1.95; P = .067) and cardiogenic shock (TAVR OR, 2.15; 95% CI, 1.43-3.23; P < .001; SAVR OR, 1.89; 95% CI, 1.42-2.53; P ≤ .001) was higher in patients with systolic HF, whereas the risk of permanent pacemaker implantation (TAVR OR, 0.58; 95% CI, 0.45-0.76; P < .001; SAVR OR, 0.58; 95% CI, 0.40-0.84; P = .004) was lower following aortic valve procedures. In TAVR, the risk of acute deep vein thrombosis and kidney injury was higher, although not statistically significant, in patients with systolic HF than in those with diastolic HF. CONCLUSION: These outcomes suggest that chronic HF types do not incur statistically significant hospital mortality risk in patients undergoing TAVR or SAVR.

Use of the SAPIEN 3 Transcatheter Heart Valve in High-Risk Scenarios.

The transcatheter aortic valve replacement procedure is used in patients with aortic stenosis. Transcatheter aortic valve replacement devices are quite versatile; thus, they are increasingly being used for nonaortic applications, such as tricuspid valve-in-valve implantation. This case series describes a transcatheter aortic valve replacement procedure in 4 patients with anatomic challenges (eg, aortic tortuosity, high valvular calcium burden, highly calcified bicuspid valve, low coronary artery takeoff, left main coronary artery occlusion, and large aortic annulus) and a fifth patient who had a failed tricuspid bioprosthesis and underwent a tricuspid valve-in-valve implantation with the Edwards SAPIEN 3 transcatheter heart valve (Edwards Lifesciences). All procedures required adjustments to the standard protocol, and each procedure was successful. The critical, technical adjustments in the deployment technique and preprocedural planning of the procedures are detailed to provide a road map for other cardiologists who encounter similar challenges.

Pre- and post-operative mechanical circulatory support in surgical repair of post-acute myocardial infarction mechanical complications.

The outcomes of patients with acute myocardial infarctions (AMI) have significantly improved with advances in early reperfusion strategies; however, patients with massive infarcts or those who do not receive timely revascularization may develop mechanical complications of AMI. The most common mechanical complications are ventricular septal rupture (VSR), acute mitral regurgitation (MR) due to papillary muscle rupture, and free-wall rupture. Each complication is associated with a high risk of morbidity and mortality, and requires a multidisciplinary approach for prompt diagnosis and hemodynamic stabilization. Surgery is the mainstay of therapy but is associated with poor outcomes if performed too early during the treatment course for VSR or if performed too late with MR and free wall rupture. Optimal timing for surgery in combination with temporary circulatory support may be a feasible strategy for better results.

Surgically Implanted Impella Device for Patients on Impella CP Support Experiencing Refractory Hemolysis.

The Impella CP (Abiomed Inc., Danvers, MA) is widely used in cardiac catheterization laboratories for patients presenting with cardiogenic shock, but it is also known to cause significant hemolysis. The risk of hemolysis can be reduced by properly positioning the device, ensuring an adequate volume status, and using full anticoagulation strategies; however, in some cases hemolysis persists. We present a case series of eight patients that were diagnosed with cardiogenic shock, underwent Impella CP placement, and then suffered from refractory hemolysis which was treated by upgrading the Impella device to the 5.0 or 5.5 version. Fifty percent (4/8) of the patients in this series were already receiving continuous renal replacement therapy, and the levels of plasma free hemoglobin (pFHb) and lactate dehydrogenase continued to increase after the implantation of the Impella CP. The median time between Impella CP placement and the diagnosis of refractory hemolysis was 16.5 hours (interquartile range [IQR], 8.0-26.0). The median time between the diagnosis of hemolysis to Impella upgrade was 6.0 hours (IQR, 4.0-7.0). A total of 87.5% (7/8) of patients experienced a drop in pFHb to below 40 mg/dl at 72 hours post-Impella upgrade, and they were discharged without any further need of dialysis. One patient expired due to irreversible multiple organ failure. We propose that early identification of hemolysis by close monitoring of pFHb and upgrading to the Impella 5.5 reduces hemolysis, prevents further kidney damage, and significantly improves clinical outcomes.

Hyperadhesive von Willebrand Factor Promotes Extracellular Vesicle-Induced Angiogenesis: Implication for LVAD-Induced Bleeding.

Bleeding associated with left ventricular assist device (LVAD) implantation has been attributed to the loss of large von Willebrand factor (VWF) multimers to excessive cleavage by ADAMTS-13, but this mechanism is not fully supported by the current evidence. We analyzed VWF reactivity in longitudinal samples from LVAD patients and studied normal VWF and platelets exposed to high shear stress to show that VWF became hyperadhesive in LVAD patients to induce platelet microvesiculation. Platelet microvesicles activated endothelial cells, induced vascular permeability, and promoted angiogenesis in a VWF-dependent manner. Our findings suggest that LVAD-driven high shear stress primarily activates VWF, rather than inducing cleavage in the majority of patients.

Notch1 regulates the fate of cardiac progenitor cells.

The Notch receptor mediates cell fate decision in multiple organs. In the current work we tested the hypothesis that Nkx2.5 is a target gene of Notch1 and raised the possibility that Notch1 regulates myocyte commitment in the adult heart. Cardiac progenitor cells (CPCs) in the niches express Notch1 receptor, and the supporting cells exhibit the Notch ligand Jagged1. The nuclear translocation of Notch1 intracellular domain (N1ICD) up-regulates Nkx2.5 in CPCs and promotes the formation of cycling myocytes in vitro. N1ICD and RBP-Jk form a protein complex, which in turn binds to the Nkx2.5 promoter initiating transcription and myocyte differentiation. In contrast, transcription factors of vascular cells are down-regulated by Jagged1 activation of the Notch1 pathway. Importantly, inhibition of Notch1 in infarcted mice impairs the commitment of resident CPCs to the myocyte lineage opposing cardiomyogenesis. These observations indicate that Notch1 favors the early specification of CPCs to the myocyte phenotype but maintains the newly formed cells in a highly proliferative state. Dividing Nkx2.5-positive myocytes correspond to transit amplifying cells, which condition the replicative capacity of the heart. In conclusion, Notch1 may have critical implications in the control of heart homeostasis and its adaptation to pathologic states.

Percutaneous Thrombus Removal in COVID-19-Infected Patient with Pulmonary Embolism.

We present a case describing the use of the AngioVac system (AngioDynamics, Inc.) and SENTINEL™ cerebral protection system (SCPS; Boston Scientific) in a patient with COVID-19 who initially presented with a large deep-vein thrombosis of the left lower extremity, complicated by a pulmonary embolism. Although he initially improved with systemic alteplase, he later developed a second large clot diagnosed in transit in the right atrium. Within 12 hours from initial thrombolysis, this large clot wedged across an incidental patent foramen ovale (PFO), the atrial septum, and the cavotricuspid annulus. We emergently performed a percutaneous clot extraction with preemptive placement of the SCPS in anticipation of cardioembolic phenomenon. A large (> 10 cm) clot was extracted without complication, and the patient was discharged home. The combined use of SCPS and AngioVac in this case suggests a potential role for percutaneous treatment of severe and consequential thromboembolic disease, especially in patients with a PFO, and may be considered as an alternative and less-invasive option in patients with COVID-19. While cerebral embolic protection devices are approved for and widely used in transcatheter aortic valve replacement procedures, there is a theoretical benefit for use in percutaneous thrombolectomies as well.

Regional, Artery-Specific Thresholds of Quantitative Myocardial Perfusion by PET Associated with Reduced Myocardial Infarction and Death After Revascularization in Stable Coronary Artery Disease.

Because randomized coronary revascularization trials in stable coronary artery disease (CAD) have shown no reduced myocardial infarction (MI) or mortality, the threshold of quantitative myocardial perfusion severity was analyzed for association with reduced death, MI, or stroke after revascularization within 90 d after PET. Methods: In a prospective long-term cohort of stable CAD, regional, artery-specific, quantitative myocardial perfusion by PET, coronary revascularization within 90 d after PET, and all-cause death, MI, and stroke (DMS) at 9-y follow-up (mean ± SD, 3.0 ± 2.3 y) were analyzed by multivariate Cox regression models and propensity analysis. Results: For 3,774 sequential rest-stress PET scans, regional, artery-specific, severely reduced coronary flow capacity (CFC) (coronary flow reserve ≤ 1.27 and stress perfusion ≤ 0.83 cc/min/g) associated with 60% increased hazard ratio for major adverse cardiovascular events and 30% increased hazard of DMS that was significantly reduced by 54% associated with revascularization within 90 d after PET (P = 0.0369), compared with moderate or mild CFC, coronary flow reserve, other PET metrics or medical treatment alone. Depending on severity threshold for statistical certainty, up to 19% of this clinical cohort had CFC severity associated with reduced DMS after revascularization. Conclusion: CFC by PET provides objective, regional, artery-specific, size-severity physiologic quantification of CAD severity associated with high risk of DMS that is significantly reduced after revascularization within 90 d after PET, an association not seen for moderate to mild perfusion abnormalities or medical treatment alone.