Optimal Timing of Pre-emptive Thoracic Endovascular Aortic Repair in Uncomplicated Type B Aortic Dissection: A Network Meta-Analysis.

BACKGROUND: This network meta-analysis compares outcomes of optimal medical therapy (OMT) and pre-emptive thoracic endovascular aortic repair (TEVAR) for uncomplicated type B aortic dissection at different phases of chronicity. METHODS: MEDLINE and EMBASE were searched through November 2023. Pooled short-term outcomes (short-term mortality, perioperative complications) and long-term outcomes (all-cause mortality, aortic-related mortality, aortic re-intervention rates) were calculated. RESULTS: Systematic review identified 17 studies (2 randomized controlled trials, 3 propensity score matching, and 2 inverse probability weighting). Subacute-phase intervention had lower short-term mortality than the acute-phase (hazard ratio [HR] [95% confidence interval [CI]]=0.60 [0.38-0.94], p=0.027). No significant differences were observed in aortic rupture and paraplegia. Acute-phase TEVAR had a higher stroke incidence than subacute-phase intervention (HR [95% CI]=2.63 [1.36-5.09], p=0.042), chronic (HR [95% CI]=2.5 [1.03-6.2], p=0.043), and OMT (HR [95% CI]=1.57 [1.12-2.18], p=0.008). Acute-phase TEVAR had higher long-term all-cause mortality than subacute-phase intervention (HR [95% CI]=1.34 [1.03-1.74], p=0.03). Optimal medical therapy had elevated long-term all-cause mortality compared with subacute-phase TEVAR (HR [95% CI]=1.67 [1.25-2.33], p<0.001) and increased long-term aortic-related mortality vs acute-phase (HR [95% CI]=2.08 [1.31-3.31], p=0.002) and subacute-phase (HR [95% CI]=2.6 [1.62-4.18], p<0.01) interventions. No significant differences were observed in aortic re-intervention rates. CONCLUSIONS: Pre-emptive TEVAR may offer lower all-cause mortality and aortic-related mortality than OMT. Considering lower short-term mortality, perioperative stroke rate, and long-term mortality, our findings support pre-emptive TEVAR during the subacute phase. CLINICAL IMPACT: The optimal timing of pre-emptive thoracic endovascular aortic repair (TEVAR) for uncomplicated type B aortic dissection remains uncertain. This network meta-analysis suggests that the subacute phase (14-90 days from symptom onset) emerges as the optimal timing for pre-emptive TEVAR. This window is associated with lower rates of short-term complications and higher long-term survival rates compared with alternative strategies.

Meta-analysis: Bilateral and Unilateral Cerebral Perfusion in Type A Dissection.

BACKGROUND: This meta-analysis compared the outcomes of bilateral cerebral perfusion (BCP) and unilateral cerebral perfusion (UCP) in aortic surgery for acute type A aortic dissection. METHODS: A systematic literature search identified 12 studies involving 4,547 patients. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated to analyze perioperative characteristics, short-term mortality rates, and postoperative neurological complications. RESULTS: No significant differences were found between the BCP and UCP groups in terms of cardiopulmonary bypass time, aortic cross clamp time, lowest body temperature, and lower body circulatory arrest time. Short-term mortality rates (OR [95% CI] = 0.87 [0.64-1.19], p = 0.40) and permanent neurological deficits (OR [95% CI] = 1.01 [0.69-1.47], p = 0.96) were comparable between the groups. However, subgroup analysis of studies exclusively involving total arch replacement showed a lower short-term mortality rate (OR [95% CI] = 0.42 [0.28-0.63], p < 0.01) and permanent neurological deficits (OR [95% CI] = 0.53 [0.30-0.92], p = 0.03) in the BCP group. The BCP group also had a lower rate of temporary neurological deficits (OR [95% CI] = 0.70 [0.53-0.93], p = 0.01), particularly in studies exclusively involving total arch replacement (OR [95% CI] = 0.58 [0.40-0.85], p < 0.01). CONCLUSION: This meta-analysis suggests that BCP and UCP yield comparable outcomes. However, BCP may be associated with lower short-term mortality rates and reduced incidence of neurological complications, particularly in cases requiring total arch replacement. BCP should be considered as a preferred cerebral perfusion in specific patient populations.

Improved tricuspid regurgitation after transcatheter aortic valve replacement is associated with better survival: Systematic review and meta-analysis with reconstructed time-to-event data.

BACKGROUND: This meta-analysis compared survival outcomes among patients experiencing improvement in untreated significant tricuspid regurgitation (TR) following transcatheter aortic valve replacement (TAVR) for severe aortic stenosis, in contrast to those without improvement. METHODS: MEDLINE and EMBASE were searched through January 2024. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were computed. Employing network meta-analysis, a comparison involving four post-procedural TR categories (improved, no improvement, worsened, and no change) was executed. Subsequently, these categories were amalgamated into two groups (less TR after TAVR and same or greater TR after TAVR), and a standard meta-analysis was conducted. Kaplan-Meier curves depicting long-term all-cause mortality were reconstructed utilizing individual patient data derived from the studies. RESULTS: A systematic review identified seven non-randomized studies encapsulating 698 patients. Network meta-analysis revealed that improved TR after TAVR correlated with significantly lower long-term all-cause mortality compared to the remaining cohorts. Similarly, pooled all-cause mortality of standard meta-analysis demonstrated significant reduction in patients whose TR was sub-baseline than those exhibiting same or greater TR after TAVR (HR [95% CI] = 0.43 [0.32-0.58], p < .01). The hazard ratio, derived from reconstructed time-to-event data, showed a lower long-term all-cause mortality in patients with less TR after TAVR relative to the other cohort (HR [95% CI] = 0.46 [0.32-0.67], p < .01). CONCLUSION: This meta-analysis revealed that improved TR after TAVR correlates with superior long-term survival. The benefits of simultaneous or staged intervention on the tricuspid valve in individuals undergoing TAVR warrant validation in future investigations.

Meta-analysis of central and peripheral cannulation for type A aortic dissection.

BACKGROUND: Acute type A aortic dissection necessitates rapid and effective arterial cannulation techniques for optimal outcomes. This meta-analysis compares the safety and effectiveness of direct aortic cannulation (AoC) with peripheral cannulation (PC) via the femoral or axillary arteries in aortic surgery for acute type A aortic dissection. METHODS: A systematic review following PRISMA guidelines identified 10 retrospective studies encompassing 2518 patients (961 AoC, 1557 PC). Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated to analyze perioperative characteristics, short-term mortality rates, and postoperative complications including stroke and acute kidney injury. RESULTS: Short-term mortality did not significantly differ between AoC and PC (OR [95% CI] = 0.78 [0.61-1.01], p = .06). Likewise, postoperative stroke (OR [95% CI] = 0.86 [0.63-1.17], p = .33) nor acute kidney injury (OR [95% CI] = 1.11 [0.89-1.37], p = .35) showed no significant differences. AoC exhibited shorter operation time whereas there were no significant differences in aortic cross clamp time and cardiopulmonary bypass time between both groups. Our meta-regression analysis, considering the distal extent of aortic replacement, indicated that variations in aortic replacement rates did not significantly impact the observed outcomes. CONCLUSION: AoC is a viable alternative to PC for acute type A aortic dissection. While both approaches offer comparable outcomes, AoC's advantage in shorter operation time warrants thoughtful consideration in clinical practice.

Miniaturized centrifugal ventricular assist device for bridge to decision: Preclinical chronic study in a bovine model.

We developed a novel miniaturized extracorporeal centrifugal pump "BIOFLOAT NCVC (Nipro Corporation Osaka, Japan) as a ventricular assist device (VAD) and performed a preclinical study that is part of the process for its approval as a bridge to decision by the pharmaceutical and medical device agencies. The aim of this study was to assess the postoperative performance, hemocompatibility, and anticoagulative status during an extended period of its use. A VAD system, consisting of a hydrodynamically levitated pump, measuring 64 mm by 131 mm in size and weighing 635 g, was used. We installed this assist system in 9 adult calves (body weight, 90 ± 13 kg): as left ventricular assist device (LVAD) in 6 calves and right ventricular assist device (RVAD) in 3 calves, for over 30 days. Perioperative hemodynamic, hematologic, and blood chemistry measurements were obtained and end-organ effects on necropsy were investigated. All calves survived for over 30 days, with a good general condition. The blood pump was operated at a mean rotational speed and a mean pump flow of 3482 ± 192 rpm and 4.08 ± 0.15 L/min, respectively, for the LVAD and 3902 ± 210 rpm and 4.24 ± 0.3 L/min, respectively, for the RVAD. Major adverse events, including neurological or respiratory complications, bleeding events, and infection were not observed. This novel VAD enabled a long-term support with consistent and satisfactory hemodynamic performance and hemocompatibility in the calf model. The hemodynamic performance, hemocompatibility, and anticoagulative status of this VAD system were reviewed.

Quantification of interventricular dyssynchrony during continuous-flow left ventricular assist device support.

Under continuous-flow left ventricular assist device (CF-LVAD) support, the ventricular volume change and cardiac cycle between the left ventricle (LV) and right ventricle (RV) become dyssynchronous due to the shortening of the LV systole. The purpose of this study was to quantify interventricular dyssynchrony based on different CF-LVAD support conditions and assess its relationship with LV unloading. In this study, we evaluated seven goats (body weight 44.5 ± 6.5 kg) with normal hearts. A centrifugal LVAD was implanted under general anesthesia. We inserted the conductance catheters into the left ventricle (LV) and right ventricle (RV) to assess the volume signal simultaneously. We defined the interventricular dyssynchrony as a signal (increase or decrease) of LV volume (LVV) change opposite to that of RV volume (RVV) (i.e., (dLVV/dt) × (dRVV/dt) < 0). The duration of interventricular dyssynchrony (DYS) was reported as the percentage of time that a heart was in a dyssynchronous state within a cardiac cycle. The mean DYS of normal hearts, hearts with LVAD clamp and hearts supported by LVADs with a bypass rate of 50%, 75% and 100% were 5.6 ± 1.6%, 8.7 ± 2.4%, 8.6 ± 2.8%, 15.1 ± 5.1%, and 25.6 ± 8.0%, respectively. Furthermore, the DYS was found to be associated with the degree of LV stroke volume reduction caused by LV unloading. These findings may be useful for understanding interventricular interactions and physiology during CF-LVAD support. Influences on the right ventricular function and heart failure models warrant further study.

Left heart pressures can be the key to know the limitation of left ventricular assist device support against progression of aortic insufficiency.

Aortic insufficiency (AI) is a worrisome complication under left ventricular assist device (LVAD) support. AI progression causes LVAD-left ventricular (LV) recirculation and can require surgical intervention to the aortic valve. However, the limitations of LVAD support are not well known. Using an animal model of LVAD with AI, the effect of AI progression on hemodynamics and myocardial oxygen metabolism were investigated. Five goats (Saanen 48 ± 2 kg) underwent centrifugal type LVAD, EVAHEART, implantation. The AI model was established by placing a vena cava filter in the aortic valve. Cardiac dysfunction was induced by continuous beta-blockade (esmolol) infusion. Hemodynamic values and myocardial oxygen extraction ratio (O2ER) were evaluated while changing the degree of AI which was expressed as the flow rate of LVAD-LV recirculation (recirculation rate). Diastolic aortic pressure was decreased with AI progression and correlated negatively with the recirculation rate (p = 0.00055). Systolic left ventricular pressure (LVP) and mean left atrial pressure (LAP) were increased with AI progression and correlated positively with the recirculation rate (p = 0.010, 0.023, respectively). LVP and LAP showed marked exponential increases when the recirculation rate surpassed 40%. O2ER was also increased with AI progression and had a significant positive correlation with the recirculation rate (p = 0.000043). O2ER was increased linearly, with no exponential increase. AI progression made it difficult to reduce the cardiac pressure load, worsening myocardial oxygen metabolism. The exponential increase of left heart pressures could be the key to know the limitation of LVAD support against AI progression.

Preclinical animal study of the NIPRO-ventricular assist device for use in pediatric patients.

Although the outcomes of patients with end-stage heart failure treated with implantable left ventricular assist devices have improved, extracorporeal left ventricular assist devices continue to play an important role, especially in pediatric patients. The present study aimed to examine the long-term biocompatibility of a small-sized extracorporeal pneumatic left ventricular assist device (NIPRO-LVAD) used in a 30- to 90-day animal experiment. The NIPRO-LVAD was designed for pediatric patients or small-sized adults. The left ventricular assist device system was installed in four adult Shiba goats weighing 25.7 ± 4.78 kg via a left thoracotomy. The outflow graft was sewn to the descending aorta and the inflow cannula was placed in the left ventricle through the left ventricular apex. Oral antiplatelet (aspirin) and oral anticoagulation therapies (warfarin) were also administered. Three out of four animals survived for a 30-day period and two goats survived for 90 days. One animal was killed early because of low pump flow due to obstruction of the inflow cannula by a left ventricular endocardial vegetation. The blood pump exhibited sufficient hydrodynamic performance with blood flows of 1.5-2.0 L/min. The animals' laboratory values were within normal limits by postoperative day 7. There was no significant thrombus formation on the housing, diaphragm, or valves of the explanted pumps. Based on the biocompatibility demonstrated in this animal study, the explanted small-sized pump may be suitable for use in left ventricular assist device systems for pediatric patients.

Novel temporary left ventricular assist system with hydrodynamically levitated bearing pump for bridge to decision: initial preclinical assessment in a goat model.

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. We developed a new temporary left ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing. We used three adult goats (body weight, 58-68 kg) to investigate the 30-day performance and hemocompatibility of the newly developed left ventricular assist system, which included the pump, inflow and outflow cannulas, the extracorporeal circuit, and connectors. Hemodynamic, hematologic, and blood chemistry measurements were investigated as well as end-organ effect on necropsy. All goats survived for 30 days in good general condition. The blood pump was operated at a rotational speed of 3000-4500 rpm and a mean pump flow of 3.2 ± 0.6 L min. Excess hemolysis, observed in one goat, was due to the inadequate increase in pump rotational speed in response to drainage insufficiency caused by continuous contact of the inflow cannula tip with the left ventricular septal wall in the early days after surgery. At necropsy, no thrombus was noted in the pump, and no damage caused by mechanical contact was found on the bearing. The newly developed temporary left ventricular assist system using a disposable centrifugal pump with hydrodynamic bearing demonstrated consistent and satisfactory hemodynamic performance and hemocompatibility in the goat model.

What Is the Optimal Setting for a Continuous-Flow Left Ventricular Assist Device in Severe Mitral Regurgitation?

Excessive left ventricular (LV) volume unloading can affect right ventricular (RV) function by causing a leftward shift of the interventricular septum in patients with mitral regurgitation (MR) receiving left ventricular assist device (LVAD) support. Optimal settings for the LVAD should be chosen to appropriately control the MR without causing RV dysfunction. In this study, we assessed the utility of our electrocardiogram-synchronized rotational speed (RS) modulation system along with a continuous-flow LVAD in a goat model of MR. We implanted EVAHEART devices after left thoracotomy in six adult goats weighing 66.4 ± 10.7 kg. Severe MR was induced through inflation of a temporary inferior vena cava filter placed within the mitral valve. We evaluated total flow (TF; the sum of aortic flow and pump flow [PF]), RV fractional area change (RVFAC) calculated by echocardiography, left atrial pressure (LAP), LV end-diastolic pressure (LVEDP), LV end-diastolic volume (LVEDV), and LV stroke work (LVSW) with a bypass rate (PF divided by TF) of 100% under four conditions: circuit-clamp, continuous mode, co-pulse mode (increased RS during systole), and counter-pulse mode (increased RS during diastole). TF tended to be higher in the counter-pulse mode. Moreover, RVFAC was significantly higher in the counter-pulse mode than in the co-pulse mode, whereas LAP was significantly lower in all driving modes than in the circuit-clamp condition. Furthermore, LVEDP, LVEDV, and LVSW were significantly lower in the counter-pulse mode than in the circuit-clamp condition. The counter-pulse mode of our RS modulation system used with a continuous-flow LVAD may offer favorable control of MR while minimizing RV dysfunction.

Influence of a Rotational Speed Modulation System Used With an Implantable Continuous-Flow Left Ventricular Assist Device on von Willebrand Factor Dynamics.

We have developed a rotational speed (RS) modulation system for a continuous-flow left ventricular assist device (EVAHEART) that can change RS in synchronization with a patient's electrocardiogram. Although EVAHEART is considered not to cause significant acquired von Willebrand syndrome, there remains a concern that the repeated acceleration and deceleration of the impeller may degrade von Willebrand factor (vWF) multimers. Accordingly, we evaluated the influence of our RS modulation system on vWF dynamics. A simple mock circulation was used. The circulation was filled with whole bovine blood (650 mL), and the temperature was maintained at 37 ± 1°C. EVAHEART was operated using the electrocardiogram-synchronized RS modulation system with an RS variance of 500 rpm and a pulse frequency of 60 bpm (EVA-RSM; n = 4). The pumps were operated at a mean flow rate of 5.0 ± 0.2 L/min against a mean pressure head of 100 ± 3 mm Hg. The continuous-flow mode of EVAHEART (EVA-C; n = 4) and ROTAFLOW (ROTA; n = 4) was used as controls. Whole blood samples were collected at baseline and every 60 min for 6 h. Complete blood counts (CBCs), normalized indexes of hemolysis (NIH), vWF antigen (vWF:Ag), vWF ristocetin cofactor (vWF:Rco), the ratio of vWF:Rco to vWF:Ag (Rco/Ag), and high molecular weight multimers (HMWM) of vWF were evaluated. There were no significant changes in CBCs throughout the 6-h test period in any group. NIH levels of EVA-RSM, EVA-C, and ROTA were 0.0035 ± 0.0018, 0.0031 ± 0.0007, and 0.0022 ± 0.0011 g/100 L, respectively. Levels of vWF:Ag, vWF:Rco, and Rco/Ag did not change significantly during the test. Immunoblotting analysis of vWF multimers showed slight degradation of HMWM in all groups, but there were no significant differences between groups in the ratios of HMWM to low molecular weight multimers, calculated by densitometry. This study suggests that our RS modulation system used with EVAHEART does not have marked adverse influences on vWF dynamics. The low NIH and the absence of significant decreases in CBCs indicate that EVAHEART is hemocompatible, regardless of whether it is operated with the RS modulation system.

[Infectious endocarditis complicated with preoperative infectious intracranial aneurysm;report of a case].

A 44-year-old man was admitted with the diagnosis of active infective endocarditis( IE) due to Streptococcus mitis, complicated with infectious intracranial aneurysm. Preoperative echocardiography showed mobile vegetation on the mitral leaflet, size of which was 20 mm. The magnetic resonance imaging( MRI) demonstrated that the size of aneurysm was increasing, and infectious intracranial aneurysm was treated surgically. Twenty one days after the operation, the mitral valve plasty was performed. He was discharged on foot without any neurological findings. The duration between the brain surgery and the cardiac surgery was thought to be important to prevent the new neurological complication.

[Restenosis following descending aortic replacement for coarctation of the aorta; report of a case].

We report a case of a 44-year-old man with restenosis of coarctation of aorta (CoA). He had a history of descending aortic replacement for CoA using a graft 14 mm in diameter at 29 years ago. He had reoperation because of pressure gradient of 61 mmHg across the graft and intermittent claudication. Reoperation was done under unilateral lung ventilation with lung collapsed, through 3th and 5th interspace thoracotomy. Left lung adhesion was carefully released with an ultrasonically vibrating scalpel. After full heparinization, femoro-femoral bypass was started and descending aorta was clamped. The old graft was excised, and descending aortic replacement was done with a new graft of 26 mm in a diameter. His postoperative course was uneventful. The intermittent claudication disappeared.

[Successful excision of a left ventricular fibroma in an adult patient; report of a case].

A 55-year-old man was referred with a diagnosis of a left ventricular thrombus. Echocardiography revealed that he had a thrombus in the free wall of the left ventricle. Under cardiopulmonary bypass, we removed the intramural tumor. After the removal, the defect was repaired by Dor operation. Pathological examination revealed the tumor was a cardiac fibroma. He is doing well without any troubles 3 years after the operation.

[Graft replacement under percutaneous cardiopulmonary system for traumatic aortic rupture with multiple injuries].

We report a case of traumatic aortic rupture with multiple injuries. A 20-year-old man was transferred to our hospital. He was suffering from traumatic thoracic aortic rupture with multiple injuries (femoral fracture, pelvis fracture and so 4th) due to a traffic accident. Enhanced computed tomography revealed leakage from the aortic isthmus and hematoma in the surrounding area. Emergency operation was performed. The left 4th intercostal thoracotomy was performed and a lacerated foramen was observed across the lesser curvature of the aortic isthmus. The affected site was replaced by a prosthetic graft under percutaneous cardiopulmonary system. He was treated with open fixation of the right femur 11 days after the 1st operation. The postoperative recovery was generally uneventful and he was discharged on the 51st hospital day.

Artificial Lungs for Lung Failure in the Era of COVID-19 Pandemic: Contemporary Review.

In patients with severe acute respiratory distress syndrome caused by coronavirus 2019 (COVID-19), mortality remains high despite optimal medical management. Extracorporeal membrane oxygenation (ECMO) has been widely used to support such patients. ECMO is not a perfect solution; however, there are several limitations and serious complications associated with ECMO use. Moreover, the overall short-term mortality rate of patients with COVID-19 supported by ECMO is high (~30%). Some patients who survive severe acute respiratory distress syndrome have chronic lung failure requiring oxygen supplementation, long-term mechanical ventilation, or ECMO support. Although lung transplant remains the most effective treatment for patients with end-stage lung failure from COVID-19, optimal patient selection and transplant timing for patients with COVID-19-related lung failure are not clear. Access to an artificial lung (AL) that can be used for long-term support as a bridge to transplant, bridge to recovery, or even destination therapy will become increasingly important. In this review, we discuss why the COVID-19 pandemic may drive progress in AL technology, challenges to AL implementation, and how some of these challenges might be overcome.

Combination of polycarboxybetaine coating and factor XII inhibitor reduces clot formation while preserving normal tissue coagulation during extracorporeal life support.

Blood contact with high surface area medical devices, such as dialysis and extracorporeal life support (ECLS), induces rapid surface coagulation. Systemic anticoagulation, such as heparin, is thus necessary to slow clot formation, but some patients suffer from bleeding complications. Both problems might be reduced by 1) replacing heparin anticoagulation with artificial surface inhibition of the protein adsorption that initiates coagulation and 2) selective inhibition of the intrinsic branch of the coagulation cascade. This approach was evaluated by comparing clot formation and bleeding times during short-term ECLS using zwitterionic polycarboxybetaine (PCB) surface coatings combined with either a potent, selective, bicyclic peptide inhibitor of activated Factor XII (FXII900) or standard heparin anticoagulation. Rabbits underwent venovenous ECLS with small sham oxygenators for 60 min using three means of anticoagulation (n = 4 ea): (1) PCB coating + FXII900 infusion, (2) PCB coating + heparin infusion with an activated clotting time of 220-300s, and (3) heparin infusion alone. Sham oxygenator blood clot weights in the PCB + FXII900 and PCB + heparin groups were 4% and 25% of that in the heparin group (p < 10-6 and p < 10-5), respectively. At the same time, the bleeding time remained normal in the PCB + FXII900 group (2.4 ± 0.2 min) but increased to 4.8 ± 0.5 and 5.1 ± 0.7 min in the PCB + heparin and heparin alone groups (p < 10-4 and 0.01). Sham oxygenator blood flow resistance was significantly lower in the PCB + FXII900 and PCB + heparin groups than in the heparin only group (p < 10-6 and 10-5). These results were confirmed by gross and scanning electron microscopy (SEM) images and fibrinopeptide A (FPA) concentrations. Thus, the combined use of PCB coating and FXII900 markedly reduced sham oxygenator coagulation and tissue bleeding times versus the clinical standard of heparin anticoagulation and is a promising anticoagulation method for clinical ECLS.

Zwitterionic poly-carboxybetaine coating reduces artificial lung thrombosis in sheep and rabbits.

Current artificial lungs fail in 1-4 weeks due to surface-induced thrombosis. Biomaterial coatings may be applied to anticoagulate artificial surfaces, but none have shown marked long-term effectiveness. Poly-carboxybetaine (pCB) coatings have shown promising results in reducing protein and platelet-fouling in vitro. However, in vivo hemocompatibility remains to be investigated. Thus, three different pCB-grafting approaches to artificial lung surfaces were first investigated: 1) graft-to approach using 3,4-dihydroxyphenylalanine (DOPA) conjugated with pCB (DOPA-pCB); 2) graft-from approach using the Activators ReGenerated by Electron Transfer method of atom transfer radical polymerization (ARGET-ATRP); and 3) graft-to approach using pCB randomly copolymerized with hydrophobic moieties. One device coated with each of these methods and one uncoated device were attached in parallel within a veno-venous sheep extracorporeal circuit with no continuous anticoagulation (N = 5 circuits). The DOPA-pCB approach showed the least increase in blood flow resistance and the lowest incidence of device failure over 36-hours. Next, we further investigated the impact of tip-to-tip DOPA-pCB coating in a 4-hour rabbit study with veno-venous micro-artificial lung circuit at a higher activated clotting time of 220-300 s (N ≥ 5). Here, DOPA-pCB reduced fibrin formation (p = 0.06) and gross thrombus formation by 59% (p < 0.05). Therefore, DOPA-pCB is a promising material for improving the anticoagulation of artificial lungs. STATEMENT OF SIGNIFICANCE: Chronic lung diseases lead to 168,000 deaths each year in America, but only 2300 lung transplantations happen each year. Hollow fiber membrane oxygenators are clinically used as artificial lungs to provide respiratory support for patients, but their long-term viability is hindered by surface-induced clot formation that leads to premature device failure. Among different coatings investigated for blood-contacting applications, poly-carboxybetaine (pCB) coatings have shown remarkable reduction in protein adsorption in vitro. However, their efficacy in vivo remains unclear. This is the first work that investigates various pCB-coating methods on artificial lung surfaces and their biocompatibility in sheep and rabbit studies. This work highlights the promise of applying pCB coatings on artificial lungs to extend its durability and enable long-term respiratory support for lung disease patients.

Artificial Lungs for Lung Failure: JACC Technology Corner.

Although lung transplantation is an effective treatment for end-stage lung failure, its limitations have led to renewed interest in artificial lung support for patients with lung failure. The use of ventricular assist devices has significantly improved the quality of life and survival of patients with end-stage heart failure. In contrast, there are no devices that can be used long term as destination therapy for end-stage lung failure, and there is a strong need for them. Extracorporeal membrane oxygenation is widely used as a temporary treatment for acute lung failure and as a bridge to lung transplant. Many patients with advanced lung failure cannot return home with good quality of life once they are hospitalized. In this review, the authors discuss the history, status, and future of artificial lungs, focusing on long-term artificial respiratory support as a destination therapy. Respiratory assist devices, such as artificial lungs, could eventually become analogous to ventricular assist devices.

Implanted In-Body Tissue-Engineered Heart Valve Can Adapt the Histological Structure to the Environment.

Tissue-engineered heart valves (TEHVs) are expected to be viable grafts. However, it is unknown whether they transit their histological structure after implantation. We developed a novel autologous TEHV (named stent biovalve) for transcatheter implantation, using in-body tissue engineering based on a tissue encapsulation phenomenon. In this study, a time-course histological transition of implanted biovalves was investigated in goats. Three types of stent biovalves were prepared by 2 month embedding of plastic molds mounted with metallic stents, in the subcutaneous spaces. After extracting the molds with tissue and removing the molds only, stent biovalves were constituted entirely from the connective tissues. Stent biovalves were implanted in the aortic or pulmonary valve position of other goats with transcatheter technique. In each animal, the stent biovalve was explanted at 1 month step (from 1 to 6 months) or as long as possible. Total 12 goats (five for aortic and seven for pulmonary) were successfully implanted. The maximum duration became 19 months as a result. Even then the leaflets of the biovalves kept their shape and elasticity, and neither calcification nor thrombi were observed in any cases and duration. Histology showed the recipients' cells covering the laminar surface of the leaflets like the endothelium even after 1 month. The cells have also migrated in the leaflets gradually and finally constructed characteristic 3 layered tissues like native leaflets. Implanted stent biovalves can adapt their histological structure to the environment. They have a potential as viable grafts keeping better function and biocompatibility.