Spinal Cord Infarction With Prolonged Femoral Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: There have been sporadic reports of ischemic spinal cord injury (SCI) during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. The authors observed a troubling pattern of this catastrophic complication and evaluated the potential mechanisms of SCI related to ECMO. DESIGN: This study was a case series. SETTING: This study was performed at a single institution in a University setting. PARTICIPANTS: Patients requiring prolonged VA-ECMO were included. INTERVENTIONS: No interventions were done. This was an observational study. MEASUREMENTS AND MAIN RESULTS: Four hypotheses of etiology were considered: (1) hypercoagulable state/thromboembolism, (2) regional hypoxia/hypocarbia, (3) hyperperfusion and spinal cord edema, and (4) mechanical coverage of spinal arteries. The SCI involved the lower thoracic (T7-T12 level) spinal cord to the cauda equina in all patients. Seven out of 132 (5.3%) patients with prolonged VA-ECMO support developed SCI. The median time from ECMO cannulation to SCI was 7 (range: 6-17) days.There was no evidence of embolic SCI or extended regional hypoxia or hypocarbia. A unilateral, internal iliac artery was covered by the arterial cannula in 6/7 86%) patients, but flow into the internal iliac was demonstrated on imaging in all available patients. The median total flow (ECMO + intrinsic cardiac output) was 8.5 L/min (LPM), and indexed flow was 4.1 LPM/m2. The median central venous oxygen saturation was 88%, and intracranial pressure was measured at 30 mmHg in one patient, suggestive of hyperperfusion and spinal cord edema. CONCLUSIONS: An SCI is a serious complication of extended peripheral VA-ECMO support. Its etiology remains uncertain, but the authors' preliminary data suggested that spinal cord edema from hyperperfusion or venous congestion could contribute.

Translocation of the Mitral Valve in an Acute Large Animal Model.

Current repair options for functional mitral regurgitation (FMR) are not durable and do not adequately address underlying pathophysiology including leaflet tethering and insufficient coaptation. The feasibility of mitral valve translocation as a repair strategy for FMR was examined in normal swine. Seven pigs (median 62 kg, IQR 55-65 kg) with normal cardiac function were implanted with a 1-cm frustum-shaped pericardial patch inserted between the native mitral annulus and intact mitral leaflets. Operative survival was 100% with no post-procedure mitral stenosis, systolic anterior motion, or central mitral regurgitation observed on echocardiography. Post-translocation mean gradient was 3.5 mmHg (IQR 1.5-4 mmHg); trace or mild suture line leaks on the atrial suture line were noted in 5/7 pigs. Median leaflet coaptation increased from 2.4 (IQR 2.1-4.3 mm) to 12.4 mm (IQR 10.8-13.4 mm) after translocation (P = 0.016). Translocation dramatically increases leaflet coaptation without impairing diastolic function in animals with normal left ventricular function and is a promising technique for repair of FMR. Implantation of a 1.0-cm circumferential pericardial patch (mitral valve translocation) increases leaflet coaptation in a normal animal model.

Veno-Arterial Extracorporeal Membrane Oxygenation for Pulmonary Embolism after Systemic Thrombolysis.

Massive pulmonary embolism (PE) is a life-threatening condition with a high mortality. Both systemic thrombolytics and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) have been used in the management of massive PE. However, the safety of VA- ECMO in the setting of recent thrombolytic administration is not clear. The purpose of this study is to analyze the outcomes of patients who received VA-ECMO in the setting of systemic thrombolytics (ST). A single institution retrospective study of PE patients treated with VA-ECMO between December 2015 and December 2020 was performed. Patients who received ST were compared with those who did not receive ST. Outcomes, including mortality, major bleeding, duration of mechanical ventilation, need for renal replacement therapy, and length of hospital stay, were compared. A total of 83 patients with PE required VA-ECMO support and 18 of these received systemic thrombolytics. There was no statistically significant difference in survival to discharge between the patients who received ST compared with those who did not (88.9% vs 84.6%; p = 0.94). Major bleeding events occurred more often in patients who received ST (61.1% vs 26.2%; p = 0.01). There was no significant difference in time on mechanical ventilation, need for renal replacement therapy, or length of stay between the groups. Reasonable survival can be achieved despite an increased frequency of major bleeding events in patients that receive ST prior to VA-ECMO for PE. ST administration should not be considered an absolute contraindication to VA-ECMO. Further multi-center studies are needed to corroborate these findings.

Mitral Valve Translocation: A Novel Operation for the Treatment of Secondary Mitral Regurgitation.

BACKGROUND: Conventional annuloplasty repair of secondary (functional) ischemic mitral regurgitation (IMR) is associated with a 60% recurrence of moderate or greater mitral regurgitation at 2 years. We developed a novel repair technique for IMR that addresses the underlying geometric alterations of the mitral valve apparatus and compared outcomes with those of conventional repair in a swine model. METHODS: Chronic IMR was induced by percutaneous embolization of the circumflex artery. Swine with severe IMR (median 9 weeks after infarction) underwent undersized rigid annuloplasty (n = 5) or translocation repair (n = 6). Translocation repair consisted of detaching the mitral valve en bloc at the annulus, creating a 1 cm wide frustum-shaped pericardial patch, and suturing the outer circumference of the patch to the annulus and inner circumference to the mitral valve. RESULTS: Operative survival was 92% (11 of 12). All animals had none/trace residual central mitral regurgitation, and mean inflow gradients were similar (1 mm Hg [interquartile range, 1 to 2] vs 2 mm Hg [interquartile range, 1 to 2]; P = .75) in the annuloplasty and translocation groups, respectively. Median coaptation length marginally improved in conventional swine (3 to 4 mm, P = .05), but dramatically improved in translocation swine (3 to 8 mm, P = .003). Posterior leaflet angle increased from 39 to 80 degrees (P = .05) in annuloplasty swine but decreased from 50 to 31 degrees (P = .03) in translocation swine. The posterior leaflet was immobile after annuloplasty but had preserved motion after translocation (excursion, 1 degree vs 24 degrees; P = .045). CONCLUSIONS: Mitral valve translocation effectively treats mitral regurgitation by relieving leaflet tethering. Compared with annuloplasty, mitral valve translocation creates a larger surface of coaptation and preserves leaflet mobility without compromising diastolic function.

Ultrasound-assisted catheter directed thrombolysis for pulmonary embolus during extracorporeal membrane oxygenation.

BACKGROUND: Acute pulmonary embolism (PE) is the third most common cause of cardiovascular death. For patients who are hemodynamically unstable, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support has been shown to provide hemodynamic stability, and allow time for definitive treatment and recovery. Ultrasound-assisted catheter directed thrombolysis (USAT) has the potential to be a safe adjunct and expedite right ventricular (RV) recovery for patients requiring VA-ECMO for PE. METHODS: A review of all VA-ECMO patients from January 2017 to September 2019 was performed. A total of 49 of these patients were cannulated due to a PE. USAT therapy was used as an adjunct in 6 (12%) of these patients. These 6 patients were given standardized USAT therapy with EKOs catheters at 1 mg/h of tissue plasminogen activator with an unfractionated heparin infusion for additional systemic anticoagulation. Outcomes, including in-hospital death, 90-day survival, RV recovery, and complications, were examined in the cohort of patients that received USAT as an adjunct to ECMO. RESULTS: Median age was 54 years old. Five of the six patients presented with a massive PE and had a PE severity score of Class V. One patient presented with a submassive PE with a Bova score of 2, but was cannulated to VA-ECMO in the setting of worsening RV function. All patients demonstrated recovery of RV function, were free from in-hospital death, and were alive at 90-day follow-up. CONCLUSION: Ekosonic endovascular system therapy may be a safe and feasible adjunct for patients on VA-ECMO for PE, and allow for survival with RV recovery with minimal complications.

Inflow Cannula Position Influences Improvement in Mitral Regurgitation After Ventricular Assist Device Implantation.

Significant residual mitral regurgitation (MR) after left ventricular assist device (LVAD) implantation has been associated with increased morbidity and mortality. The effect of cannula position on improvement of preexisting MR has yet to be evaluated. Consecutive patients who underwent centrifugal LVAD implantation with >mild preoperative MR and without concomitant mitral repair were reviewed. Left ventricular assist device position was determined by the angle between actual and ideal inflow cannula on computed tomography. The magnitudes of angles (anterior and lateral angle) were added to form an LVAD position assessment (LVADpa). Mitral regurgitation was numerically classified, and improvement in MR was determined by difference in MR preoperatively to MR >1 month postoperatively with a median of 162 (interquartile range: 78-218) days. The primary analysis examined the relationship between LVADpa and postoperative MR. Forty-one patients were identified with >mild preoperative functional MR. Mean age was 51 ± 13 years with an ejection fraction of 16 ± 4%. Overall, MR improved from moderate-severe preoperatively to mild postoperatively (p < 0.001). On multivariable analysis, higher LVADpa deviation was associated with greater postoperative MR (odds ratio [OR] = 2.29, p = 0.005) and higher 1-month pulsatility index was associated with lower postoperative MR (OR = 0.47, p = 0.011). Inflow cannula position during centrifugal LVAD implantation is an important determinant of postoperative MR.

Initial Clinical Experience With Mitral Valve Translocation for Secondary Mitral Regurgitation.

BACKGROUND: Functional (secondary) mitral regurgitation (FMR) results from altered geometry of the mitral valve apparatus. Repair with restrictive mitral annuloplasty is associated with high rates of recurrent mitral regurgitation (MR). We developed a novel operative repair for FMR that translocates the intact mitral valve towards the apex. METHODS: The mitral valve was detached circumferentially and translocated into the ventricle with a frustum-shaped glutaraldehyde-treated autologous pericardial patch. Clinical and echocardiographic follow-up was performed. RESULTS: Fifteen consecutive patients with FMR (mean age, 59 years; 67% female) had mitral valve translocation between 2018 and 2020. Preoperative mean ejection fraction, left ventricular end-diastolic dimension, and systolic pulmonary artery pressure were 40% ± 11%, 59 ± 8 mm, and 49 ± 21 mm Hg, respectively; 33% had atrial fibrillation. Cardiomyopathy was ischemic in 4 and nonischemic in 11. Concomitant procedures included tricuspid valve operation (n = 8), coronary artery bypass grafting (n = 4), and atrial fibrillation ablation (n = 5). Post bypass transesophageal echocardiogram demonstrated none/trace MR in all patients and mean gradient of 3 mm Hg (interquartile range, 2-4 mm Hg). Mean leaflet extent of coaptation was 14 ± 2 mm (range, 11-17 mm). There was no postoperative mortality, stroke, or renal failure. Predismissal echocardiography showed none/trace MR in 14 patients and mild MR in 1. One patient underwent successful late rerepair of a suture line leak. Twelve patients were alive at latest follow-up and MR at 1 and 6 months was mild or less in all patients with mean leaflet extent of coaptation of 14 ± 2 mm (range, 12-16 mm) at 6 months. CONCLUSIONS: Mitral valve translocation creates a large surface of coaptation and effectively corrects FMR. Further study is needed to demonstrate the long-term durability and clinical utility of this operation.

Development of a Reproducible Swine Model of Chronic Ischemic Mitral Regurgitation: Lessons Learned.

BACKGROUND: Durability of mitral valve repair for ischemic mitral regurgitation (IMR) remains poor. We established a swine model of chronic IMR, and describe the methods and lessons learned from this model. METHODS: Thirty-five swine underwent percutaneous myocardial infarction with ethanol ablation of the circumflex or obtuse marginal (OM) arteries. Swine were followed with routine echocardiography for the development of severe IMR. Once severe IMR was established, swine underwent mitral valve operations on cardiopulmonary bypass. After operation, swine were survived up to 7 weeks. Angiographic and echocardiographic features of swine who developed severe IMR (IMR swine) and those who did not (non-IMR swine) were compared. RESULTS: The median number of OM arteries was 3, with 2 OM arteries infarcted. Acute survival after the myocardial infarction was 74% (26 of 35) with 3 (9%) early, postoperative deaths. Among the 23 swine with follow-up to determine IMR status, 14 of 23 (61%) developed significant IMR. Among IMR pigs, left ventricular (LV) ejection fraction decreased from 65% pre-myocardial infarction to 45% pre-mitral valve intervention (P < .001). Among non-IMR swine, LV ejection fraction decreased nonsignificantly from baseline (60%) to latest follow-up (55%) (P = .443). LV end-diastolic dimension (P = .039), wall motion score (P = .027), global circumferential strain (P = .014), and global longitudinal strain (P = .023) were significantly worse in IMR compared with non-IMR swine. CONCLUSIONS: A reproducible percutaneous model of severe IMR in swine is feasible with a guided anesthetic and perioperative approach. This model can serve as a platform to better understand the mechanism of IMR and subsequently to test novel repair techniques.

Neomedia Aortic Root Repair for Type A Aortic Dissection Despite Anomalous Right Coronary Artery.

An anomalous right coronary artery arising from the left coronary sinus is a rare anatomic variant. Here we report a patient who presented with an acute type A dissection and underwent successful aortic root reconstruction with resuspension of the aortic valve and neomedia creation in the presence of an anomalous right coronary artery with a good clinical outcome.

Sutureless Closure of Arterial Cannulation Sites.

OBJECTIVE: Percutaneous femoral cannulation for venoarterial extracorporeal membrane oxygenation (ECMO) is commonly performed but percutaneous removal of arterial cannulas has not been broadly accepted. We hypothesized that a system that allows endovascular access to ECMO circuits along with the MANTA® large-bore vascular closure device could be used to successfully close arterial ECMO cannulation sites in a large animal model. METHODS: Yorkshire swine (40 to 60 kg, n = 2) were used for this study. In the first swine, the infrarenal abdominal aorta was exposed. The aorta was cannulated once using a 15 Fr cannula and twice with a 19 Fr arterial cannula. A novel adaptor system that facilitates endovascular access to ECMO circuits was connected, and a 0.035″ Benston wire was placed through the adaptor and guided into the aorta. The cannula was removed over the wire and manual pressure was applied. The MANTA® sheath was inserted over the wire followed by the closure unit and was deployed. The process was repeated at 2 separate sites. A similar experiment was performed in a second swine, but through a median sternotomy to cannulate the ascending aorta. RESULTS: Good hemostasis was achieved at all cannulation sites. Angiography demonstrated unobstructed flow across all closure sites with no evidence of extravasation. CONCLUSIONS: The data presented here support the use of the MANTA® vascular closure device for the closure of arterial cannulation sites following ECMO decannulation and demonstrates utility of a novel adaptor system for establishing endovascular access in this context.

Strategic application of modular risk components to safely increase lung transplantation volume.

OBJECTIVES: Considerable growth of individual lung transplant programs remains challenging. We hypothesized that the systematic implementation of modular risk components to a lung transplantation program would allow for expeditious growth without increasing mortality. METHODS: All consecutive patients placed on the lung transplantation waitlist were reviewed. Patients were stratified by an 18-month period surrounding the systematic implementation of the modular risk components Era 1 (1/2014-6/2015) and Era 2 (7/2015-12/2016). Modular risk components were separately evaluated for donors, recipients, and perioperative features. RESULTS: One hundred and thirty-two waitlist patients (Era 1: 48 and Era 2: 84) and 100 transplants (Era 1: 32 and Era 2: 68) were identified. There was a trend toward decreased waitlist mortality (P = .07). In Era 2, the use of ex vivo lung perfusion (P = .05) and donor-recipient over-sizing (P = .005) significantly increased. Moreover, transplantation with a lung allocation score greater than 70 (P = .05), extracorporeal support (P = .06), and desensitization (P = .008) were more common. Transplant rate significantly improved from Era 1 to Era 2 (325 vs 535 transplants per 100 patient years, P = .02). While primary graft dysfunction (PGD) grade 3 at 72 hours (P = .05) was significantly higher in Era 2, 1-year freedom from rejection was similar (86% vs 90%, P = .69) and survival (81% vs 95%, P = .02) was significantly greater in Era 2. CONCLUSIONS: The systematic implementation of a modular risk components to a lung transplantation program can result in a significant increase in center volume. However, measures to mitigate an expected increase in the incidence of PGD must be undertaken to maintain excellent short and midterm outcomes.

Left ventricular assist device implantation may be feasible in appropriately selected patients with severe renal insufficiency.

OBJECTIVES: Severe renal insufficiency is considered a relative contraindication to left ventricular assist device (LVAD) implantation. After establishing an algorithmic approach to these patients, we hypothesized that LVAD implantation with severe renal insufficiency could be performed without increasing morbidity or mortality. METHODS: All consecutive patients (July 2015-December 2017) who underwent LVAD implantation were retrospectively reviewed. Patients were stratified by preoperative glomerular filtration rate (GFR): ≤30 mL/min/1.73 m2 (low-GFR) and >30 mL/min/1.73 m2 (high-GFR). Preoperative optimization included aggressive inotropic support and temporary mechanical circulatory support before LVAD implantation in any patient with an acute component of renal insufficiency. All patients with a preoperative GFR ≤15 mL/min/1.73 m2 were prophylactically initiated on temporary renal replacement therapy postoperatively. The primary outcome was Kaplan-Meier 1-year survival. RESULTS: Fifty-eight patients (21 with low-GFR and 37 with high-GFR) were identified. Patients in the low-GFR cohort had a significantly higher median Interagency Registry for Mechanically Assisted Circulatory Support score and worse preoperative end-organ function. Preoperative optimization resulted in an increase in GFR to >30 mL/min/1.73 m2 in 11 out of 21 patients from the low-GFR cohort. Inotrope days, ventilator time, intensive care unit length of stay, and hospital length of stay were not significantly different between the groups. Kaplan-Meier 1-year survival was 81% in the low-GFR cohort and 86% in the high-GFR cohort (P = .98). Subset analysis of GFR ≤15 mL/min/1.73 m2 (n = 11) and ≥60 mL/min/1.73 m2 (n = 19) demonstrated identical 1-year survival (89% vs 89%; P = .91). CONCLUSIONS: LVAD implantation in carefully selected patients with severe renal insufficiency can be performed without increasing midterm morbidity or mortality. This strategy may serve as a successful option to bridge patients to transplantation or destination therapy.

The impact of shear stress on device-induced platelet hemostatic dysfunction relevant to thrombosis and bleeding in mechanically assisted circulation.

The aim of this study was to examine the impact of the nonphysiological shear stress (NPSS) on platelet hemostatic function relevant to thrombosis and bleeding in mechanically assisted circulation. Fresh human blood was circulated for four hours in in vitro circulatory flow loops with a CentriMag blood pump operated under a flow rate of 4.5 L/min against three pressure heads (70 mm Hg, 150 mm Hg, and 350 mm Hg) at 2100, 2800, and 4000 rpm, respectively. Hourly blood samples from the CentriMag pump-assisted circulation loops were collected and analyzed for glycoprotein (GP) IIb/IIIa activation and receptor shedding of GPVI and GPIbα on the platelet surface with flow cytometry. Adhesion of platelets to fibrinogen, collagen, and von Willebrand factor (VWF) of the collected blood samples was quantified with fluorescent microscopy. In parallel, mechanical shear stress fields within the CentriMag pump operated under the three conditions were assessed by computational fluid dynamics (CFD) analysis. The experimental results showed that levels of platelet GPIIb/IIIa activation and platelet receptor shedding (GPVI and GPIbα) in the blood increased with increasing the circulation time. The levels of platelet activation and loss of platelet receptors GPVI and GPIbα were consistently higher with higher pressure heads at each increasing hour in the CentriMag pump-assisted circulation. The platelet adhesion on fibrinogen increased with increasing the circulation time for all three CentriMag operating conditions and was correlated well with the level of platelet activation. In contrast, the platelet adhesion on collagen and VWF decreased with increasing the circulation time under all the three conditions and was correlated well with the loss of the receptors GPVI and GPIbα on the platelet surface, respectively. The CFD results showed that levels of shear stresses inside the CentriMag pump under all three operating conditions exceeded the maximum level of shear stress in the normal physiological circulation and were strongly dependent on the pump operating condition. The level of platelet activation and loss of key platelet adhesion receptors (GPVI and GPIbα) were correlated with the level of NPSS generated by the CentriMag pump, respectively. In summary, the level of NPSS associated with pump operating condition is a critical determinant of platelet dysfunction in mechanically assisted circulation.

Evaluation of an autoregulatory ECMO system for total respiratory support in an acute ovine model.

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 autoregulatory 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 (SpO2  = 96.3 % ± 4.29, pH 7.44 ± 0.09, pCO2  = 38.9 ± 9.9 mm Hg, and pO2 =237.9 ± 123.6 mm Hg) during simulated respiratory distress. Acceptable correlation between oxygenator exhaust gas CO2 and oxygenator outlet pCO2 were observed (R2  = 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.

The Role of a Disintegrin and Metalloproteinase Proteolysis and Mechanical Damage in Nonphysiological Shear Stress-Induced Platelet Receptor Shedding.

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.

Degenerative Mitral Valve Repair Simplified: An Evolution to Universal Artificial Cordal Repair.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Artificial cordal repair for all patients with degenerative MR simplifies MV repair and yields equivalent, excellent outcomes compared with a tailored resectional approach.

The role of PI3K/Akt signaling pathway in non-physiological shear stress-induced platelet activation.

The PI3K/Akt signaling pathway has been implicated in playing an important role in platelet activation during hemostasis and thrombosis involving platelet-matrix interaction and platelet aggregation. Its role in non-physiological shear stress (NPSS)-induced platelet activation relevant to high-shear blood contacting medical devices (BCMDs) is unclear. In the context of blood cells flowing in BCMDs, platelets are subjected to NPSS (>100 Pa) with very short exposure time (<1 s). In this study, we investigated whether NPSS with short exposure time induces platelet activation through the PI3K/Akt signaling pathway. Healthy donor blood treated with or without PI3K inhibitor was subjected to NPSS (150 Pa) with short exposure time (0.5 s). Platelet activation indicated by the surface P-selectin expression and activated glycoprotein (GP) IIb/IIIa was quantified using flow cytometry. The phosphorylation of Akt, activation of the PI3K signaling, was characterized by western blotting. Changes in adhesion behavior of NPSS-sheared platelets on fibrinogen, collagen, and von Willebrand factor (vWF) were quantified with fluorescent microscopy by perfusing the NPSS-sheared and PI3K inhibitor-treated blood through fibrinogen, collagen, and vWF-coated microcapillary tubes. The results showed that the PI3K/Akt signaling was involved with both NPSS-induced platelet activation and platelet-matrix interaction. NPSS-sheared platelets exhibited exacerbated platelet adhesion on fibrinogen, but had diminished platelet adhesion on collagen and vWF. The inhibition of PI3K signaling reduced P-selectin expression and GPIIb/IIIa activation with suppressed Akt phosphorylation and abolished NPSS-enhanced platelet adhesion on fibrinogen in NPSS-sheared blood. The inhibition of PI3K signaling can attenuate the adhesion of unsheared platelets (baseline) on collagen and vWF, while had no impact on adhesion of NPSS-sheared platelets on collagen and vWF. This study confirmed the important role of PI3K/Akt signaling pathway in NPSS-induced platelet activation. The finding of this study suggests that blocking PI3K/Akt signaling pathway could be a potential method to treat thrombosis in patients implanted with BCMDs.

Evaluation of in vitro hemolysis and platelet activation of a newly developed maglev LVAD and two clinically used LVADs with human blood.

In vitro hemolysis testing remains one of the most important performance measures to judge the hemocompatibility of a left ventricular assist device (LVAD). Clinically relevant operating conditions and appropriate testing blood are essential to infer in vitro data for potential clinical use. This in vitro study was carried out to evaluate and compare the hemolytic performance of a newly developed magnetically levitated (maglev) LVAD (CH-VAD) with two clinically used LVADs (HVAD and HeartMate II (HMII)) using fresh human blood. A small volume (~300 mL) in vitro circulating flow loop was constructed with a LVAD generated flow of 4.5 L/min at the nominal or reported clinical operating speed for each LVAD. The blood was circulated in the loop for 4 hours with samples drawn at baseline and hourly. Plasma-free hemoglobin (PFH) concentrations in the hourly blood samples were determined with spectrophotometry. Normalized index of hemolysis (NIH) was calculated to compare the hemolytic performance of the CH-VAD and the two reference LVADs. Platelet activation was measured with flow cytometry. The experimental test for each device was repeated at least 7 times. The data from this study showed that all the three LVADs generated very low hemolysis (NIH <0.01 g/100 L). The CH-VAD was found to have a significantly lower NIH value (0.00135 ± 0.00032 g/100 L) compared to the HVAD (0.00525 ± 0.00183 g/100 L) and the HMII (0.00583 ± 0.00182 g/100 L). No statistically significant difference in device-generated hemolysis was found between the HVAD and the HMII. The level of platelet activation induced by the CH-VAD is significantly lower than those by the HVAD and the HMII. The data suggest that the shear-induced hemolysis and platelet activation of the CH-VAD are acceptable relative to the two LVADs currently in clinical use.

A novel adaptor system enables endovascular access through extracorporeal life support circuits.

OBJECTIVE: Extracorporeal life support has traditionally been used as a supportive platform for patients with cardiopulmonary failure. Many of these patients require endovascular access for the performance of diagnostic or therapeutic procedures, and obtaining vascular access in these patients can be problematic. We sought to develop a novel system that allows the extracorporeal life support circuit to serve as an access point to the cardiovascular system. METHODS: By using computer-aided design, modeling, and 3-dimensional printing, a novel adaptor that can be easily inserted and removed from an extracorporeal life support circuit was developed. A mock loop was used to measure flow and pressure at various pump speeds with insertion of guidewires and catheters through the adaptor. The ability of the system to enable performance of endovascular procedures in vivo was then tested in a porcine extracorporeal life support model. RESULTS: By using a small arterial cannula (15F) at 3500 RPM and 3.2 LPM, 15% and 24% decrements in circuit flow were observed when a 0.035" guidewire and 5F angiography catheter, respectively, were passed through the adaptor (P < .001). However, when using a larger arterial cannula (23F) at 3500 RPM and 4.7 LPM, only 3% and 5% decrements in flow were observed (P < .001), respectively, with intermediate changes when using 17F to 21F cannulas. In vivo testing confirmed that this system enables the performance of a variety of endovascular procedures, including left ventriculography, aortic root and coronary angiography, and descending aortography. CONCLUSIONS: This novel system successfully enables endovascular access through an extracorporeal life support circuit. This technology may transform extracorporeal life support from a purely supportive strategy to a platform for endovascular intervention.