Intraoperative Management of an Orthotopic Porcine-to-Human Cardiac Xenotransplant.

We report the intraoperative management of an orthotopic cardiac xenotransplant in a 57-year-old man with nonischemic cardiomyopathy requiring venoarterial extracorporeal membrane oxygenation. Transesophageal echocardiography was used for preharvest assessment. Continuous ex vivo perfusion of the heart was performed. Steps were taken to avoid potential xenozoonosis transmission to other patients and staff. Preclinical experience guided our intraoperative management in controlling hemodynamics and using prophylactic antiarrhythmic medications. Echocardiography aided in the diagnosis of aortic dissection in the patient after transplant. Intraoperative cardiac function was excellent. The patient was weaned from all mechanical support 4 days after transplant.

Intraoperative echocardiographic assessment of mitral valve translocation.

OBJECTIVES: The aim of this study was to present a rigorous method to analyse the intraoperative echocardiographic images from the novel mitral translocation procedure, which assesses the changes in mitral structure and function and compares this data to a control group of patients who have no mitral regurgitation (MR). METHODS: Transoesophageal echocardiography was post-processed using dedicated 3D software. Ten patients with normal mitral valves (MV) undergoing non-mitral cardiac surgery served as controls. Mitral coaptation area, mid-leaflet coaptation length and mitral annular circumference were measured in 3D. RESULTS: Twenty-three consecutive patients with severe secondary MR underwent MV translocation. All patients had none/trace MR post-translocation. The mean coaptation surface area increased from 63 to 427 mm2 (P < 0.001) and coaptation length increased from 1.0 to 10.5 mm (P < 0.001). The control group coaptation surface area (136 mm2) and length (2.5 mm) were greater than pre-translocation (P = 0.019; P < 0.001) and less than post-translocation (P < 0.001; P < 0.001). 3D mitral annular circumference in the translocation group decreased 15% (130-110 mm) (P < 0.001). Post-translocation, the mean gradient was 2(2-3) mmHg with the diastolic mitral orifice area of 3.4 ± 0.3 cm2 by planimetry and 3.5 ± 0.3 cm2 by pressure half-time. The coaptation to septum distance remained unchanged (P = 0.305) without systolic anterior leaflet motion. CONCLUSIONS: This echocardiographic analysis method demonstrates that MV translocation abolishes secondary MR, increases coaptation area and length and produces acceptable diastolic function. This method of analysis should allow precise structural and quantitative assessment of the durability of the repair in future long-term follow-up.

A Pharmacokinetic and Plasmin-Generation Pharmacodynamic Assessment of a Tranexamic Acid Regimen Designed for Cardiac Surgery With Cardiopulmonary Bypass.

OBJECTIVES: To examine the pharmacokinetics (PK) and pharmacodynamics of a tranexamic (TXA) regimen designed for cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: A pilot study quantifying TXA concentrations, fibrinolysis markers, and a plasmin- generation (PG) assay. For comparison, PG assay was performed on pooled normal plasma (PNP) with varying TXA concentrations. SETTING: A single-center, tertiary, academic medical center. PARTICIPANTS: Twenty patients undergoing cardiac surgery with CPB for valve surgery and/or coronary artery bypass grafting. INTERVENTION: TXA 100 mg/h infusion for 5 hours starting before incision; 1 g TXA in CPB prime and 1 g TXA at CPB end prior to heparin reversal. MEASUREMENTS AND MAIN RESULTS: The PK fit a 2-compartment disposition model. TXA concentrations were above 15 mg/L in all patients during CPB through 2 hours post-TXA infusion. During and after CPB, the TXA regimen decreased the median peak PG by 60% (95% confidence interval [CI], 56%-62%). Lowest median peak PG occurred 15 minutes postprotamine. Peak median D-dimer level of 1.24 (0.95-1.71; 95% CI) mg/L occurred at 15 minutes postprotamine and baseline-adjusted ΔD dimer correlated with increased CPB time (p = 0.004) and lower TXA level (p = 0.001). The median 24-hour chest tube output was 447 (330-664; 95% CI) mL. PG assay on PNP revealed a plateau inhibition at 5 mM TXA (786 mg/L). CONCLUSIONS: This regimen, with total perioperative dose of 2.5 grams, provided TXA concentrations above 15 mg/L for all patients from CPB initiation through 2 hours post-TXA. PG was significantly inhibited (p < 0.0001) during and after CPB, with maximum inhibition measured at 15 minutes after protamine administration.

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.

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.

Hematologic evaluation of intraoperative autologous blood collection and allogeneic transfusion in cardiac surgery.

BACKGROUND: Acute normovolemic hemodilution is recommended as a technique to reduce allogeneic red blood cell (RBC) transfusions in cardiac surgery, but its efficacy to reduce non-RBC transfusion has not been consistently demonstrated. We hypothesized that intraoperative large-volume autologous whole blood (AWB) collection and reinfusion improves viscoelastic coagulation parameters. STUDY DESIGN AND METHODS: Prospective observational study of cardiac surgery patients at the University of Maryland Medical Center between December 2017 and August 2019. Rotational thromboelastometry parameters were compared between AWB and control groups (n = 25 in each group) at three time points: T1, baseline; T2, on cardiopulmonary bypass (CPB) after the cross-clamp removal; and T3, 30-60 minutes after protamine administration. The study's primary outcomes were whole blood viscoelastic coagulation parameters that included EXTEM clotting time (CT), FIBTEM amplitude at 10 minutes, and EXTEM amplitude at 10 minutes (EXTEM-A10 ). Chest tube drainage and allogeneic transfusion were secondary outcomes. RESULTS: Reinfusion of AWB after CPB resulted in a significantly shorter EXTEM CT; mean difference, -11.4 seconds (-21.4 to -1.4; P = .03). It also resulted in a greater percentage increase in EXTEM A10 from T2 to T3; mean difference, 7.8% (95% CI, 1.1%-14.5%; P = .02). Statistical significance was not found in 24-hour chest tube drainage. CONCLUSION: Large-volume AWB collection and reinfusion are feasible in selected cardiac surgical patients, and may be associated with prohemostatic effects according to thromboelastometry, warranting further investigation with a prospective randomized study.

A Pharmacokinetic and Pharmacodynamic Investigation of an ε-Aminocaproic Acid Regimen Designed for Cardiac Surgery With Cardiopulmonary Bypass.

OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of an ε-aminocaproic acid (EACA) regimen designed for cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: Prospective observational study requiring blood sampling to measure EACA concentrations and fibrinolysis markers (fibrinogen, D-dimer, α2-antiplasmin, and tissue plasminogen activator-plasminogen activator inhibitor [tPA-PAI-1] complex). SETTING: Single-center, tertiary medical center. PARTICIPANTS: Patients who underwent cardiac surgery with CPB between 2018 and 2019 for aortic or mitral valve replacement/repair or coronary artery bypass grafting. Previous sternotomy patients were included. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of EACA, during CPB, were described by a 3-compartment disposition model. EACA concentrations were greater than 130 mg/L in all patients after CPB and in most patients during CPB. The D-dimer level trended up and reached a peak median level of 1.35 mg/L of fibrinogen equivalence units (FEU) at 15 minutes after protamine administration. The median change in D-dimer (ΔD-dimer) from baseline to 15 minutes after protamine was 0.34 (-0.48 to 3.81) mg/L FEU. ΔD-dimer did not correlate with EACA concentration intraoperatively, urine output, body weight, glomerular filtration rate, cell salvage volume, and ultrafiltration volume. The median 24-hour chest tube output was 445 (180-1,011) mL. CONCLUSION: This regimen provided maximum EACA concentrations near the time of protamine administration, with a total perioperative dose of 15 g. Most patients had EACA concentrations greater than the target during CPB. ΔD-dimer did not correlate with EACA concentration. The median 24-hour chest tube output compared well to similar studies that used higher doses of EACA.

Evolution of viscoelastic coagulation testing.

INTRODUCTION: The methods of viscoelastic coagulation testing (VCT) have evolved since the original invention of thrombelastography over 60 years ago, and new generations of devices are clinically used to guide hemostatic interventions at bedside. The utility of VCTs has been demonstrated in several clinical trials, but diagnostic performance of VCT may vary between devices, various transfusion algorithms, and patient populations. AREAS COVERED: Working principles and currently available data on the evolving VCTs for coagulation monitoring in acute care settings are reviewed. The PubMed database was used to search pertinent retrospective, prospective, and meta-analysis data on VCTs. EXPERT OPINION: Point-of-care VCTs provide clinically useful information on platelet count, fibrin polymerization, and other procoagulant factor activities in acute bleeding due to trauma or major surgery, and antithrombotic therapy. The addition of fibrin-specific VCT channel has brought renewed attention to early correction of fibrinogen deficiency using fibrinogen-rich component therapy, and stabilization of fibrin with antifibrinolytic agents. Normal reference ranges vary between devices, and diagnostic and treatment algorithms should be specifically established for each device and indication. There is interest in utilizing VCTs in complex coagulation management relating to hemophilia with inhibitors, but the standardized protocol has not been established.

Clotting Time Results Are Not Interchangeable Between EXTEM and FIBTEM on Rotational Thromboelastometry.

OBJECTIVE: To explore how cytochalasin D (CyD) affects clot initiation and to compare clotting times (CTs) of EXTEM and FIBTEM on rotational thromboelastometry in cardiac surgical patients undergoing cardiopulmonary bypass (CPB). DESIGN: Retrospective cohort study with translational in vitro coagulation experiments. SETTING: Single-center, tertiary, academic medical center. PARTICIPANTS: Patients who underwent cardiac surgery with CPB between November 2015 and August 2017. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The study's primary measurements were CTEXTEM and CTFIBTEM before and after CPB. Additionally, the authors performed translational in vitro coagulation experiments using commercial plasma. In these experiments, the impact of CyD on in vitro thrombin generation (TG) was assessed using 10 platelet-rich plasma (PRP) samples and calibrated automated thrombogram. The impact of CyD on ROTEM-CT also was evaluated in vitro using the same 10 PRP samples. One hundred fifty-three patients had clinical CTEXTEM and CTFIBTEM measurements. CTFIBTEM was shorter than CTEXTEM before and after CPB by 6.8% (95% confidence interval [CI], 5.5-8.1) and 8.9% (95% CI, 4.7-13.0), respectively. These results correlated with in vitro experiments, where TG lag time was shortened by CyD and CTFIBTEM was shorter than CTEXTEM. CONCLUSION: CyD shortens the onset of TG and clot formation, resulting in shorter CTFIBTEM than CTEXTEM. The authors' data suggest that CTEXTEM and CTFIBTEM are not interchangeable. Additional clinical studies are warranted to assess if CTFIBTEM can be used to optimize the indication for plasma transfusion.

Perioperative Management of Patients With Hereditary Angioedema With Special Considerations for Cardiopulmonary Bypass.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder mostly due to the deficiency of C1-esterase inhibitor (C1-INH). Reduced C1-INH activity below ~38% disrupts homeostasis of bradykinin (BK) formation by increasing kallikrein activation and causes recurrent angioedema attacks affecting the face, extremities, genitals, bowels, oropharynx, and larynx. HAE symptoms can be debilitating and potentially life-threatening. The recent clinical developments of biological and pharmacological agents have immensely improved acute and long-term care of patients with moderate-to-severe HAE. The therapies are given as on-demand and/or prophylaxis, and self-administration is highly recommended and performed with some agents via intravenous or subcutaneous route. Perioperative clinicians need to be familiar with the symptoms and diagnosis of HAE as well as available therapies because of the potential need for airway management, sedation, or anesthesia for various medical and surgical procedures and postoperative care. Cardiovascular surgery using cardiopulmonary bypass is a unique condition in which heparinized blood comes into direct contact with an artificial surface while pulmonary circulation, a major reserve of angiotensin-converting enzyme (ACE), becomes excluded. These changes result in systemic kallikrein activation and BK formation even in non-HAE patients. The objectives of this review are (1) to review pathophysiology of HAE and laboratory testing, (2) to summarize pertinent pharmacological data on the prophylactic and on-demand treatment strategies, and (3) to discuss available clinical data for perioperative management in cardiovascular surgery.

Impact of intraoperative high-volume autologous blood collection on allogeneic transfusion during and after cardiac surgery: a propensity score matched analysis.

BACKGROUND: Perioperative use of allogeneic blood products is associated with higher morbidity, mortality, and hospital costs after cardiac surgery. Blood conservation techniques such as acute normovolemic hemodilution (ANH) report variable success. We hypothesized that large-volume ANH with limited hemodilution would reduce allogeneic blood transfusion compared to the standard practice. STUDY DESIGN AND METHODS: Retrospective observational study of cardiac surgery patients at the University of Maryland Medical Center between January 2014 and September 2017. Using the institutional Society of Thoracic Surgeons database 91 autologous and 981 control patients who underwent coronary artery bypass grafting, aortic valve replacement, or both were identified. After propensity matching of 13 preoperative characteristics, 84 autologous and 84 control patients were evaluated. Our primary endpoint was avoidance of blood transfusion during index hospitalization, and secondary endpoints were postoperative bleeding and major adverse outcomes. RESULTS: The median harvest volumes in the ANH and control groups were 1100 mL and 400 mL, respectively. Of the ANH group, 25% received any transfusion versus 45.2% of the control group after propensity score matching (p < 0.006). When controlling for preoperative platelet count, the transfusion rate ratios for ANH were 0.58 (95% confidence interval, 0.39-0.88) for RBCs and 0.63 (0.44-0.89) for non-RBC components, which were both found to be statistically significant. There was no difference found in major adverse events. CONCLUSION: These results suggest that large-volume ANH is beneficial in reducing both RBC and non-RBC component usage in cardiac surgery. A further prospective validation is warranted.

Clinical Impact of Protamine Titration-Based Heparin Neutralization in Patients Undergoing Coronary Bypass Grafting Surgery.

OBJECTIVES: A hemostasis management system (HMS) is a point-of-care method for heparin and protamine titration. The authors hypothesized that protamine dosing over the HMS estimate would be associated with elevated activated clotting time (ACT), increased bleeding, and transfusion owing to protamine's anticoagulant activity. DESIGN: A retrospective cohort study. SETTING: Single-center university hospital. PARTICIPANTS: One hundred eighty-nine patients undergoing elective coronary artery bypass grafting surgery. INTERVENTIONS: Patients were stratified into 3 groups per ratio of actual total administered protamine versus the HMS-derived protamine estimate: (1) low-ratio (≤66% of HMS estimate), (2) moderate-ratio (66%-100% of HMS estimate), and (3) high-ratio (>100% of HMS estimate). MEASUREMENTS AND MAIN RESULTS: The primary endpoints were post-protamine ACT, and residual heparin levels on HMS among the 3 groups in addition to bleeding and transfusion. There were 54 (28.6%) patients in the low, 95 (50.3%) in the moderate, and 40 (21.2%) in the high-ratio group. The high-ratio patients who were overdosed with protamine relative to the HMS estimate had elevated ACT, international normalized ratio, and activated partial thromboplastin time values, and subsequently received more red blood cell (RBC) and non-RBC transfusions compared to lower-ratio groups. Higher actual/HMS protamine ratios were associated independently with post-protamine ACT elevations after adjustment for sex, body mass index (BMI), and cardiopulmonary bypass (CPB) time. CONCLUSION: Most patients received the protamine dose sufficiently close to the HMS estimate, but protamine dosing above the HMS estimate occurred in both obese and nonobese patients, which was associated independently with prolonged ACT after adjusting for sex, BMI, and CPB time.

Computational simulation and comparison of prothrombin complex concentrate dosing schemes for warfarin reversal in cardiac surgery.

BACKGROUND: Prothrombin complex concentrate (PCC) is increasingly used for acute warfarin reversal. We hypothesized that computational modeling of thrombin generation (TG) could be used to optimize the timing and dose of PCC during hemodilution induced by cardiopulmonary bypass (CPB). METHODS: Thrombin generation patterns were modeled in anticoagulated patients (n = 59) using a published computational model. Four dosing schemes were evaluated including single full dose (median, 41.2 IU/kg) of PCC before or after CPB, ½-dose before and after CPB, or 1/3-dose before CPB plus 2/3-dose after CPB. Hemodilution was modeled as 40 or 60 % dilution of factors from baseline. The lag time (s) of TG, and peak thrombin level (nM) were evaluated. RESULTS: Prolonged lag time, and reduced peak TG were due to low vitamin K-dependent (VKD) factors, and pre-CPB PCC dose-dependently restored TG to near-normal or normal range. After 40 % dilution, TG parameters were similar among 4 regimens at the end of therapy. The recovery of VKD factors was less when PCC was given before CPB after 60 % dilution, but TG parameters were considered hemostatically effective (>200 nM) with any regimen. Withholding the full dose of PCC until post-CPB resulted in severely depressed TG peak (median, 47 nM) after 60 % dilution, and some supra-normal TG peaks after treatment. CONCLUSIONS: Pre-CPB administration of full or divided doses of PCC prevents extremely low TG peak during surgery, and maintains hemostatic TG peaks in both 40 and 60 % hemodilution models. Although PCC's hemostatic activity appears to be highest using the full dose after CPB, hypercoagulability may develop in some cases.