In vitro effects of emicizumab on activated clotting time in blood samples from cardiac surgical patients.

BACKGROUND: Heparin management in hemophilia A (HA) patients with a factor VIII (FVIII) inhibitor can be challenging due to severe activated clotting time (ACT) prolongations. It is important to better understand the impact of emicizumab, a FVIII mimetic on ACT, and tissue factor (TF)-based coagulation assays. METHODS: Whole blood from 18 patients undergoing cardiopulmonary bypass (CPB) were mixed in vitro with pooled normal plasma, FVIII-deficient or FVIII-inhibitor plasma to affect functional FVIII levels. ACTs and heparin concentration by protamine titration were measured in whole blood mixture with/without emicizumab (50-100 µg/ml). Thrombin generation and plasmin generation were measured in the patient's plasma mixed with normal plasma or FVIII-inhibitor plasma to assess the impact of emicizumab under low TF activation. RESULTS: FVIII inhibitors prolonged ACTs by 2.2-fold compared to those in normal plasma mixture at baseline. During CPB, ACTs in normal plasma mixture, and FVIII-deficient mixture were in 400s, but ACTs reached 900s in FVIII-inhibitor mixture. Emicizumab shortened ACTs by up to 100s in normal plasma mixture, and FVIII-deficient mixtures. ACTs remained over 600s in FVIII-inhibitor mixture, despite adding emicizumab at 100 µg/ml. Heparin concentration measured by TF-based protamine titration was unaffected. Emicizumab enhanced thrombin peak in the presence of FVIII inhibitors, whereas plasmin generation was mainly affected by thrombin generation, and systemic use of ɛ-aminocaproic acid. CONCLUSIONS: FVIII inhibitors extensively prolong ACTs in heparinized whole blood, and clinical levels of emicizumab partially reverse ACT values. Protamine titration should be considered for optimal heparin monitoring in emicizumab-treated patients with FVIII inhibitors.

Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months.

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

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.

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.

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.

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.

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.

Coagulation Factor Levels and Underlying Thrombin Generation Patterns in Adult Extracorporeal Membrane Oxygenation Patients.

BACKGROUND: There is a paucity of data on the underlying procoagulant-anticoagulant balance during extracorporeal membrane oxygenation (ECMO). We hypothesized that adult ECMO patients would have an imbalance between procoagulant and anticoagulant factors, leading to an abnormal underlying thrombin generation (TG) pattern. METHODS: Twenty adult venoarterial (VA) ECMO patients had procoagulant and anticoagulant factor levels measured temporally on ECMO day 1 or 2, day 3, and day 5. In heparin-neutralized plasma, underlying TG patterns, and sensitivity to activated protein C were assessed using calibrated automated thrombogram. TG parameters including lag time, peak TG, and endogenous thrombin potential (ETP) were compared against 5 normal plasma controls (3 males and 2 females) obtained from a commercial supplier. Thrombomodulin (TM) was added to some samples to evaluate for activated protein C resistance. RESULTS: Procoagulant factors (factor [F] II, FV, and FX) were mostly in normal reference ranges and gradually increased during the first 5 ECMO days (P = .022, <.001, <.001). FVIII levels were elevated at all time points and did not change (P = .766). In contrast, FXI was in the low-normal range but did not increase during ECMO (P = .093). Antithrombin (AT) and protein C levels were below normal but increased during the first 5 ECMO days (P = .002 and P = .014). Heparinase-treated samples showed prolonged lag time, increased peak TG, and increased ETP compared to controls; mean difference in lag time on ECMO day 1 or 2 = 6.0 minutes (99% confidence interval [CI], 2.8-9.2), peak TG = 193.4 (99% CI, 122.5-264.3), and ETP = 1170.4 (99% CI, 723.2-1617.6). After in vitro TM treatment, differences in TG parameters were accentuated and ECMO samples appeared insensitive to TM treatment; mean difference in lag time on ECMO day 1 or 2 = 9.3 minutes (99% CI, 6.2-12.4), peak TG = 233.0 (99% CI, 140.9-325.1), and ETP = 1322.5 (99% CI, 764.8-1880.2). Similar differences in TG parameters were observed on ECMO days 3 and 5. CONCLUSIONS: Contact activation occurs during ECMO, but procoagulant factor levels are generally preserved. Although heparin-neutralized TG is delayed, peak TG and ETP are supranormal in the setting of high FVIII and low AT and protein C levels. Resistance to TM is also apparent. These changes demonstrate a possible mechanism for hypercoagulability during adult VA ECMO.

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.

Intra-abdominal Hypertension and Postoperative Kidney Dysfunction in Cardiac Surgery Patients.

OBJECTIVE: To determine the incidence of intra-abdominal hypertension (IAH) in adult cardiac surgery patients and its association with postoperative kidney dysfunction. DESIGN: Prospective cohort study. SETTING: Single tertiary-care university hospital. PARTICIPANTS: Forty-two adult patients having cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Intra-abdominal pressure (IAP) was measured preoperatively, immediately after surgery, and at the following time points after surgery: 3 hours, 6 hours, 12 hours, and 24 hours. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels were measured as a marker of kidney dysfunction at the following time points: prior to surgery, immediately after surgery, 4 to 6 hours after surgery, and 16-to-18 hours after surgery. MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-two IAPs were measured, and 90 (35.7%) showed IAH. Thirty-five of 42 patients (83.3%) had IAH at 1 time point or more. Peak urine NGAL levels were lower in patients with normal IAP (mean difference = -130.6 ng/mL [95% CI = -211.2 to -50.1], p = 0.002). There was no difference in postoperative kidney dysfunction by risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) criteria in patients with normal IAP (mean difference = -31.4% [95% CI = -48.0 to 6.3], p = 0.09). IAH was 100% sensitive for predicting postoperative kidney dysfunction by RIFLE criteria, but had poor specificity (54.8%). CONCLUSIONS: IAH occurs frequently during the perioperative period in cardiac surgery patients and may be associated with postoperative kidney dysfunction.

Effect of cardiopulmonary bypass on platelet mitochondrial respiration and correlation with aggregation and bleeding: a pilot study.

BACKGROUND: Cardiopulmonary bypass (CPB) may cause platelet dysfunction, contributing to bleeding. There are no investigations of how CPB affects platelet mitochondrial respiration and what correlation this has with platelet aggregation and bleeding. METHODS: We studied platelet mitochondrial respiration and aggregation in eighteen adult cardiac surgery patients having CPB. The relationships between respiration, aggregation and postoperative bleeding were analyzed. RESULTS: Platelet respiration, reflected by the respiratory control ratio (RCR), was unchanged after CPB (mean difference in RCR= -0.02 (95% CI=-1.45 to 1.42), p=0.98). Further, there were no significant relationships between indexed adenosine diphosphate (ADP) or thrombin receptor-activating peptide (TRAP)-induced aggregation and the RCR (p=0.12 and p=0.41). Only post-CPB ADP - induced aggregation correlated with 24-hr chest tube output (p=0.04), but indexing for platelet count attenuated the effect (p=0.07). CONCLUSION: Platelet mitochondrial respiration is preserved after CPB and is not correlated with aggregation or bleeding. Only post-CPB, ADP-induced aggregation correlates with postoperative bleeding.

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.

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.

Ethical considerations during a pioneering surgical procedure: porcine cardiac xenotransplantation.

Preclinical advances in life-sustaining porcine cardiac xenotransplantation from donor pigs to baboons have paved the way for the performance of porcine cardiac xenotransplantation in a human. This procedure was performed with emergency use authorisation granted by the United States Food and Drug Administration under the umbrella of investigational new drug use on compassionate grounds. The patient was denied candidacy for durable mechanical circulatory support and heart transplantation as a result of non-adherence to medical advice. Successful porcine cardiac xenotransplantation in humans will significantly increase the availability of potential donor organs for long-term management of end-stage heart failure. Human porcine cardiac xenotransplantation is associated with ethical conflicts encompassing multiple ethical principles which are not mutually exclusive and are sometimes conflicting. This article focuses on some of the ethical conflicts encountered in relation to the use of mechanical circulatory support, pretransplant evaluation, shared decision making during informed consent, infectious disease risk, preclinical and clinical testing, and the role of regulatory bodies during performance of the first human porcine cardiac xenotransplantation. An increase in human trials of xenotransplantation procedures is imminent. Potential ethical conflicts associated with xenotransplantation should be addressed appropriately.

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.