Mechanical Prosthetic Heart Valves Research Articles

Thromboembolism in pregnancy: Challenges and controversies in the prevention of pregnancy-associated venous thromboembolism and management of anticoagulation in women with mechanical prosthetic heart valves

Thromboembolism in pregnancy is an important clinical issue. Despite identification of maternal and pregnancy-specific risk factors for development of pregnancy-associated venous thromboembolism, limited data are available to inform on optimal approaches for prevention. The relatively low overall prevalence of pregnancy-associated venous thromboembolism has prompted debate about the validity of recommendations, which are mainly based on expert opinion, and have resulted in an increased use of pharmacological thromboprophylaxis in pregnancy and postpartum. A pragmatic approach is required in the absence of more robust data. Anticoagulation management of pregnant women with mechanical prosthetic heart valves is particularly challenging. Continuation of therapeutic anticoagulation during pregnancy is essential to prevent valve thrombosis. Warfarin, the most effective anticoagulant, is associated with adverse fetal outcomes, including embryopathy and stillbirth. Fetal outcome is improved with therapeutic-dose low-molecular-weight heparin, but there may be more thromboembolic complications. More intensive anticoagulation, targeting higher trough anti-Xa levels, may reduce the risk of valve thrombosis.

Monitoring of Anti-Xa in Pregnant Patients With Mechanical Prosthetic Valves Receiving Low-Molecular-Weight Heparin

We hypothesized that the guideline-recommended peak anti-Xa levels for pregnant women with mechanical prosthetic heart valves (MPHVs) receiving adjusted dose low-molecular-weight heparin (LMWH) are associated with subtherapeutic trough levels and consequently with an inadequate level of anticoagulation. Low-molecular-weight heparin is often used for anticoagulation in pregnant women including those with MPHV. American College of Cardiology/American Heart Association guidelines recommend monitoring of plasma anti-Xa factor peak levels and adjustment of the dose to achieve peak levels of 0.7 to 1.2 U/mL. In spite of these recommendations, cases of valve thrombosis during pregnancy continue to occur. We studied 30 pregnant patients receiving anticoagulation for various indications with adjusted dose LMWH given subcutaneously twice a day which had both trough and peak anti-Xa levels throughout pregnancy for a total of 187 paired determinations. The recommended peak anti-Xa levels (0.7-1.2 U/mL) were obtained in 123 (66%) of the measurements but in 80% of them, the trough levels were found to be subtherapeutic (<0.6 U/mL). Subtherapeutic trough levels were found in 8 (73%) of the 11 measurements with peak levels of 0.7 to 0.79 U/mL, 17 (74%) of the 23 of 0.8 to 0.89 U/mL, 21 (72%) of the 29 of 0.9 to 0.99 U/mL, and 28 (44%) of the 63 of 1.0 to 1.2 U/mL. There were 42 measurements with peak anti-Xa levels >1.2 U/mL and even in these cases, 13 (31%) of the trough levels were found to be subtherapeutic. Anticoagulation with adjusted dose LMWH aimed to achieve guideline-recommended peak levels of anti-Xa for patients with MPHVs is commonly associated with subtherapeutic trough levels. Routine measurement of trough anti-Xa levels is therefore advisable in women with MPHV treated with LMWH during pregnancy to assure adequate level of anticoagulation.

The impact of a new model-based iterative reconstruction algorithm on prosthetic heart valve related artifacts at reduced radiation dose MDCT

To assess the impact of hybrid iterative reconstruction (IR) and novel model-based iterative reconstruction (IMR) and dose reduction on prosthetic heart valve (PHV) related artifacts and objective image quality. One transcatheter and two mechanical PHVs were embedded in diluted contrast-gel, inserted in an anthropomorphic phantom and imaged stationary with retrospectively ECG-gated computed tomography. Eight acquisitions were obtained of each PHV at 120kV, 600mAs (routine), 300 and 150mAs (reduced dose). Data were reconstructed with filtered back projection (FBP), IR and IMR. Hypodense and hyperdense artifact volumes were quantified using two threshold filters. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated. Artifact volumes differed significantly between reconstruction algorithms for all PHVs (P<0.005). Compared to FBP, IR decreased overall hypodense and hyperdense artifact volumes; at 150mAs by 53 and 20% (IR) and 67 and 23% (IMR), respectively and significantly increased SNR and CNR at all doses (P<0.012). Even at reduced dose, IMR resulted in higher image quality than routine dose FBP and IR. Iterative reconstruction and particularly IMR significantly reduce PHV-related artifacts and improve objective image quality in non-pulsatile conditions, even in reduced-dose images. Also, this study suggests that IMR allows for more radiation dose reduction in comparison to hybrid IR while maintaining high image quality.

Warfarin and atrial fibrillation: from ideal to real the warfarin affaire

Vitamin K Antagonists (VKAs) are widely used in clinical practice and nearly 1% of the entire population receives oral anticoagulation at least once in life. However, the rate of prescription of anticoagulation is low, compared to what it should be. No more than 50-60% of patients affected by atrial fibrillation (AF) receive anticoagulation. In the setting of AF, VKAs are safe and effective when properly managed, reducing stroke and systemic embolism by more than 60%. VKAs safety and effectiveness are closely related to the quality of anticoagulation (e.g. time in therapeutic range), and anticoagulation clinics offer the best management of anticoagulant therapy. However, a sizeable proportion of patients are managed elsewhere. In clinical practice, in the setting of AF, a low prescription rate of VKAs is frequently observed and this is due also to difficulties in managing laboratory monitoring and drug dose adjustment. The suboptimal management of therapy with VKAs leads to a lesser efficacy than that reported in clinical trials, and to an increase in adverse reactions. VKAs still remain the first and only available therapy for a number of diseases (e.g. valvular atrial fibrillation and mechanical prosthetic heart valves). Now, since approval of the new oral anticoagulants (NOAs), the choice of anticoagulant therapy in definite settings, such as stroke prevention in non-valvular atrial fibrillation (SPAF) or treatment of venous thromboembolism, has surely become more intriguing but also more problematic. In light of these new therapeutic options, we reviewed VKAs therapy, in the setting of atrial fibrillation, focusing on VKAs impact in real life. We analyzed the data about efficacy and safety of warfarin at three levels: clinical trial and real life, outside and inside anticoagulation clinics.

Unanswered questions and research priorities to optimise stroke prevention in atrial fibrillation with the new oral anticoagulants

This review article discusses the following, as yet unanswered, questions and research priorities to optimise patient management and stroke prevention in atrial fibrillation with the new direct oral anticoagulants (NOACs): 1. In patients prescribed a NOAC, can the anticoagulant effects or plasma concentrations of the NOACs be measured rapidly and reliably and, if so, can "cut-off points" between which anticoagulation is therapeutic (i.e. the "therapeutic range") be defined? 2. In patients who are taking a NOAC and bleeding (e.g. intracerebral haemorrhage), can the anticoagulant effects of the direct NOACs be reversed rapidly and, if so, can NOAC-associated bleeding and complications be minimised and patient outcome improved? 3. In patients taking a NOAC who experience an acute ischaemic stroke, to what degree of anticoagulation or plasma concentration of NOAC, if any, can thrombolysis be administered safely and effectively? 4. In patients with a recent cardioembolic ischaemic stroke, what is the optimal time to start (or re-start) anticoagulation with a NOAC (or warfarin)? 5. In anticoagulated patients who experience an intracranial haemorrhage, can anticoagulation with a NOAC be re-started safely and effectively, and if so when? 6. Are the NOACs effective and safe in multimorbid geriatric people (who commonly have atrial fibrillation and are at high risk of stroke but also bleeding)? 7. Can dose-adjusted NOAC therapy augment the established safety and efficacy of fixed-dose unmonitored NOAC therapy? 8. Is there a dose or dosing regimen for each NOAC that is as effective and safe as adjusted-dose warfarin for patients with atrial fibrillation who have mechanical prosthetic heart valves? 9. What is the long-term safety of the NOACs?

Multidetector-Row Computed Tomography Allows Accurate Measurement of Mechanical Prosthetic Heart Valve Leaflet Closing Angles Compared With Fluoroscopy

The purpose of this study was to compare multidetector-row computed tomography (MDCT) leaflet restriction measurements with fluoroscopy measurements in commonly used mechanical prosthetic heart valves (PHVs). Four mechanical PHVs (ON-X, Carbomedics, St. Jude, and Medtronic Hall) were imaged in a pulsatile model using fluoroscopy and 64-detector-row computed tomography. Five image acquisitions of each PHV without (1) and with (4) restricted leaflet closure were made. Three observers measured closure angles on fluoroscopy and MDCT. Data were analyzed using intraclass correlation coefficient (ICC) and Bland-Altman plots. Interobserver agreement was high in restricted and non-restricted leaflets on both modalities (ICCs >0.995). MDCT and fluoroscopy showed high agreements (ICCs >0.989). Median MDCT closure angle measurements differed at most -2 to +2 degrees from fluoroscopy in the restricted and -1 to +2 degrees in the non-restricted leaflets. MDCT allows measurement of leaflet motion with a maximal median discrepancy of 2 degrees. Both MDCT and fluoroscopy detect restricted leaflet closure with great accuracy.

Oral Anticoagulation after Mechanical Heart Valve Replacement: Low Intensity Regimen can Make the Difference

Despite continuous improvement in the field, the ideal prosthetic heart valve remains to be developed. Patients with mechanical prosthetic heart valves are at risk of thrombosis and systemic embolism. The incidence rate of these serious complications is significantly reduced by lifelong Oral Anticoagulant Therapy (OAC) vitamin K antagonist (VKA) therapy. Despite its undeniable benefits, VKA therapy with warfarin is affected by a number of known limitations, including bleeding complications, dietary and drug interactions, and need for international normalized ratio (INR) monitoring and dose adjustments. In particular, the optimal intensity of anticoagulant therapy remains a delicate equilibrium and continues to be an ongoing matter of debate. A significant number of trials has been published on this topic. In this review article we review the pathogenesis of OAC related complications, the evidences supporting current recommendations along with the results of major prospective randomised trials on low intensity OAC regimens and self-management. Safe and effective chronic OAC therapy after mechanical valve replacement requires a thorough examination of patients’ features, optimal surgical techniques, state of the art definition of target INR levels and close surveillance. Based on our and other work, we argue that low-dose anticoagulation is safe and feasible in selected mechanical valve recipients and also it may be of benefit during pregnancy. Concurrently, evidence from most recent reports highlights that even higher risk patients’ subsets may profit from low intensity protocols. These data postulate that low intensity regimen of OAC coupled with close INR monitoring can make a significant difference for low to intermediate risk patients with aortic mechanical valve replacement.

Alternative causes of bioreaction to prosthetic heart valves: three cases with pannus formation

Pannus formation is an infrequent but serious complication of prosthetic heart valve surgery. The cause of pannus is recognized as a bioreaction to the prostheses; histological investigations have shown that pannus comprises collagen and elastic tissues containing endothelial cells, chronic inflammatory cells, and myofibroblasts. However, the detailed mechanism of its formation has not been fully demonstrated. We aimed to evaluate the potential role of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in the pathogenesis of pannus formation in three patients with mechanical prosthetic heart valves. Pannus specimens removed from the prostheses were fixed in 10% neutral-buffered formalin for 24 hours after surgical removal and paraffin-embedded using standard procedures. Serial sections were cut at 4 µm for immunohistochemistry analysis. Hematoxylin and eosin (HE) was used in the histological analysis. VEGF and MMP-2 were studied in the immunohistochemistry analysis. Three patients with mechanical prosthetic obstruction due to pannus overgrowth underwent redo valve surgery. In the first and second patients, the mitral prosthesis was explanted along with the pannus overgrowth. The third patient had both aortic and mitral prostheses; the aortic prosthesis was explanted with obstructive pannus formation, whereas the mitral valve was spared with excision of the nonobstructive pannus. The immunohistochemical study demonstrated the expressions of MMP-2 and VEGF in all of the pannus specimens acquired from these cases. VEGF and MMP-2 may play a role in the mechanism of pannus formation as the elements of the chronic active inflammatory process.

Thrombus attached to suture materials successfully thrombolysed with low-dose tissue plasminogen activator

Mechanical prosthetic heart valve thrombosis is one of the most common complications of valve surgery. We herein describe an unusual clinical vignette. A 60-year-old man who underwent prosthetic mitral valve reoperation suffered from nonobstructive thrombus attached to the elongated suture materials in the postoperative sixth month. The thrombus was precisely depicted by two- and three-dimensional transesophageal echocardiography and was successfully lysed with low-dose slow infusion of tissue plasminogen activator after failed heparin treatment.

Outcomes and total costs of outpatient vs. inpatient peri-procedural anticoagulation management of mechanical prosthetic heart valve patients

Background/objectivesThe most cost-effective periprocedural management of patients with mechanical heart valves (MHV) is uncertain. The objective was to compare the effectiveness, safety and costs for inpatient intravenous unfractionated heparin (IVUH) vs. outpatient low molecular weight heparin (LMWH) “bridging” as periprocedural anticoagulation management for MHV patients. MethodsIn a case-cohort study, Olmsted County, MN residents with MHV who received outpatient periprocedural LMWH management (cases) over the 11-year period, 1997–2007, were matched to residents with MHV who received inpatient IVUH periprocedural management on valve location and type, and on procedure type. Patients were followed for 3months following hospitalization to identify thromboembolism (TE) and major bleeding. Total costs from 30days before to 90days after the procedure were determined from the Olmsted County Healthcare Expenditure and Utilization Database. Outcomes were compared using survival analysis and costs were compared using the Wilcoxon rank sum. Results149 cases (100 aortic, 29 mitral, 20 both; 64% bileaflet) were compared to 149 cohort members (100 aortic, 29 mitral, 20 both; 75% bileaflet). While the 3-month cumulative incidence of TE did not differ significantly among cases (2.7%) and cohort members (4.7%; p=0.36), major bleeding was significantly lower in cases (5.4% vs. 15.4%; p<0.005). Total costs were significantly higher for cohort members ($50,984 vs. $39,347; p=0.002) due to higher inpatient costs ($47,729 vs. $34,860; p=0.0002). ConclusionsOutpatient bridging LMWH therapy is equally effective, but safer and less costly than inpatient IVUH as periprocedural anticoagulation management for MHV patients.

Risks and pregnancy outcome in women with prosthetic mechanical heart valve: our experience

Risks and pregnancy outcome in women with prosthetic mechanical heart valve: our experience

Differentiation of thrombus from pannus as the cause of acquired mechanical prosthetic heart valve obstruction by non-invasive imaging: a review of the literature

For acquired mechanical prosthetic heart valve (PHV) obstruction and suspicion on thrombosis, recently updated European Society of Cardiology guidelines advocate the confirmation of thrombus by transthoracic echocardiography, transesophageal echocardiography (TEE), and fluoroscopy. However, no evidence-based diagnostic algorithm is available for correct thrombus detection, although this is clinically important as fibrinolysis is contraindicated in non-thrombotic obstruction (isolated pannus). Here, we performed a review of the literature in order to propose a diagnostic algorithm. We performed a systematic search in Pubmed and Embase. Included publications were assessed on methodological quality based on the validated Quality Assessment of Diagnostic Accuracy Studies (QUADAS) II checklist. Studies were scarce (n = 15) and the majority were of moderate methodological quality. In total, 238 mechanical PHV's with acquired obstruction and a reliable reference standard were included for the evaluation of the role of fluoroscopy, echocardiography, or multidetector-row computed tomography (MDCT). In acquired PHV obstruction caused by thrombosis, mass detection by TEE and leaflet restriction detected by fluoroscopy were observed in the majority of cases (96 and 100%, respectively). In contrast, in acquired PHV obstruction free of thrombosis (pannus), leaflet restriction detected by fluoroscopy was absent in some cases (17%) and mass detection by TEE was absent in the majority of cases (66%). In case of mass detection by TEE, predictors for obstructive thrombus masses (compared with pannus masses) were leaflet restriction, soft echo density, and increased mass length. In situations of inconclusive echocardiography, MDCT may correctly detect pannus/thrombus based on the morphological aspects and localization. In acquired mechanical PHV obstruction without leaflet restriction and absent mass on TEE, obstructive PHV thrombosis cannot be confirmed and consequently, fibrinolysis is not advised. Based on the literature search and our opinion, a diagnostic algorithm is provided to correctly identify non-thrombotic PHV obstruction, which is highly relevant in daily clinical practice.

Prosthetic mechanic valve thrombosis in pregnancy: a single center study of 7 cases

Background: Pregnancy in women with mechanical prosthetic heart valves carried an increased risk of thromboembolic complications due to changes in haemostasis. Prosthetic valve thrombosis is a serious complication resulting in high mortality. We reviewed the incidence, risk factors, and treatment strategies of this rare complication. Methods: In the present study 86 pregnancies in 57 women with prosthetic mechanical heart valve replacement were identified in our institution between 1985 and 2011. After careful review of the records, the most likely preditors of prosthetic valve thrombosis was assigned. Results: Seven patients from 23 to 38 years of age (mean age was 30 years) had 7 thromboses of mechanical heart prostheses during pregnancy. The prosthesis was mitral in all cases. The prosthesis was a ball valve in 3 cases and bi-leaflet in 4 cases. The most frequent clinical presentation was severe congestive heart failure. Initial emergency treatment was surgical in 3 cases and medical in 4 cases (simple heparin therapy). Secondary surgery was carried out in one patient after failure of heparin therapy. There was one death in the surgical group and 33% foetal mortality in the surviving women. In univariate analysis, predictors of prosthetic valve thrombosis were: inadequate level of anticoagulation and dilation of the left atrium Conclusion: Thrombosis is the most life-threatening complication for women with prosthetic heart valve during pregnancy. Inadequate level of anticoagulation and dilation of the left atrium are the two factors involved in the pathogenesis of prosthetic valve thrombosis. The overall mortality rate despite surgical treatment remains high. This study underscores the importance of meticulous surveillance of anticoagulation therapy in pregnant women with prosthetic valves.

China-made CL-V bileaflet mechanical heart valve: a clinical application of 21 cases

Objective To introduce a new type of China-made bileaflet mechanical prosthetic heart valve(CL-V bileaflet valve)and evaluate its early clinical effectiveness and short-term follow-up outcomes.Methods Twenty-one patients were included in the present study,with 18 receiving mitral valve replacement and 3 receiving combined mitral and aortic replacement.One AST bileaflet valve(imported) and 23 CL-V bileaflet valves were implanted(21 in mitral position,including one 25M and 20 27M;and 2 in aortic position,including one 23A and one 25A).The ventricular and atrial volume,cardiac function,hemodynamics and hemocompatibility were compared before and one week,6 months after operation.Valve-related complications were observed during perioperative period and follow-up.Results All the patients were followed up for 6-61 months,with a mean of 19.8 months.There was no early mortality( 30 d after operation).The patients had stable hemodynamics and satisfactory hemocompatibility early after operation and during short-term follow-up;there were no valve-related complications.Conclusion The early clinical results and short-term follow-up outcomes of CL-V bileaflet prosthetic valve are satisfactory,with no valve-related complications.The long-term outcome of CL-V bileaflet prosthetic valve needs to be further observed.

Toward optimization of a novel trileaflet polymeric prosthetic heart valve via device thrombogenicity emulation.

Aortic stenosis is the most prevalent and life-threatening form of valvular heart disease. It is primarily treated via open-heart surgical valve replacement with either a tissue or a mechanical prosthetic heart valve (PHV), each prone to degradation and thrombosis, respectively. Polymeric PHVs may be optimized to eliminate these complications, and they may be more suitable for the new transcatheter aortic valve replacement procedure and in devices like the total artificial heart. However, the development of polymer PHVs has been hampered by persistent in vivo calcification, degradation, and thrombosis. To address these issues, we have developed a novel surgically implantable polymer PHV composed of a new thermoset polyolefin called cross-linked poly(styrene-block-isobutylene-block-styrene), or xSIBS, in which key parameters were optimized for superior functionality via our device thrombogenicity emulation methodology. In this parametric study, we compared our homogeneous optimized polcymer PHV to a prior composite polymer PHV and to a benchmark tissue valve. Our results show significantly improved hemodynamics and reduced thrombogenicity in the optimized polymer PHV compared to the other valves. These results indicate that our new design may not require anticoagulants and may be more durable than its predecessor, and validate the improvement, toward optimization, of this novel polymeric PHV design.

Management of Patients With Atrial Fibrillation (Compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS Recommendations)

This document is a compilation of the current American College of Cardiology Foundation/American Heart Association (ACCF/AHA) practice guideline recommendations for atrial fibrillation (AF) from the “ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation),”* the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline)”† and the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran).”‡ Updated and new recommendations from 2011 are noted and outdated recommendations have been removed. No new evidence was reviewed, and no recommendations included herein are original to this document. The ACCF/AHA Task Force on Practice Guidelines chooses to republish the recommendations in this format to provide the complete set of practice guideline recommendations in a single resource. ### 1.1. Pharmacological and Nonpharmacological Therapeutic Options #### 1.1.1. Rate Control During AF Class I 1. Measurement of the heart rate at rest and control of the rate using …

P-007 Pregnant women with mechanical prosthetic heart valves – Which anticoagulant is best?

P-007 Pregnant women with mechanical prosthetic heart valves – Which anticoagulant is best?

Anticoagulant choices in pregnant women with mechanical heart valves: Balancing maternal and fetal risks – the difference the dose makes

Long-term anticoagulation is required in all patients with mechanical prosthetic heart valves to prevent complications with valve thrombosis and valve failure or systemic thromboembolism. The prothrombotic environment of pregnancy further increases the risks of these complications. Anticoagulant choices for pregnant women include oral vitamin K antagonists such as warfarin, or heparin – either unfractionated heparin (UFH) or low molecular weight heparin (LMWH). None of the options is without risk for the mother or her baby. Warfarin crosses the placenta and is associated with warfarin embryopathy and fetopathy but is very effective at preventing thromboembolic complications. The dose of warfarin may play a role in the risk of some, but not all fetal complications. Heparin does not cross the placenta but is less effective at preventing thrombosis and LMWH may be more effective than UFH. The optimal dose and target anti-Xa levels for LMWH have not been established. Measurement of trough anti-Xa levels in addition to peak anti-Xa levels may be important.

Classification of mechanical prosthetic heart valve sounds

Heart sounds of patients are usually used for analysis by cardiologists for the purpose of early detection of various heart diseases. In this paper, Hilbert-Huang transform HHT is applied to analyse five different kinds of mechanical prosthetic heart valve sounds, and an HHT-based feature extraction procedure is also developed to classify these five different mechanical heart valve sounds.

CT attenuation measurements are valuable to discriminate pledgets used in prosthetic heart valve implantation from paravalvular leakage

Sutures with polytetrafluorethylene (PTFE) felt pledgets are commonly used in prosthetic heart valve (PHV) implantation. Paravalvular leakage can be difficult to distinguish from PTFE felt pledgets on multislice CT because both present as hyperdense structures. We assessed whether pledgets can be discriminated from contrast-enhanced solutions (blood/saline) on CT images based on attenuation difference in an ex vivo experiment and under in vivo conditions. PTFE felt pledgets were sutured to the suture ring of a mechanical PHV and porcine aortic annulus, and immersed and scanned in four different contrast-enhanced (Ultravist®; 300 mg jopromide ml(-1)) saline concentrations (10.0, 12.0, 13.6 and 15.0 mg ml(-1)). Scanning was performed on a 256-slice scanner with eight different scan protocols with various tube voltage (100 kV, 120 kV) and tube current (400 mAs, 600 mAs, 800 mAs, 1000 mAs) settings. Attenuation of the pledgets and surrounding contrast-enhanced saline were measured. Additionally, the attenuation of pledgets and contrast-enhanced blood was measured on electrocardiography (ECG)-gated CTA scans of 19 patients with 22 PHVs. Ex vivo CT attenuation differences between the pledgets and contrast-enhanced solutions were larger by using higher tube voltages. CT attenuation values of the pledgets were higher than contrast-enhanced blood in patients: 420±26 Hounsfield units (mean±SD, range 383-494) and 288±41 Hounsfield units (range 202-367), respectively. PTFE felt pledgets have consistently higher attenuation than surrounding contrast-enhanced blood. CT attenuation measurements therefore may help to differentiate pledgets from paravalvular leakage, and detect paravalvular leakage in patients with suspected PHV dysfunction.