Transcatheter aortic valve replacement in low-risk young population:A double edge sword?

Since the advent of transcatheter aortic valve replacement(TAVR)in 2002,it has now become the default interventional strategy for symptomatic patients presenting with severe aortic stenosis,particularly in intermediate to highsurgical risk patients.In 2019,the United States Food and Drug Administration approved TAVR in low-risk patients based on two randomized trials.However,these breakthrough trials excluded patients with certain unfavorable anatomies and odd profiles.While currently there is no randomized study of TAVR in young patients,it may be preferred by the young population given the benefits of early discharge,shorter hospital stay,and expedite recovery.Nonetheless,it is important to ruminate various factors including lifetime expectancy,risk of pacemaker implantation,and the need for future valve or coronary interventions in young cohorts before considering TAVR in these patients.Furthermore,the data on long-term durability(>10 years)of TAVR is still unknown given most of the procedures were initially performed in the high or prohibitive surgical risk population.Thus,this editorial aims to highlight the importance of considering an individualized approach in young patients with consideration of various factors including lifetime expectancy while choosing TAVR against surgical aortic valve replacement.

Current knowledge for the risk factors of early permanent pacemaker implantation following transcatheter aortic valve replacement and what is next for the primary prevention?

In this editorial,we comprehensively summarized the preoperative risk factors of early permanent pacemaker implantation after transcatheter aortic valve replacement(TAVR)among patients with severe aortic stenosis from several renowned clinical studies and focused on the primary prevention of managing the modifiable factors,e.g.,paroxysmal atrial fibrillation before the TAVR.

Psychological Status and Warfarin Therapy in Patients after Valve Replacement during the COVID-19 Pandemic:A Cross-sectional Study

Objective The standardization of warfarin anticoagulant therapy is the key to lifelong treatment for patients after heart valve replacement.The present study explored the possible risk factors for anxiety and depression during the coronavirus disease 2019(COVID-19)pandemic and analyzed the influence of psychological state on medication safety.Methods Eligible patients received a web-based questionnaire survey via the Wenjuanxing platform during outpatient visits.Depression was evaluated by the Self-Rating Depression Scale(SDS).Anxiety was evaluated by the Self-Rating Anxiety Scale(SAS).Medication adherence was evaluated by the Morisky scale.Results A total of 309 patients(aged 52.2±11.4 years)were included in the present study.The SDS score of all included patients was 36.9±9.4 points,of which 11(3.6%)patients were diagnosed as having depression.The SAS score of all included patients was 43.1±9.3 points,of which 71(23%)patients were diagnosed as having anxiety.Seven patients(2.3%)had both anxiety and depression.Logistic regression analysis revealed that only monthly income was an independent influencing factor for depression.Regarding anxiety,patients who underwent repeated operations had a 2.264-fold greater risk,and patients who received combination medication had a 2.140-fold greater risk.More bleeding events and coagulation disorders could be observed in patients with anxiety,depression or both.When anxiety occurred,patients showed worse medication adherence.However,depression had no significant effect on medication adherence.Conclusion During the COVID-19 pandemic,the detection rate of mental illnesses such as anxiety and depression was high,which seriously affected the medication safety of warfarin.Analysis of its influencing factors will provide a reference for further standardized regulation of warfarin anticoagulant therapy after valve replacement.

Rates, predictors, and causes of readmission after transcatheter aortic valve replacement in patients with chronic kidney disease

BACKGROUND Transcatheter aortic valve replacement(TAVR)is a revolutionary procedure for severe aortic stenosis.The coexistence of chronic kidney disease(CKD)and TAVR introduces a challenge that significantly impacts patient outcomes.AIM To define readmission rates,predictors,and causes after TAVR procedure in CKD stage 1-4 patients.METHODS We used the national readmission database 2018 and 2020 to look into readmission rates,causes and predictors after TAVR procedure in patients with CKD stage 1-4.RESULTS Out of 24758 who underwent TAVR and had CKD,7892(32.4%)patients were readmitted within 90 days,and had higher adjusted odds of being females(adjusted odds ratio:1.17,95%CI:1.02-1.31,P=0.02)with longer length of hospital stay>6 days,and more comorbidities including but not limited to diabetes mellitus,anemia,and congestive heart failure(CHF).CONCLUSION Most common causes of readmission included CHF(18.0%),sepsis,and complete atrioventricular block.Controlling readmission predictors with very close followup is warranted to prevent such high rate of readmission.

Risk of permanent pacemaker implantation following transcatheter aortic valve replacement:Which factors are most relevant?

Transcatheter aortic valve replacement(TAVR)has emerged as a formidable treatment option for severe symptomatic aortic stenosis ahead of surgical aortic valve replacement.The encouraging results from large randomized controlled trials has resulted in an exponential rise in the use of TAVR even in the low-risk patients.However,this is not without challenges.Need for permanent pacemaker(PPM)post-TAVR remains the most frequent and clinically relevant challenge.Naturally,identifying risk factors which predispose an individual to develop high grade conduction block post-TAVR is important.Various demographic factors,electrocardiographic features,anatomic factors and procedural characteristics have all been linked to the development of advanced conduction block and need for PPM following TAVR.Amongst these electrophysiological variables,most notably a prolonged QRS>120 ms regardless of the type of conduction block seems to be one of the strongest predictors on logistic regression models.The index study by Nwaedozie et al highlights that patients requiring PPM post-TAVR had higher odds of having a baseline QRS>120 ms and were more likely to be having diabetes mellitus that those who did not require PPM.

Pacemaker post transcatheter aortic valve replacement:A multifactorial risk?

Pacemaker post-transcatheter aortic valve replacement is related to multifactorial risk.Nwaedozie et al brought to the body of evidence electrocardiogram and clinical findings.However,procedural characteristics have at least as much impact on the final need for a permanent pacemaker and potentially on the pacing rate.In this regard,long-term follow-up and understanding of the impact of long-term stimulation is of utmost importance.

Prognostic Role of Preoperative Tricuspid Annular Plane Systolic Excursion (TAPSE) in Mitral Valve Replacement (MVR) for Rheumatic Mitral Stenosis Patients

Tricuspid annular plane systolic excursion has been proposed as a simple and reproducible parameter for quantitative assessment of the right ventricular ejection fraction. The prognostic importance of preoperative TAPSE in patients with mitral valve replacement for rheumatic mitral stenosis patients is still under focused. Therefore, the objective of the study was to predict the outcome after MVR in rheumatic mitral stenosis patients in relation to preoperative TAPSE. This comparative cross-sectional study was conducted at the Department of Cardiac Surgery, National Heart Foundation Hospital and Research Institute. A total of 72 patients of rheumatic mitral stenosis patients who underwent mitral valve replacement were included in the study. They were divided into two groups: Group A and B. Group A included 36 patients with TAPSE 0.05) except for the preoperative TAPSE. Mean TAPSE of Group A was 13.17 (±1.40) and Group B was 18.61 (±1.57), the difference was statistically significant (p 0.05). Among the postoperative complications, including postoperative atrial fibrillation was higher in Group A (30.56%) than Group B (11.11%), mean ventilation time was higher in Group A (27.78%) than Group B (5.56%), length of intensive care was higher in Group A (33.33%) than Group B (11.12%), and hospital stay was higher in Group A (25.0%) than Group B (5.56%), (p < 0.05). Higher preoperative TASPE could be used as a prognostic tool for MVR in rheumatic mitral stenosis patients in our settings.

Comparison Study of Different Drainage Tube Diameters with Negative Pressure Suction after Valve Replacement Surgery

Objective: This study aims to compare the effects of different drainage tube diameters (22F vs. 26F) combined with negative pressure suction on patients after valve replacement surgery, including postoperative indicators and complications. Methods: A total of 104 patients undergoing valve replacement surgery were included and divided into a 22F group (45 patients) and a 26F group (59 patients). The basic characteristics, postoperative ICU stay duration, drainage duration, postoperative complications, and pain scores were compared between the two groups. All data were analyzed using SPSS statistical software, with p Results: There were no significant differences between the two groups in terms of age, sex, and underlying diseases. The ICU stay duration and drainage duration showed no significant differences (p > 0.05). The total drainage volume in the 22F group was significantly lower than that in the 26F group (225 vs. 380 ml, p = 0.035), and the pain scores on the third postoperative day were also significantly lower in the 22F group (p Conclusion: Compared to the 26F group, patients in the 22F group exhibited less postoperative drainage volume and lower pain scores, suggesting that the 22F drainage tube may have better clinical outcomes after valve replacement surgery.

Transcatheter versus surgical aortic valve replacement in severe, symptomatic aortic stenosis

Aortic stenosis （AS） is the most common type of valvular heart disease in the elderly. Surgical aortic valve replacement （SAVR） has been the standard practice for treating severe, symptomatic AS, but recently new treatment options have emerged, Transcatheter aortic valve replacement （TAVR） is now an established treatment option in patients at high surgical risk. In this review, we focus on recent developments and compare the two treatment methods in specific populations in terms of efficacy and safety （e.g., in patients with history of prior thoracic surgery, type of anesthesia employed, access site used or need for permanent pacing）. The impact of comorbidities （pulmonary hypertension, arterial hypertension and obesity paradox）, the cost-effectiveness of TAVR vs. SAVR and advances in transcatheter valve technology as well as issues that merit further investigation are further discussed. Moreover, outcomes and complications of TAVR in patients of different risk category （extremely high, high, intermediate and low risk） are analyzed. We strongly believe that during the following years, TAVR may evolve as the treatment of choice in a broader group of patients with symptomatic AS and beyond those with intermediate and high-risk features.

Long-Term Outcome and Risk Factor Analysis of Surgical Pulmonary Valve Replacement in Congenital Heart Disease

Objectives:To establish long-term outcome of surgical pulmonary valve replacement(PVR)in congenital heart disease(CHD)and to identify risk factors for overall mortality,operative mortality,and repetitive PVR.Methods:This is a retrospective study of 375 surgical PVR in 293 patients who underwent surgical PVR for CHD between January 2000 and May 2020.We only included patients with index PVR with previous open-heart surgery regardless of the number of PVRs.The previous surgical history of patients who underwent PVR during the study period was also included.Patients who underwent the Rastelli operation,and those who underwent single PVR without previous open-heart surgery were excluded.Results:The median age of the patients at the time of surgical PVR was 14.9 years(Interquartile range,IQR,11.0–22.0).The median follow-up duration was 10.5 years(IQR,5.5–14.8 years).There were 3 patients with operative mortality(1.0%)and 15 patients with overall mortality(5.1%).The survival rate was 95.1%over 20 years follow-up period.Multivariate analysis demonstrated that more than 3 times of previous open-heart surgeries before surgical PVR,older age at the first operation,longer cardiopulmonary bypass(CPB)time and longer intensive care unit(ICU)stay were predictors for overall mortality.Patients who underwent surgical PVR after more than 3 times of previous open-heart surgeries had significantly higher mortality than those who underwent open-heart surgeries less than 3 times(P<0.001).Age younger than 10 years,male,multiple valve problems and longer ICU stay were significant predictors for repetitive PVR by multivariate analysis.Conclusions:Though surgical PVR has excellent long-term outcome,it should be performed with caution for those who previously underwent multiple open-heart surgeries,especially if patient received more than 3 times of open-heart surgeries.

Feasibility and clinical outcomes in nonagenarians undergoing transcatheter aortic valve replacement with the LOTUSTM valve

Surgical aortic valve replacement （AVR） is associated with very high peri-operative risk in the nonagenarian populationflI Patients with severe aortic stenosis treated conservatively have high rates of mortality with poor quality of life and loss of independence. Transcatheter aortic valve replacement （TAVR） has been validated in the high risk elderly population as a viable alternative to surgery with comparable outcomes.

Transcatheter aortic valve replacement and stroke： a comprehensive review

Transcatheter aortic valve implantation （TAVR） has emerged as an alternative, rapidly evolving treatment option for patients with se- vere aortic stenosis and high surgical risk. Stroke is a devastating complication being confined mainly in the periprocedural and 30-day pe- riod following TAVR, with a lower and relatively constant frequency thereafter. Early stroke is mainly due to debris embolization during the procedure, whereas later events are associated with patient specific factors. Despite the fact that the rate of clinical stroke has been constantly decreasing compared to initial TAVR experience, modern neuro-imaging with MRI suggests that new ischemic lesions post-TAVR are almost universal. The impact of the latter is largely unknown. However, they seem to correlate with a reduction in neurocognitive function. Because TAVR is set to expand its indication to lower surgical-risk patients, stroke prophylaxis during and after TAVR becomes of paramount importance. Based on clinical and pathophysiological evidence, three lines of research are actively employed towards this direction： improvement in valve and delivery system technology with an aim to reduce manipulations and contact with the calcified aortic arch and native valve, antithrombotic therapy, and embolic protection devices. Careful patient selection, design of the procedure, and tailored antithrombotic strategies respecting the bleeding risks of this fragile population constitute the main defense against stroke following TAVR.

Combined Low-dose Aspirin and Warfarin Anticoagulant Therapy of Postoperative Atrial Fibrillation Following Mechanical Heart Valve Replacement

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients （620 females, mean age of 36.8-4-7.7 years） admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study （warfarin plus 75-100 mg aspirin） or control （warfarin only） groups. International normalized ratio （INR） and prothrombin time were main- tained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respec- tively （P〉0.05）. The incidence of overall thromboembolic events in study group was lower than that in control group （2.16% vs. 4.35%, P=0.049）. No statistically significant differences were found in hem- orrhage events （3.53% vs. 3.95%, P=-0.722） or mortality （0.20% vs. 0.40%, P=0.559） between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

Novel predictors of permanent pacemaker implantation following transcatheter aortic valve replacement

BACKGROUND Conduction and rhythm abnormalities requiring permanent pacemakers(PPM)are short-term complications following transcatheter aortic valve replacement(TAVR),and their clinical outcomes remain conflicting.Potential novel predictors of post-TAVR PPM,like QRS duration,QTc prolongation,and supraventricular arrhythmias,have been poorly studied.AIM To evaluate the effects of baseline nonspecific interventricular conduction delay and supraventricular arrhythmia on post-TAVR PPM requirement and determine the impact of PPM implantation on clinical outcomes.METHODS RESULTS Out of the 357 patients that met inclusion criteria,the mean age was 80 years,188(52.7%)were male,and 57(16%)had a PPM implantation.Baseline demographics,valve type,and cardiovascular risk factors were similar except for type II diabetes mellitus(DM),which was more prevalent in the PPM cohort(59.6%vs 40.7%;P=0.009).The PPM cohort had a significantly higher rate of pre-procedure right bundle branch block,prolonged QRS>120 ms,prolonged QTc>470 ms,and supraventricular arrhythmias.There was a consistently significant increase in the odds ratio(OR)of PPM implantation for every 20 ms increase in the QRS duration above 100 ms:QRS 101-120[OR:2.44;confidence intervals(CI):1.14-5.25;P=0.022],QRS 121-140(OR:3.25;CI:1.32-7.98;P=0.010),QRS 141-160(OR:6.98;CI:3.10-15.61;P<0.001).After model adjustment for baseline risk factors,the OR remained significant for type II DM(aOR:2.16;CI:1.18-3.94;P=0.012),QRS>120(aOR:2.18;CI:1.02-4.66;P=0.045)and marginally significant for supraventricular arrhythmias(aOR:1.82;CI:0.97-3.42;P=0.062).The PPM cohort had a higher adjusted OR of heart failure(HF)hospitalization(aOR:2.2;CI:1.1-4.3;P=0.022)and nonfatal myocardial infarction(MI)(aOR:3.9;CI:1.1-14;P=0.031)without any difference in mortality(aOR:1.1;CI:0.5-2.7;P=0.796)at one year.CONCLUSION Pre-TAVR type II DM and QRS duration>120,regardless of the presence of bundle branch blocks,are predictors of post-TAVR PPM.At 1-year post-TAVR,patients with PPM have higher odds of HF hospitalization and MI.

Bioprosthetic Valve Size Selection to Optimize Aortic Valve ReplacementSurgical Outcome: A Fluid-Structure Interaction Modeling Study

Aortic valve replacement(AVR)remains a major treatment option for patients with severe aortic valve disease.Clinical outcome of AVR is strongly dependent on implanted prosthetic valve size.Fluid-structure interaction(FSI)aortic root models were constructed to investigate the effect of valve size on hemodynamics of the implanted bioprosthetic valve and optimize the outcome of AVR surgery.FSI models with 4 sizes of bioprosthetic valves(19(No.19),21(No.21),23(No.23)and 25 mm(No.25))were constructed.Left ventricle outflow track flow data from one patient was collected and used as model flow conditions.Anisotropic Mooney–Rivlin models were used to describe mechanical properties of aortic valve leaflets.Blood flow pressure,velocity,systolic valve orifice pressure gradient(SVOPG),systolic cross-valve pressure difference(SCVPD),geometric orifice area,and flow shear stresses from the four valve models were compared.Our results indicated that larger valves led to lower transvalvular pressure gradient,which is linked to better post AVR outcome.Peak SVOPG,mean SCVPD and maximum velocity for Valve No.25 were 48.17%,49.3%,and 44.60%lower than that from Valve No.19,respectively.Geometric orifice area from Valve No.25 was 52.03%higher than that from Valve No.19(1.87 cm2 vs.1.23 cm2).Implantation of larger valves can significantly reduce mean flow shear stress on valve leaflets.Our initial results suggested that larger valve size may lead to improved hemodynamic performance and valve cardiac function post AVR.More patient studies are needed to validate our findings.

Echocardiographic Monitoring of Cardiac Parameters after Mitral Valve Replacement with the Preservation of Subvalvular Structures

To date many monitoring techniques have been used to determine the efficacy of surgical correction of mitral valve disease. The most common non-invasive method in use is echocardiography which can assess the myocardial and mitral valve function changes after mitral valve replacement procedures. In this study, we investigated the five-year follow-up echocardiographic results of 143 patients undergoing mitral valve replacement with preservation of subvalvular apparatus to analyze the recovery of myocardial and mitral valve functions.

Transcatheter aortic valve replacement in elderly patients

Aortic stenosis is the most common native valve disease, affecting up to 5% of the elderly population. Surgical aortic valve replacement reduces symptoms and improves survival, and is the definitive therapy in patients with symptomatic severe aortic stenosis. However, despite the good results of classic surgery, risk is markedly increased in elderly patients with co-morbidities. Transcatheter aortic valve replacement （TAVR） allows implantation of a prosthetic heart valve within the diseased native aortic valve without the need for open heart surgery and cardiopulmonary bypass, offering a new therapeutic option to elderly patients considered at high surgical risk or with contraindications to surgery. To date, several multicenter registries and a randomized trial have confirmed the safety and efficacy of TAVR in those patients. In this chapter, we review the background and clinical applications of TAVR in elderly patients.

Comparison of in-hospital outcomes between octogenarians and nonagenarians undergoing transcatheter aortic valve replacement： a propensity matched analysis

Background Aortic valve stenosis （AS） is very common in the elderly patients above 80 years. Transcatheter aortic valve replacement （TAVR） in such patients is being increasingly performed. This study sought to assess in-hospital outcome differences between octogenarians and nonagenarians and predictors of mortality in nonagenarians undergoing TAVR with severe AS. Method The study population was derived from the National Inpatient Sample （MS） for the years 2012-2014 using ICD-9 CM procedure codes 35.05 and 35.06 for TAVR. Hospitalizations below 80 years of age were excluded. After performing propensity score matching （1： 2）, in-hospital outcomes were compared in matched cohorts. Then, multivariate model was developed to analyze predictors of in-hospital mortality in nonagenarians. Results There were 11,630 hospitalizations in the octogenarian and 5815 hospitalizations in the nonagenarian group. Primary outcome of in-hospital mortality （6% vs. 4.1%, P ≤ 0.001） was higher in nonagenarians compared to octogenarians. Secondary outcomes including stroke （3.4% vs. 2.8%, P ≤ 0.001）, renal failure （18.9% vs. 17.3%, P ≤0.001）, blood transfusion （35% vs. 32.6%, P ≤ 0.001）, vascular complications （4.5% vs. 3.5%, P ≤ 0.001）, and pacemaker implantation （27.8% vs. 24.8%, P ≤ 0.001） were higher in nonagenarians. There was no difference in their length of stay. Median cost （70,3745 vs. 65,3815, P ≤ 0.001） was slightly higher with nonagenarian. Conclusions Although in-hospital mortality is slightly higher in nonagenarians, it is acceptable. This difference in mortality is at least partly explained by higher complications in nonagenarians. Efforts should be made to decrease the complications which can further narrow the difference in in-hospital mortality between the groups.

Effect of transcatheter aortic valve replacement on P-wave duration, P-wave dispersion and left atrial size

Background P-wave dispersion （PWD）, a measure of heterogeneity of atrial refractoriness, is defined as the difference between the maximum and minimum P-wave duration. In patients with severe aortic stenosis （AS）, P-wave duration and PWD were shown to be increased, indicating atrial electrical remodeling. However, the effect of transcatheter aortic valve replacement （TAVR） on P-wave morphology has not been established yet. The aim of this study is to assess the short and long-term effects of TAVR with two types of bioprosthetic valves on P-wave duration and PWD in association with left atrial （LA） size. Methods Fifty-two （36 female） eligible patients in sinus rhythm who underwent transfemoral TAVR between June 01, 2012 and July 31, 2014 with either a Medtronic CoreValve （MCV） （n = 32） or an Edwards SAPIEN XT Valve （n = 20） were enrolled. Standard 12-lead electrocardiogram and echocardiographic evaluations were per- formed pre-procedurally, post-TAVR day one and 6 months post-TAVR. P-wave duration and PWD were measured and correlation analyses with echocardiographic variables were performed. Results P-wave duration and PWD were significantly decreased on post-TAVR day one （P 〈 0.05）. They continued to decrease during the six month follow-up period, but were not significantly different from short-term values （P 〉 0.05）. The decrease of LA diameter was found significant at the sixth-months of follow-up （P 〈 0.05）. These changes were independent from the types of bioprosthetic valves implanted （P 〉 0.05）. A positive correlation was detected between minimum P-wave duration and maximum aortic valve gradients at post-TAVR day one （r = 0.297, P = 0.032）. Conclusions P-wave duration and PWD were significantly reduced early after TAVR indicating early reverse atrial electrical remodeling. Moreover, structural reverse remodeling of atrium was detected at the 6-months of follow-up. The effects of two types of bioprosthetic valves on atrial remodeling were similar.

Anticoagulation early after mechanical heart valve replacement

Objective： To explore the changes of coagulation activity and the characters of anticoagulation early after mechanical heart valve replacement. Methods： All patients only took warfarin orally for anticoagulation. The predicted international normalized ratio （INR） was 1.5 to 2.0. Several coagulation markers were monitored early after valve replacement. Complications associated with anticoagulation were recorded and analyzed. The patients were divided into three groups based on the number and position of mechanical valve prothesis, including group M （mitral valve replacement）, group A （aortic valve replacement） and group D （mitral and aortic valve replacement）.Comparison was made between the three groups. Results： Three events of mild cerebral embolism and five events of mild bleeding occurred during the early postoperative period. One patient suffered from mild cerebral embolism on the 4th day after operation, accompanied by large volume of pericardial drainage. Two patients with bleeding had lower INRs than predicted range. However, INR in one patient with mild cerebral embolism was in the predicted range. There was no significant difference in thrombo time （TT）, activated partial thromboplastin time （APTT） and 1NR on the 3rd day after operation compared to those before operation; meanwhile, plasma fibrinogen （FIB） concentration was higher than that before operation （P〈0.05）. 1NR had no significant changes on the 2nd day after the beginning of anticoagulation compared to that before operation; however, 1NR was significantly elevated on the 4th day （P〈0.05）. Warfarin doses and INRs were similar among the three groups, but FIB concentrations in plasma were higher in groups M and D than in group A （P〈0.01）. Conclusion： Hypercoagulabale state exists early after mechanical heart valve replacement. When anticoagulation begins is determined by the change of coagulation markers, not by the volume of chest or pericardial drainage. INR can not accurately reflect the coagulation state sometimes, especially during the first 3 days after anticoagulation. The number and position of mechanical valve prothesis could affect coagulation state. Therefore, anticoagulation therapy should be regulated accordingly.