Mechanical Cardiac Valves Research Articles

Pleiotropic Effects of Heparin and its Monitoring in the Clinical Practice.

Unfractionated heparin (UFH) was uncovered in 1916, has been used as an anticoagulant since 1935, and has been listed in the World Health Organization's Model List of Essential Medicines. Despite the availability of many other anticoagulants, the use of heparin (either low molecular weight heparin [LMWH] or UFH) is still substantial. Heparin has pleotropic effects including anticoagulant and several nonanticoagulant properties such as antiproliferative, anti-inflammatory activity, and anticomplement effects. Although UFH has been widely replaced by LMWH, UFH is still the preferred anticoagulant of choice for patients undergoing cardiopulmonary bypass surgery, extracorporeal membrane oxygenation, and patients with high-risk mechanical cardiac valves requiring temporary bridging with a parenteral anticoagulant. UFH is a highly negatively charged molecule and binds many positively charged molecules, hence has unpredictable pharmacokinetics, and variable anticoagulant effect on an individual patient basis. Therefore, anticoagulant effects of UFH may not be proportional to the dose of UFH given to any individual patient. In this review, we discuss the anticoagulant and nonanticoagulant activities of UFH, differences between UFH and LMWH, when to use UFH, different methods of monitoring the anticoagulant effects of UFH (including activated partial thromboplastin time, heparin anti-Xa activity level, and activated clotting time), while discussing pros and cons related to each method and comparison of clinical outcomes in patients treated with UFH monitored with different methods based on available evidence.

Qualitative study of willingness and demand for participation in decision-making regarding anticoagulation therapy in patient undergoing heart valve replacement

BackgroundPromoting patient participation in decision-making aims to maintain the partnership between doctors and patients, reflect the patients’ goals, values, and preferences, and achieve patient-centered care. Realizing patient-centered care, shared collaboration between doctors and patients, and the decision-making process that considers the patients’ priorities and goals are the keys to high-quality health care. Therefore, it is indispensable to analyze the patients’ willingness to participate in the decision-making process and related participation needs regarding anticoagulation treatment for patients undergoing valve replacement.PurposeTo analyze the patients’ willingness to participate in the decision-making process and the participation needs of patients undergoing mechanical cardiac valve replacement in the process of anticoagulation therapy to provide a basis for promoting patients' participation in decision-making.MethodsUsing phenomenological research methods, data were collected through semistructured interviews. Patients were interviewed after mechanical valve replacement from June to August 2021 in a Grade A hospital in Nanjing. Data were analyzed according to the Colaizzi phenomenology method.ResultsThree major themes were identified from the data: strong willingness to participate but low actual participation, supportive needs, and family members’ participation.ConclusionsThis study guided interventions to encourage patients who underwent heart valve replacement to participate in the decision-making process. From the patient's perspective, obtaining support in the decision-making process and caregiver enthusiasm is important. This study prompted thoughts about the use of auxiliary tools and provided a reliable basis for constructing decision-making auxiliary programs to guide clinical practice.

The Efficacy and Safety of Thrombolytic Agents for Patients with Prosthetic Valve Thrombosis

Introduction: Prosthetic valve thrombosis (PVT) is a serious complication seen with mechanical prosthetic cardiac valves and is associated with high mortality. Emergency surgery (thrombectomy or valve replacement) had been the traditional treatment, but now with intravenous thrombolytic therapy as an alternative to emergency surgery in patients with PVT has shown excellent success rate and acceptable risk. This study is aimed to determine efficacy and safety of use of thrombolytic agents (tPA or STK) in patients with PVT. Materials and Methods: This was a retrospective, single-center study of patients with PVT admitted between 2004 and 2020 at a tertiary care center in North India. The diagnosis of PVT was based on a history of prosthetic heart valve replacement, clinical presentation, and by diagnostic methods. All patients received either tenecteplase or streptokinase given as a bolus dose of 2.5 lac units over ½ h, followed by 1 lac units/h for 24–48 h depending on clinical response and complication, whereas tenecteplase (1 mg/kg of body weight) was given as bolus. Results: Of 72 patients, 45 patients received t-PA as a thrombolytic drug. Complete success was obtained in 39 patients (86.66%), whereas partial success in 3 (17.77%) and failure in 3 (6.66%). Among the patients who received streptokinase (n = 27), complete success was found in 23 patients (85.19%), whereas partial success was seen in 3 (11.11%) and failure was seen in 1 patient (3.7%). Conclusion: Thrombolysis is a reasonable option in patients with PVT. Our study has reiterated that major factors for PVT are warfarin poor compliance and subtherapeutic international normalized ratio. Postclosure clinical follow-up along with patient education should be followed in patients with mechanical prosthetic valve.

Early Outcomes of Emergency Surgery for Left-Sided Mechanical Valve Thrombosis.

Valve thrombosis is a potentially lethal complication of mechanical cardiac valves. We examined the clinical characteristics as well as the early outcomes of patients undergoing emergency surgery for left-sided mechanical valve thrombosis. Between January 2012 and May 2020, 104 consecutive patients were offered an emergency redo surgery for acute mechanical valve thrombosis. Ninety-seven of these patients were included in the current study. The mean age was 34.2 ± 10.3 years. Most of the patients were females (61 patients), and 27 patients (27.8%) were pregnant. The mitral valve was the site of thrombosis in 81 patients. Inadequate anticoagulation was found in 60.8% of patients. The overall early mortality was 32.9% (32 patients) with an operative mortality of 25.7%. Outcomes in the pregnant subgroup tended to be worst with a maternal mortality in the range of 37%, and with fetal and neonatal survival as low as 33.3%. The overall mortality in cases of mechanical valve thrombosis warranting surgery remains high. Since inadequate anticoagulation seems to be one of the major precipitating factors, the current study highlights the need for improvements in anticoagulation practices. The use of tissue valves should also be contemplated more seriously in some younger patients, especially females expressing the desire for future pregnancies.

Incidence of maternal and fetal complications in pregnant with mechanical prosthetic cardiac valves: a cohort study

Abstract Background In developing countries, an unusually large number of women of childbearing age have mechanical valves because rheumatic fever and concomitant valvular heart disease are still common and most severely affect the young. Managing anticoagulation during pregnancy is challenging, and the rate of complications is relatively high. Purpose The aim of this study was to detect the incidence of maternal and fetal complications in pregnant women with prosthetic valve in a high-risk pregnancy unit in one of the developing countries. Methods This study included 106 pregnant women with prosthetic heart valves on oral anticoagulant therapy. Excluded from the study were patients with low ejection fraction (<50%), patients with other comorbidities that may affect the pregnancy outcomes and patients who were not willing to share their data. Patients were followed up since presentation to the high-risk pregnancy unit till delivery. At each visit, women were clinically assessed for the occurrence of complications (heart failure, infective endocarditis, prosthetic valve dysfunction, systemic emboli, new onset arrhythmia, antepartum hemorrhage, or death). Babies were evaluated by an Obstetrician for intrauterine growth retardation or fetal death, abortion, oligo or polyhydramnios, and congenital heart diseases. Results The mean age was 28.5±4.2 years, 58 patients (54.7%) had mitral valve prothesis, 34 (32.1%) had aortic valve prosthesis and 14 patients (13.2%) had double valve prothesis. Fifty-three patients (50%) received warfarin throughout pregnancy and the rest switched to heparin in the first trimester. Cerebrovascular stroke occurred in 4 patients (3.8%), all were on the 1st trimester and all were taking heparins. The mean gestational age at delivery was 36.2±4.8 weeks and the mean fetal birth weight was 2435±791.5 gm. Thirty-three abortions were reported and the mean gestational age for abortion was 13 weeks±6 days while the mean gestational age for intrauterine fetal death was 29±4 weeks, table. Two babies had congenital heart diseases (ventricular septal defect and patent ductus arteriosus) and in both, the mothers were taking warfarin >5 mg/day during the second and third trimesters. Conclusion In this tertiary care centre, the incidence of maternal complications was relatively small while the incidence of fetal complications was high, especially in mothers taking higher warfarin doses. Switching to heparin in the first trimester increased the risk of systemic embolization. Funding Acknowledgement Type of funding sources: None.

A clinical and in vitro assessment of outpatient parenteral benzylpenicillin and ceftriaxone combination therapy for enterococcal endovascular infections.

BackgroundAmoxicillin plus ceftriaxone combination therapy is now standard of care for enterococcal endocarditis. Due to amoxicillin instability in infusion devices, benzylpenicillin plus ceftriaxone may be substituted to facilitate outpatient parenteral antimicrobial therapy (OPAT) delivery, despite lack of guideline endorsement.ObjectivesTo assess the clinical efficacy of benzylpenicillin plus ceftriaxone for the management of enterococcal endovascular infections, in addition to assessing this combination’s in vitro synergy.Patients and methodsRetrospective cohort study assessing unplanned readmissions, relapses and mortality for 20 patients with endovascular Enterococcus faecalis infections treated with benzylpenicillin plus ceftriaxone delivered via OPAT. For a subset of isolates, synergism for both amoxicillin and benzylpenicillin in combination with ceftriaxone was calculated using a chequerboard method.ResultsPatients had endovascular infections of native cardiac valves (n = 11), mechanical or bioprosthetic cardiac valves (n = 7), pacemaker leads (n = 1) or left ventricular assistant devices (n = 1). The median duration of OPAT was 22 days, and the most frequent antimicrobial regimen was benzylpenicillin 14 g/day via continuous infusion and ceftriaxone 4 g once daily via short infusion. Rates of unplanned readmissions were high (30%), although rates of relapsed bacteraemia (5%) and 1 year mortality (15%) were comparable to the published literature. Benzylpenicillin less frequently displayed a synergistic interaction with ceftriaxone when compared with amoxicillin (3 versus 4 out of 6 isolates).ConclusionsLower rates of synergistic antimicrobial interaction and a significant proportion of unplanned readmissions suggest clinicians should exercise caution when treating enterococcal endovascular infection utilizing a combination of benzylpenicillin and ceftriaxone via OPAT.

6 months follow-up of patients using coagulation self testing by Coaguchek® INRange

CoaguChek® is a portable coagulometer that provides INR results in less than one minute from a single drop of blood taken from the tip of the finger. Its accuracy has been demonstrated but quality of life of self-testing adult patients has been poorly investigated. To evaluate change of self-confidence and quality of life of patients using self-testing INR. A follow-up questionnaire was sent (postmail or e-mail) to each patient 6 months after a collective educational session focused on anticoagulant treatment management and CoaguChek® training. Patients were asked to evaluate their quality of life since the beginning of coagulation self-testing (huge improvement, great improvement, moderate improvement, no improvement). A numeric analog scale (0–10) evaluated self-confidence and impact of the cardiac disease at the time of education and in the follow-up. 70 patients answered the questionnaire (76%). Huge or great improvement was frequent (31,4%; 52,9% respectively). Self-confidence improved (6,10; 7,23; P < 0,01) and impact of cardiac disease lowered (8,10; 7,55; P = 0,058) ( Fig. 1 ). Therapeutic education for patients with mechanical cardiac valve taking anticoagulation treatment combined with a training session to learn how to use the CoaguChek® is essential. Beyond safety goals, education, training and use of coagulation self-testing improves self-confidence of patients and lowers the impact of the cardiac disease.

Cholesterol crystal induced inflammation and mechanical cardiac valve injury: Implications for transcatheter aortic-valve replacement

The process of cardiac valve sclerosis and stenosis in non-rheumatic disease is related to inflammation via the innate immune system similar to atherosclerosis. Cardiac valve composition shares many features with arterial tissue. Cholesterol infiltration in the valve matrix results in cholesterol crystal formation and deposition that causes mechanical injury and triggers inflammation. Sclerotic human valve specimens as well as valves from atherosclerotic rabbit models reveal presence of cholesterol crystals and macrophage infiltration as seen in atherosclerosis. Lipid lowering by combination of simvastatin and ezetimibe demonstrates cholesterol reduction in valves only if used in a preventive manner. However, once the valve is infiltrated by cholesterol and crystals form in the tissue matrix, these become very difficult to extract and lipid lowering is no longer very effective. Furthermore, cholesterol crystals serve as a nidus for calcium phosphate deposition that distorts and stiffens the valve tissue leading to valve dysfunction. During Transcatheter Aortic Valve Replacement (TAVR) procedures, crystals can complicate the procedure by release of crystalline particles causing ischemic cerebral events and rupturing balloons.

Periprocedural and long-term safety and feasibility of direct oral anticoagulants in patients with biological valve undergoing radiofrequency catheter ablation for atrial fibrillation: a prospective multicenter study.

Direct oral anticoagulants (DOACs) are contraindicated in patients with atrial fibrillation (AF) and mechanical cardiac valves. However, safety and efficacy are controversial in patients with biological cardiac valves. We report the safety and feasibility of periprocedural and long-term treatment with DOACs in patients with biological valves undergoing ablation for AF. A total of 127 patients with AF and biological cardiac valve undergoing CA on uninterrupted DOAC were matched by gender and age with 127 patients with AF and biological cardiac valves undergoing CA on uninterrupted warfarin. All patients were anticoagulated for at least 3-4weeks prior to ablation with either rivaroxaban (70%) or apixaban (30%), which were continued for at least 3months and subsequently based on CHA2DS2-VASc score. Mean age of the study population was 63.0 ± 10.9 with 66% being male. The majority of patients on NOACs had aortic valve replacement (59%), while mitral valve was replaced in 41% of patients, which did not differ from the matched cohort on coumadin (aortic valve 57% and mitral valve 43%, (p = 0.8) (p = 0.8), respectively). The CHADS2 score was ≥ 2 in 90 patients (71.0%) on DOAC and 86 patients in (68%) the control (p = 0.6) group. Patients underwent ablation predominantly with uninterrupted rivaroxaban [89 (70%)], while the remaining 38 patients (30%) underwent ablation while on apixaban. Two groin hematomas were observed periprocedurally in both groups. No stroke/transient ischemic attack (TIA) was observed both periprocedurally and at long-term follow-up in either group. Periprocedural and long-term administration of DOACs in patients with biological cardiac valves undergoing AF ablation appears as safe as warfarin therapy.

Genotype-guided warfarin dosing may benefit patients with mechanical aortic valve replacements: randomized controlled study

This prospective, single-blind, randomized study was designed to evaluate the effect of genotype-based warfarin dosing compared with standard warfarin dosing in Korean patients with mechanical cardiac valves. Patients were assigned to either the genotype-based dosing group or the standard dosing group using stratified block randomization. The genotype-based dosing equation was adopted from a previous study which included VKORC1 rs9934438, CYP2C9 rs1057910, CYP4F2 rs2108622, and age. Primary outcomes included the percentage of time in the therapeutic range (pTTR): (i) during the first week following initiation of warfarin therapy, (ii) during hospitalization and (iii) until the first outpatient visit. A total of 91 patients were included in the analysis, 42 treated with genotype-based warfarin dosing and 49 treated with standard warfarin dosing. The genotype frequency differences of the three SNPs included in this study (ie, VKORC1, CYP2C9, CYP4F2), between the genotype-based dosing and standard dosing groups were not different. The genotype-based dosing group trended toward higher pTTR when compared with the standard dosing group, although this difference was not statistically significant. In patients with aortic valve replacement, TTRTraditional and TTRRosendaal were significantly higher in the genotype-based dosing group when compared with the standard dosing group during the first week following treatment initiation [ie, 58.5% vs. 38.1% (p = 0.009) and 64.0% vs. 44.6% (p = 0.012), respectively]. Based on the results, the genotype-guided dosing did not offer a significant clinical advantage, but a possible benefit in patients with aortic valve replacement has been suggested.

APOB gene polymorphisms may affect the risk of minor or minimal bleeding complications in patients on warfarin maintaining therapeutic INR.

The purpose of this study was to investigate influence of gene polymorphisms of APOB and APOE on risk of bleeding complications at therapeutic INR, during warfarin treatment in Korean patients with mechanical cardiac valves. The study included 142 patients from the EwhA-Severance Treatment Group (EAST) of Warfarin. A total of 12 SNPs was investigated. Five SNPs of APOB (c.13013G>A, c.1853C>T, c.1594C>T, c.293C>T, and c.7545C>T) and five SNPs of APOE (g.4798T>G, g.6406G>A, g.10413T>C, c.388T>C, and c.526C>T) were selected. In addition to selected SNPs, VKORC1 g.6399C>T, and CYP2C9 c.1075A>C, which were known to have significant effects on warfarin stable doses, were also included in the study. Two SNPs of APOB (c.293C>T and c.1853C>T) were associated with bleeding complications. T allele carriers of c.293C>T had 8.6 times (95% CI 2.9-25.5, p < 0.001) increased risk of bleeding, and attributable risk was 88.3%. C allele carriers of c.1853C>T had 6.4 times (95% CI 2.3-17.9, p < 0.001) increased risk of bleeding after adjusting for covariates (attributable risk of 84.3%). AUROC values of models that included c.1853C>T and c.293C>T were 0.771 and 0.802, respectively. Among demographic characteristics, age was the only significant factor. This study revealed that APOB was associated with bleeding complications in patients with warfarin treatment after mechanical cardiac valves.

Significance of CYP4F2 polymorphism on oral anticoagulation therapy with acenocoumarol in South Indian patients with mechanical heart valves

BackgroundThe coumarin group of oral anticoagulants has a narrow therapeutic range and wide inter-individual variability. Polymorphism of VKORC1 and CYP2C9 genes are the major genetic determinants of the drug-dose response. Our study aimed to investigate the role of CYP4F2 (1347 G > A) polymorphism on the acenocoumarol daily dose requirement, and its interaction with VKORC1 and CYP2C9 polymorphism. Methods301 Rheumatic Heart Disease (RHD) patients with mechanical cardiac valves were recruited. Genotyping for CYP4F2, VKORC1 and CYP2C9 was done by PCR-RFLP. CYP4F2 genotype distribution GG, GA and AA was 23.5%, 51.5% and 25% respectively. The mean daily dose requirement for variant homozygous patients (AA) was 0.46 folds more when compared to wild type (GG) (Adjusted OR 0.46; 0.21–0.99, p = .048). However, on combined genotype analysis of CYP4F2, VKORC1 and CYP2C9 there was no significant difference in mean dose requirement. ConclusionThe homozygous genotype (AA) of CYP4F2 gene was more prevalent in our study cohort. No significant association was found between CYP4F2 gene polymorphism and acenocoumarol mean dose requirement, both when analyzed individually and in combination with VKORC1 and CYP2C9 polymorphisms.

Prosthetic valve thrombosis - association of genetic polymorphisms of VKORC1, CYP2C9 and CYP4F2 genes.

Prosthetic Valve Thrombosis (PVT), in spite of the advances in the valve design and the material used, remains a serious complication of mechanical cardiac valve replacement. The factors influencing the development of PVT are: thrombogenicity of the valve, hemodynamics of the transprosthetic blood flow and ineffective anticoagulation. Genetic polymorphism of the genes VKORC1 (-1639 G > A and 1173 C > T), CYP2C9 (∗2 & ∗3 alleles) and CYP4F2 (1347 G > A) are known to influence the anticoagulant dose-effect response. Since there has not been any earlier study on the direct influence of gene polymorphism on the development of PVT, we investigated into this association.Genotyping for the genes VKORC1, CYP2C9 and CYP4F2 was carried out by conventional PCR-RFLP method for 91 consecutive PVT patients. Subjects of our earlier study served as controls (n = 136).Female patients and patients with smaller prosthetic valve size were more prone to developing PVT (68%, n = 62). Patients bearing A allele of CYP4F2 1347 G > A polymorphism exhibited a fivefold increased risk of PVT (OR = 5.022 (1.39–18.04), P = .013). G allele of VKORC1 when analyzed in combination of genotypes showed a fourteen fold increased risk for developing PVT (OR = 14.25 (5.52–36.77), P = 0.001). CYP2C9 (∗2&∗3) gene polymorphism did not show any significant association with PVT (OR = 1.54 (0.128 – 18.82), P = .731).Patients bearing A allele of CYP4F2 showed an increased risk of developing PVT in our case – control study.

A novel survey examining the level of knowledge about anticoagulant and anti-infectious prophylaxis in patients after mechanical cardiac valve implantation.

A novel survey examining the level of knowledge about anticoagulant and anti-infectious prophylaxis in patients after mechanical cardiac valve implantation.

Combining oral anticoagulation and antiplatelet therapies: appropriate patient selection.

Anticoagulant therapy and antiplatelet therapy are used regularly for prevention of arterial and venous thrombosis, and combinations of the two drug classes are seen with relative frequency in clinical practice. While co-prescribing is as high as 39-55% in some real-world cohort studies, the number of patients that meet criteria for combination therapy based on the overall body of evidence is likely much lower. This may not always be realized by prescribers, and many patients may be continued on long term combination therapies that provide little additional benefit, and carry significant risk for harm. Given the heightened bleeding risk with combination therapies, prescribers should readily reassess the risk: benefit ratio in all patients on combination therapies. Combined antiplatelet and anticoagulant therapy should be used only in those with a low risk of bleeding who have a higher risk of thromboembolic disease events. Most patients with coronary artery disease, atrial fibrillation, peripheral arterial disease, or bioprosthetic cardiac valves will not benefit from combining antiplatelet and anticoagulant therapies. Conversely, patient populations more likely to derive benefit from antiplatelet-anticoagulant combinations include those with mechanical cardiac valves, patients undergoing percutaneous cardiac intervention who have another indication for anticoagulant therapy, and patients with recurrent thrombotic events while being treated with a single agent. This article will attempt to provide readers with a framework to assess which patient populations are likely to derive the greatest benefit with combination anticoagulant-antiplatelet therapies relative to the weighted risk for bleeding.

Adjustments to warfarin dosing after gastric bypass and sleeve gastrectomy

BackgroundWarfarin dosing after bariatric surgery may be influenced by alterations in gastrointestinal pH, transit time, absorptive surface area, gut microbiota, food intake, and adipose tissue. ObjectivesThe aim of this study was to describe trends in warfarin dosing after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). SettingSingle academic center. MethodsAll patients chronically on warfarin anticoagulation before RYGB or SG were retrospectively identified. Indications for anticoagulation, history of bleeding or thrombotic events, perioperative complications, and warfarin dosing were collected. ResultsFifty-three patients (RYGB n = 31, SG n = 22) on chronic warfarin therapy were identified (56.6% female, mean 54.4 ± 11.7 yr of age). Of this cohort, 34.0% had prior venous thromboembolic events, 43.4% had atrial fibrillation, and 5.7% had mechanical cardiac valves. Preoperatively, the average daily dose of warfarin was similar in the RYGB group (8.3 ± 4.1 mg) and SG group (6.9 ± 2.8 mg). One month after surgery, mean daily dose of warfarin was reduced 24.1% in the RYGB group (P<.001) and 23.2% in the SG group (P = .002). At 12 months postoperatively, the required daily warfarin dose compared with baseline remained statistically different (RYGB: 6.8 ± 3.8 mg; SG: 6.1 ± 2.0 mg). ConclusionsThe warfarin dose is expected to be decreased by approximately 25% from preoperative levels after both RYGB and SG. Lower dose requirement within the first month after bariatric surgery is followed by a trend toward increased warfarin dose requirements, but remain less than baseline. Because dose requirements change constantly over time, frequent postoperative monitoring of the international normalized ratio is recommended.

Evaluation of bleeding risk in patients on anticoagulation for mechanical cardiac valve operated for benign prostatic obstruction

To evaluate bleeding risk in patients on anticoagulation for mechanical cardiac valve operated for benign prostatic obstruction (BPO). Fifty-eight patients operated between 1998 and 2014, in seven French departments of Urology were included. Forty-five patients were operated by conventional surgery (transurethral resection of the prostate 38, open simple prostatectomies 7), and 13 patients were operated by Greenlight™ photovaporization of the prostate (PVP). In order to assess bleeding risk, blood transfusion was considered as the primary outcome. Fifteen (26%) patients received blood transfusion in the postoperative period. Mean duration of hospitalization was 8.5days. Secondary surgery was required in 12cases (21%), including endoscopic clot removal under general anaesthesia in 10 patients, and suprapubic haemostasis in 3 patients. One patient died 72hours after transurethral resection of the prostate because of a massive pulmonary embolism. Two independent predictors of blood transfusion were identified: conventional surgery use versus PVP, and high preoperative PSA. Blood transfusion rate was significantly lower in the group of patients operated by PVP compared to conventional surgery (0% versus 33%, P=0.010). In addition, the laser surgery was associated with shorter duration of hospitalization (3.4days versus 9.9days, P=0.014). However, it was not found any significant difference between patients operated by PVP compared to conventional surgery in terms of secondary bleeding (3/13 vs 8/45, P=0.7), or second surgery (2/13 vs 10/45, P=0.5). Bleeding risk of BPO surgery in patients with mechanical cardiac valve is high. The PVP seems to decrease significantly the early haemorrhagic risk compared to classic surgical procedures for patients with mechanical cardiac valve. 4.

PP-102 [AJC » Diagnosis and Treatment of Valvular Heart Disease] Is Fasting For Ramadan Safe For Patients Who Have Mechanical Cardiac Valves?

PP-102 [AJC » Diagnosis and Treatment of Valvular Heart Disease] Is Fasting For Ramadan Safe For Patients Who Have Mechanical Cardiac Valves?

Influence of NR3C1 and VDR polymorphisms on stable warfarin dose in patients with mechanical cardiac valves

ObjectivesThe aim of this study was to evaluate the associations between polymorphisms of VKORC1, CYP2C9, CYP4F2, NR3C1 and VDR genes and stable warfarin doses in Korean patients with mechanical heart valves. MethodsSeventeen single-nucleotide polymorphisms (SNPs) in 204 patients with stable warfarin dose were analyzed: VKORC1 (rs9934438), CYP2C9 (rs1057910), CYP4F2 (rs2108622), NR3C1 (rs41423247, rs1800445, rs56149945, rs10052957, rs6198, rs33388, rs6196, and rs244465), and VDR (rs1544410, rs11568820, rs731236, rs757343, rs7975232, and rs2228570). Statistical analyses were conducted to evaluate the associations of gene variations with stable warfarin dose. Number needed to genotype was obtained by calculating the percentage of patients whose predicted dose was at least 20% higher or lower than the actual stable dose. ResultsThe combined genotypes of rs7975232 and rs2228570 of the VDR gene revealed a significant association with stable warfarin dose, along with VKORC1, CYP2C9, and CYP4F2 polymorphisms. Patients with the genotype combination GT,TT/CT,CC of VDR rs7975232/rs2228570 required significantly higher stable warfarin dose (5.79±2.02mg) than those with the other genotypic combinations (5.19±1.78mg, p=0.034). Multivariate analysis showed that VDR rs7975232/rs2228570 explained 2.0% of the 47.5% variability in overall warfarin dose. Adding VDR SNP combinations to the base model including non-genetic variables (age, sex, and body weight) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 41. ConclusionsThis study showed that stable warfarin dose is associated with VDR SNPs along with VKORC1, CYP2C9, and CYP4F2 SNPs.

Time to achieving therapeutic international normalized ratio increases hospital length of stay after heart valve replacement surgery

Achieving a therapeutic international normalized ratio (INR) before hospital discharge is an important inpatient goal for patients undergoing mechanical cardiac valve replacement (MCVR). The use of clinical algorithms has reduced the time to achieve therapeutic INR (TTI) with warfarin therapy. Whether TTI prolongs length of stay (LOS) is unknown. Patients who underwent MCVR over a consecutive 42-month period were included. Clinical data were obtained from the Society of Thoracic Surgeons Adult Cardiac Surgery database and electronic medical records. Therapeutic INR was defined as per standard guidelines. Warfarin dose was prescribed using an inpatient pharmacy-managed algorithm and computer-based dosing tool. International normalized ratio trajectory, procedural needs, and drug interactions were included in warfarin dose determination. There were 708 patients who underwent MCVR, of which 159 were excluded for reasons that would preclude or interrupt warfarin use. Among the remainder of 549 patients, the average LOS was 6.4days and mean TTI was 3.5days. Landmark analysis showed that subjects in hospital on day 4 (n=542) who achieved therapeutic INR were more likely to be discharged by day 6 compared with those who did not achieve therapeutic INR (75% vs 59%, P<.001). Multivariable proportional hazards regression with TTI as a time-dependent effect showed a strong association with discharge (P=.0096, hazard ratio1.3) after adjustment for other significant clinical covariates. Time to achieve therapeutic INR is an independent predictor of LOS in patients requiring anticoagulation with warfarin after MCVR surgery. Alternative dosing and anticoagulation strategies will need to be adopted to reduce LOS in these patients.