Novel Gene Polymorphisms for Stable Warfarin Dose in a Korean Population: Genome-Wide Association Study.

Warfarin has a narrow therapeutic window and high intra- and inter-individual variability. Considering that many published papers on genotype-guided dosing are derived from European populations, the aim of this study was to investigate novel genetic variants associated with the variability of stable warfarin dose in the Korean population with cardiac valve replacement, using the GWAS approach. This retrospective cohort study was performed from January 1982 to December 2020 at the Severance Cardiovascular Hospital of Yonsei University College of Medicine. GWAS was performed to identify associations between genotypes and the warfarin maintenance dose, by comparing the allele frequency of genetic variants between individuals. Then, the extent of genetic and non-genetic factors on the dose variability was determined by multivariable regression analysis. The study enrolled 214 participants, and the most robust signal cluster was detected on chromosome 16 around VKORC1. Followed by VKORC1, three novel variants (NKX2-6 rs310279, FRAS1 rs4386623, and FAM201A rs1890109) showed an association with stable warfarin dose requirement in univariate analysis. The algorithm was constructed by using multivariable analysis that includes genetic and non-genetic factors, and it could explain 58.5% of the variations in stable warfarin doses. In this variability, VKORC1 rs9934438 and FRAS1 rs4386623 accounted for 33.0% and 9.9%, respectively. This GWAS analysis identified the fact that three novel variants (NKX2-6 rs310279, FRAS1 rs4386623, and FAM201A rs1890109) were associated with stable warfarin doses. Additional research is necessary to validate the results and establish personalized treatment strategies for the Korean population.

Trends in Heart Valve Surgery in Korea: A Report from the Heart Valve Surgery Registry Database.

Background: In this study, we present recent trends in heart valve surgery in Korea through analyses of data from the Korea Heart Valve Surgery Registry (KHVSR). Methods: We enrolled 8,981 patients who were registered in the KHVSR from 2017 to 2020. Yearly trends in patients' baseline characteristics, surgical profiles, and early mortality rates were explored. The observed/expected mortality ratio (O/E ratio), calculated from the actual mortality in the KHVSR and the predicted mortality estimated using the EuroSCORE II, was also analyzed. Results: The proportion of aortic valve surgery significantly increased from 56.8% in 2017 to 60.3% in 2020. The proportion of all combined procedures and minimally invasive surgery significantly increased over the 4-year study period. The operative mortality rate was 2.9% in the entire cohort, while mitral valve repair showed the lowest mortality risk (0.9%). The mortality rates of isolated aortic valve replacement (AVR) significantly decreased from 2.1% in 2017 to 0.8% in 2020 (p=0.016). Overall, the O/E ratio was 0.784 (95% confidence interval [CI], 0.677-0.902) demonstrating significantly lower actual mortality risks than expected based on the EuroSCORE II. In particular, the O/E ratios were as low as 0.364 (95% CI, 0.208-0.591) for isolated AVR. Conclusion: The recent data from the KHVSR showed increasing trends for complex procedures and minimally invasive surgery in heart valve surgery in Korea, and demonstrated remarkably low risks of operative mortality.

Gene Polymorphisms of the Renin-Angiotensin System and Bleeding Complications of Warfarin: Genetic-Based Machine Learning Models.

BACKGROUND: This study aimed to investigate the effects of genetic variants and haplotypes in the renin-angiotensin system (RAS) on the risk of warfarin-induced bleeding complications at therapeutic international normalized ratios (INRs). METHODS: Four single nucleotide polymorphisms (SNPs) of AGT, two SNPs of REN, three SNPs of ACE, four SNPs of AGTR1, and one SNP of AGTR2, in addition to VKORC1 and CYP2C9 variants, were investigated. We utilized logistic regression and several machine learning methods for bleeding prediction. RESULTS: The study included 142 patients, among whom 21 experienced bleeding complications. We identified a haplotype, H2 (TCG), carrying three SNPs of ACE (rs1800764, rs4341, and rs4353), which showed a significant relation with bleeding complications. After adjusting covariates, patients with H2/H2 experienced a 0.12-fold (95% CI 0.02-0.99) higher risk of bleeding complications than the others. In addition, G allele carriers of AGT rs5050 and A allele carriers of AGTR1 rs2640543 had 5.0- (95% CI 1.8-14.1) and 3.2-fold (95% CI 1.1-8.9) increased risk of bleeding complications compared with the TT genotype and GG genotype carriers, respectively. The AUROC values (mean, 95% CI) across 10 random iterations using five-fold cross-validated multivariate logistic regression, elastic net, random forest, support vector machine (SVM)-linear kernel, and SVM-radial kernel models were 0.732 (0.694-0.771), 0.741 (0.612-0.870), 0.723 (0.589-0.857), 0.673 (0.517-0.828), and 0.680 (0.528-0.832), respectively. The highest quartile group (≥75th percentile) of weighted risk score had approximately 12.0 times (95% CI 3.1-46.7) increased risk of bleeding, compared to the 25-75th percentile group, respectively. CONCLUSION: This study demonstrated that RAS-related polymorphisms, including the H2 haplotype of the ACE gene, could affect bleeding complications during warfarin treatment for patients with mechanical heart valves. Our results could be used to develop individually tailored intervention strategies to prevent warfarin-induced bleeding.

TGF-ß1 polymorphism increases the risk of bleeding complications in patients on oral anticoagulant after cardiac valve replacement.

Although an elevated INR is highly associated with an increased risk of warfarin-associated bleeding, it has been reported that some patients also experience bleeding complications at therapeutic INRs. TGF-ß1 polymorphisms has been reported to cause vascular malformations, resulting in bleeding complications, but there are few published genetic studies regarding bleeding complications in patients on warfarin therapy. This study aimed to determine if there is an association between transforming growth factor beta-1 (TGF-ß1) polymorphisms and bleeding complications in patients who maintain international normalized ratios (INRs) of 2.0-3.0 with warfarin therapy after cardiac valve replacement. Eleven single nucleotide polymorphis (SNPs) of TGF-ß1 (rs1800469, rs2241718, rs4803455, rs2241717, rs2241716, rs2241715, rs2241714, rs11083616, rs2317130, rs747857, and rs1982073) were analyzed. Univariate and multivariable analyses were conducted to evaluate the associations between genetic polymorphisms and bleeding risk. Attributable risk and the number needed to genotype (NNG) were calculated to identify the potential clinical value of genotyping. A discrimination of model was assessed via an analysis of the area under the receiver operating curve (AUROC). To test the model's goodness of fit, a Hosmer-Lemeshow test was performed. Of 142 patients, 21 experienced bleeding complications. Among analyzed single nucleotide polymorphis (SNPs) of TGF-ß1 (rs1800469, rs2241718, rs4803455, rs2241717, rs2241716, rs2241715, rs2241714, rs11083616, rs2317130, rs747857, and rs1982073), AA genotype carriers in rs2241718 had about 5.5 times more bleeding complications than those with the G allele after adjusting for other confounders. The attributable risk and NNG for rs2241718 were 81.9% and 57.8, respectively. The presence of atrial fibrillation and myocardial infarction increased bleeding complications 3.9- and 9.8-fold, compared with those without atrial fibrillation and myocardial infarction, respectively. Bleeding complications during warfarin therapy in patients with mechanical heart valves were associated with TGF-ß1 polymorphisms as well as atrial fibrillation and myocardial infarction.

A Risk Prediction Model for Operative Mortality after Heart Valve Surgery in a Korean Cohort.

BACKGROUND: This study aimed to develop a new risk prediction model for operative mortality in a Korean cohort undergoing heart valve surgery using the Korea Heart Valve Surgery Registry (KHVSR) database. METHODS: We analyzed data from 4,742 patients registered in the KHVSR who underwent heart valve surgery at 9 institutions between 2017 and 2018. A risk prediction model was developed for operative mortality, defined as death within 30 days after surgery or during the same hospitalization. A statistical model was generated with a scoring system by multiple logistic regression analyses. The performance of the model was evaluated by its discrimination and calibration abilities. RESULTS: Operative mortality occurred in 142 patients. The final regression models identified 13 risk variables. The risk prediction model showed good discrimination, with a c-statistic of 0.805 and calibration with Hosmer-Lemeshow goodness-of-fit p-value of 0.630. The risk scores ranged from -1 to 15, and were associated with an increase in predicted mortality. The predicted mortality across the risk scores ranged from 0.3% to 80.6%. CONCLUSION: This risk prediction model using a scoring system specific to heart valve surgery was developed from the KHVSR database. The risk prediction model showed that operative mortality could be predicted well in a Korean cohort.

Early and Two-year Outcomes after Sutureless and Conventional Aortic Valve Replacement: a Nationwide Population-based Study.

BACKGROUND: We compared early and 2-year clinical outcomes of sutureless aortic valve replacement (SAVR) with conventional aortic valve replacement (CAVR) in a nationwide study based on claims data. METHODS: From December 2016 to November 2018, 3,173 patients underwent bioprosthetic aortic valve replacements. SAVR and CAVR were performed in 641 and 2,532 patients, respectively. Propensity score-matched analysis was performed in 640 patient pairs. RESULTS: Operative mortality rate was 2.8% without significant differences between the SAVR (3.4%) and CAVR (2.3%) groups (P = 0.324). There were no significant differences in postoperative morbidities between the groups except for permanent pacemaker (PPM) implantation. PPM implantation rate was significantly higher in the SAVR (3.8%) than in the CAVR group (0.9%) (P < 0.001). One- and two-year overall survival was 89.1% and 87.5%, respectively, without significant differences between the groups (SAVR group vs. CAVR grouP = 89.9% and 90.5% vs. 87.2% and 88.7%, respectively; P = 0.475). There were no significant differences in the cumulative incidence of cardiac death, stroke, aortic valve reoperation and infective endocarditis between the groups. Cumulative PPM implantation incidence at 6 months in the CAVR was 1.1%, and no patient required PPM implantation after 6 months. In the SAVR, the cumulative PPM implantation incidence at 0.5, one, and two years was 3.9%, 5.0% and 5.6%, respectively. The cumulative PPM implantation rate was higher in the SAVR group than in the CAVR group (P < 0.001). CONCLUSION: Early and 2-year clinical outcomes between SAVR and CAVR were not different except for a high rate of permanent pacemaker implantation in the SAVR group.

Long-term Clinical Impacts of Functional Mitral Stenosis After Mitral Valve Repair.

BACKGROUND: The relationship between functional mitral stenosis (MS) after mitral valve (MV) repair and long-term clinical outcomes is not fully understood. Therefore, we reviewed an institutional series to identify the determinants of functional MS and its effect on long-term clinical outcomes after MV repair for degenerative mitral regurgitation. METHODS: Between January 1990 and December 2015, 792 patients who underwent MV repair for degenerative mitral regurgitation were retrospectively enrolled and divided into 2 groups: functional MS (n = 192) (≥5 mm Hg mean diastolic pressure gradient across the MV) and nonfunctional MS (n = 600) (<5 mm Hg mean diastolic pressure gradient). Mean follow-up was 11.6 ± 5.8 years. RESULTS: After propensity-score matching, patients' characteristics were comparable between groups (n = 192/group). At 20 years, the functional MS group had significantly lower rates of freedom from new-onset atrial fibrillation (73.0% ± 5.6% versus 93.2% ± 2.3%; P = .003), overall survival (72.1% ± 4.6% versus 85.6% ± 4.3%; P = .010), and freedom from MV reoperation (82.8% ± 4.1% versus 92.5% ± 4.2%; P = .019) than the nonfunctional group. The functional MS group also had a significantly greater postoperative left atrial volume index and tricuspid regurgitation grade. A small left ventricular end-diastolic dimension (hazard ratio = 0.975; 95% confidence interval, 0.955-0.996; P = .022) and annuloplasty ring (hazard ratio = 0.757; 95% confidence interval, 0.685-0.837; P < .001) were independent risk factors for functional MS. CONCLUSIONS: A small left ventricle and annuloplasty ring increased the risk for functional MS after MV repair and was associated with progressive left atrial enlargement and tricuspid regurgitation exacerbation. As a result, functional MS increased the risk for new-onset atrial fibrillation, MV reoperation, and decreased long-term survival.

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.

The fate of residual aortic regurgitation after ascending aorta replacement in type A aortic dissection.

OBJECTIVE: This study aimed to evaluate the changes in postoperative aortic regurgitation (AR) and determine the predictors of significant AR and root reoperation after ascending aortic replacement (AAR) in patients with acute type A aortic dissection. METHODS: From January 1995 to December 2017, 271 consecutive patients underwent valve/root-preserving AAR (n = 225) and root replacement (n = 46). AR grade trend over time was analyzed by the ordinal mixed-effects model. Significant AR was defined as AR grade ≥3+ during the follow-up period. Predischarge and follow-up echocardiograms were obtained in 95.6% and 88.8% of enrolled patients, respectively. RESULTS: At predischarge, postoperative ≥2+ AR was present in 20 (9.3%) and 1 (2.3%) patients in the AAR and root replacement groups, respectively. With increasing time after surgery, the grade of AR increased. At 10 years, 4.6% of patients had developed 3+ or 4+ AR. Considering death as the competing risk, the 10-year cumulative incidence of significant AR was significantly higher in the AAR than in the root replacement group (12.3% vs 2.2%; P = .047). The risk of root reoperation at 10 years was not different between the groups (P = .118). On Cox analysis, preoperative ≥3+ AR (P = .002), postoperative ≥2+ AR (P = .040), and false to true lumen ratio (P = .005) were associated predictors of significant AR. CONCLUSIONS: Although valve/root-preserving AAR demonstrated reasonable long-term outcomes when compared with root replacement, preoperative ≥3+ AR, postoperative ≥2+ AR, and high false to true lumen ratio significantly increased the risk of significant AR. Therefore, careful echocardiographic surveillance may be warranted in patients with postoperative ≥2+ AR and small true lumen.

Concomitant Wrapping of a Moderately Dilated Ascending Aorta during Aortic Valve Replacement: Postoperative Remodeling of a Distinctive Aorta.

PURPOSE: The long-term outcomes of aortic wrapping in patients with ascending aortic aneurysms, which are rare, but can be fatal, remain poorly understood. This retrospective study analyzed the outcomes of aortic diameter, including aortic root, ascending aorta, and proximal arch diameters, after aortic wrapping during aortic valve replacement surgery. MATERIALS AND METHODS: Ninety-six patients with ascending aortic dilation of 40-55 mm who underwent aortic wrapping during aortic valve replacement were selected for this study. Aortic diameter was measured at three levels perioperatively and at follow-up (median time of 9.1±4.2 years). A linear mixed-effects model was used to analyze aortic diameter expansion. RESULTS: Freedom from adverse aortic events (aortic dissection or rupture, reoperation, or sudden death) at 10 years was 97.9%. No significant dilation at the level of the sinuses of Valsalva (0.069 mm/year, p=0.524) or ascending aorta (0.152 mm/year, p=0.124) was observed. Significant dilation occurred at the proximal aortic arch (0.343 mm/year, p=0.006). Subgroup analysis with a multivariable linear mixed model identified initial ascending aortic diameter to be a significant predictor of proximal arch dilation (p=0.032). Receiver operating characteristic curve analysis revealed that the cut-off for the prediction of proximal arch redilation was an initial mid-ascending aortic diameter of 47.0 mm (area under the curve 0.747, 90% confidence interval 0.613-0.881, p=0.023). CONCLUSION: Aortic wrapping could be considered as a safe and long-term therapeutic option. Redilation of the proximal arch should be carefully observed during long-term follow-up.

Effects of Polymorphisms in Myc-Related Genes on Bleeding Complications in Patients with Stable Warfarin Responses.

OBJECTIVES: This study aimed to identify the possible effects of Myc and 8q24 polymorphisms on bleeding complications in patients who maintained international normalized ratio (INR) of 2.0-3.0 with warfarin therapy after cardiac valve replacement. METHODS: Twenty-five single nucleotide polymorphisms were analyzed, including VKORC1, CYP2C9, Myc, and 8q24. Univariate and multivariate analyses were conducted to evaluate the associations between genetic polymorphisms and bleeding complications. Attributable risk and the number needed to genotype (NNG) were also calculated to evaluate the potential clinical value of genotyping. RESULTS: We included 142 patients, among whom 21 experienced bleeding complications. Multivariate models showed that patients carrying the CC genotype of rs6983561 and the A allele of rs13281615 at 8q24 had 27.6- and 10.0-fold higher bleeding complications, compared with patients with the A allele and the GG genotype, respectively. For rs6983561, the attributable risk and NNG were 96.4% and 36.8, respectively, whereas, for rs13281615, the attributable risk and NNG were 90.0% and 8.3, respectively. Atrial fibrillation was associated with a 5.5-fold increased risk of bleeding complications. The AUROC value was 0.761 (95% CI 0.659-0.863, p<0.001), and the Hosmer-Lemeshow test showed that the fitness of the multivariate analysis model was satisfactory (χ 2=0.846; 3 degrees of freedom; p=0.838). CONCLUSIONS: Bleeding complications during warfarin therapy were associated with 8q24 polymorphisms and atrial fibrillation in patients with mechanical heart valves.

Association between HNF4A mutations and bleeding complications in patients with stable international normalized ratio.

OBJECTIVES: This study aimed to determine the association between hepatocyte nuclear factor 4 alpha (HNF4A) polymorphisms and bleeding complications in patients on warfarin with international normalized ratios between 2.0 and 3.0 after cardiac valve replacement. METHODS: Nineteen single nucleotide polymorphisms of HNF4A in addition to VKORC1 rs9934438 and CYP2C9 rs1057910 were analyzed. Univariate and multivariate analyses were conducted to evaluate associations between genetic polymorphisms and bleeding risk. Attributable risk and number needed to genotype (NNG) were calculated to assess clinical value of genotyping. RESULTS: Of 142 patients, 21 experienced bleeding complications. Multivariate logistic regression analysis was conducted using factors with P <0.1 in univariate analysis. Multivariate analysis showed that patients with the CC genotype of rs6130615 had an 8.4-fold increased risk of bleeding, compared with patients with the T allele. Attributable risk and NNG were 88.1% and 32.2, respectively. Patients with the TT genotype of rs3212191 had a 3.8-fold increased risk of bleeding, compared with C allele carriers, while patients with variant-type homozygotes for rs1884613 showed an 8.7-fold higher bleeding complication than C allele carriers. The attributable risk/NNG of rs3212191 and rs1884613 were 73.4%/17.6 and 88.5%/22.8, respectively. Among comorbidities, atrial fibrillation was the only significant risk factor for bleeding complications. CONCLUSION: Bleeding complications during warfarin therapy in patients with mechanical heart valves were associated with HNF4A polymorphisms and atrial fibrillation.

Historical Perspectives of Korean Society for Thoracic and Cardiovascular Surgery: Inauguration and Activities of the Historical Records Preservation Committee.

The Korean Society for Thoracic and Cardiovascular Surgery (KTCVS) was founded in 1968 and celebrated the 50th anniversary of its founding in 2018. The launch of the KTCVS may seem somewhat recent, given that the American Association for Thoracic Surgery was founded in 1917. However, considering the circumstances of the Korean medical community after the Japanese occupation (1910-1945), World War II (1940-1945), and the Korean War (1950-1953), this apparent delay is understandable. Even before the foundation of the KTCVS, the early pioneers of thoracic and cardiovascular surgery promptly adopted medical technologies from more advanced countries such as the United States, and contributed significantly to both cardiac and thoracic surgery despite difficult circumstances. In 2012, before the 50th anniversary of the founding of the KTCVS, members shared the opinion that objective records of the activities of the early pioneers should be identified and preserved, and reacted positively towards the necessity for historians who would preserve such records. With this background, the Historical Records Preservation Committee of the KTCVS (hereinafter, referred to as 'the Committee') was launched. The Committee published a white paper on the history of thoracic and cardiovascular surgery in 2015 and held an exhibition of the achievements of the pioneers at the 50th anniversary of the founding of the KTCVS. The Committee also published a book entitled "The history of Korean thoracic surgery with photographs: celebrating the 50th anniversary of the society." The Committee will keep making efforts to find and preserve materials related to activities during the early development of thoracic and cardiovascular surgery in Korea.

Genetic variations in the transcription factors GATA4 and GATA6 and bleeding complications in patients receiving warfarin therapy.

Purpose: GATA4 and GATA6 are known to have potential roles in vascular regulation by affecting vascular smooth muscle cell differentiation and atrial natriuretic peptide levels. The aim of this retrospective study was to investigate the associations between GATA4 and GATA6 polymorphisms and bleeding complication risk at a therapeutic international normalized ratio (INR) in patients with mechanical heart valves. Patients and methods: Study patients were included from the Ewha-Severance Treatment (EAST) Group of Warfarin. It consisted of 229 patients who received warfarin therapy after undergoing mechanical heart valve replacement and maintained a stable INR (INR of 2.0-3.0 for at least three consecutive times). Twenty single-nucleotide polymorphisms including VKORC1, CYP2C9, GATA4, and GATA6 were analyzed. Multivariate logistic regression analysis was employed to investigate the independent risk factors for bleeding complications. To evaluate the potential clinical value of genotyping for preventing bleeding complications in patients with high-risk genotype, the number needed to genotype (NNG) was also calculated. Results: One hundred forty-two patients were included in this study, 21 of whom had bleeding complications. After adjusting covariates, TT genotype carriers of rs13273672 in GATA4 and CC genotype carriers of rs10454095 in GATA6 showed 5.0- (95% CI, 1.6-15.7) and 3.1-fold (95% CI, 1.1-8.7) higher bleeding complications than carriers of C allele and T allele, respectively. NNG for preventing one patient from experiencing bleeding complications in patients with TT genotype of rs13273672 and CC genotype of rs10454095 was 22.2 and 17.5, respectively. Patients with both TT genotype in rs13273672 and CC genotype in rs10454095 showed 8.7-fold (95% CI, 1.7-46.1) higher bleeding complications than those with other genotypes. NNG in patients having both TT genotype in rs13273672 and CC genotype in rs10454095 was calculated to be 40.0. Conclusions: This study showed that GATA4 and GATA6 gene polymorphisms could affect bleeding complications during warfarin treatment in patients with mechanical heart valves.

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.

Association between VEGFA gene polymorphisms and bleeding complications in patients maintaining therapeutic international normalized ratio.

Aim: This study was designed to identify the possible effects of VEGFA polymorphisms on the occurrence of bleeding complications in patients with mechanical heart valves who have achieved therapeutic international normalized ratio (INR). Materials & methods: 13 SNPs of VEGFA were analyzed. Uni- and multi-variate analyses were conducted to identify associations between polymorphisms and bleeding complications. Results & conclusion: Patients with the CC genotype of rs35410204 had an approximately tenfold higher bleeding complication than those with the T allele. For rs866236, patients who had wild-type homozygotes showed an approximately 2.9-fold higher bleeding complication than C allele carriers. This study demonstrated that bleeding complications during warfarin therapy are associated with VEGFA polymorphisms in patients with mechanical heart valves.

Tricuspid annular diameter and right ventricular volume on preoperative cardiac CT can predict postoperative right ventricular dysfunction in patients who undergo tricuspid valve surgery.

BACKGROUND: We investigated the predictive value of preoperative computed tomography (CT)-derived tricuspid annular and right ventricular (RV) parameters for postoperative RV dysfunction in patients undergoing tricuspid valve (TV) surgery. METHODS: We retrospectively reviewed clinical, transthoracic echocardiography (TTE), and CT data of 100 consecutive patients who underwent cardiac CT and subsequently received TV surgery. Preoperative cardiac CT and TTE parameters were analyzed, including TV annulus diameter and RV size. Univariate and multivariate logistic regression analyses were performed to identify significant predictors for postoperative RV dysfunction, both in the entire study population and in the subgroup of patients without preoperative RV dysfunction. RESULTS: Postoperative RV dysfunction occurred in 46% of all patients. In the multivariate logistic regression analysis, longer TV annulus diameter (>29.3 mm/m2 on four-chamber view; (odds ratio [OR] 3.56, 95% confidence interval [CI] 1.13-11.24), larger RV volume (RV end-diastolic volume/body surface area > 128.8 ml/m2) on CT (OR 3.85, 95% CI 1.24-11.98) and presence of preoperative RV dysfunction on TTE (OR 11.96, 95% CI 2.8-50.99) were independent predictors for postoperative RV dysfunction in the entire study population (P < 0.05). Among patients without preoperative RV dysfunction, longer TV annulus diameter (OR 4.02, 95% CI 1.20-13.41) and larger RV volume on CT (OR 6.09, 95% CI 1.87-19.80) were independent predictors for postoperative RV dysfunction (P < 0.05). CONCLUSIONS: Preoperative assessment of cardiac CT imaging-based TV annular diameter and RV volume can provide independent information for predicting postoperative RV dysfunction in patients undergoing TV surgery.

Clinical characteristics and rhythm outcome of catheter ablation of hemodynamically corrected valvular atrial fibrillation.

BACKGROUND: Although the hemodynamic burden and structural substrate contribute to valvular atrial fibrillation (VAF) mechanisms, the role of catheter ablation has rarely been reported. We investigated the clinical characteristics, mapping findings, and long-term rhythm outcomes after catheter ablation of hemodynamically corrected VAF. METHODS: We compared 77 patients with VAF (46.8% male, 52.7±8.8 years old, 46.8% paroxysmal AF, 24.7% with maze procedures) and 2244 patients with non-VAF (NVAF) who underwent catheter ablation. Among the VAF patients, 44 (57.1%) had mechanical valve AF (MV-AF) and 33 (42.9%) underwent a prior mitral valvuloplasty (MVP-AF). We analyzed the catheter ablation rhythm outcomes for MV-AF and MVP-AF. RESULTS: The left atrial (LA) diameter was greater (p<0.001), LA voltage lower (p<0.001), and procedure-related complication rate higher (mainly sinus node dysfunction, p=0.004) for VAF than NVAF. During 70.2±1.8 months of follow-up, the rhythm outcome of VAF did not significantly differ from that of NVAF after catheter ablation (log rank p=0.399), even after excluding patients with maze procedures (log rank p=0.629). The clinical recurrence rates did not differ between the MV-AF and MVP-AF groups (log rank p=0.244), or between patients with prior maze procedures and those without (log rank p=0.651). The main conduction recovery sites of previous maze procedures were the perimitral (84.2%) and cavotricuspid isthmus (84.2%) areas, and recurrence mechanisms were macroreentry (63.2%) and focal/microreentry (26.3%) at scar border zones. CONCLUSIONS: Although hemodynamically corrected VAF was associated with advanced LA remodeling, the rhythm outcome did not significantly differ from that of NVAF after catheter ablation.