RESUMO
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.
Assuntos
Fibrilação Atrial , Infarto do Miocárdio , Anticoagulantes/efeitos adversos , Predisposição Genética para Doença , Genótipo , Valvas Cardíacas , Humanos , Nucleotídeos , Polimorfismo de Nucleotídeo Único , Fator de Crescimento Transformador beta1/genética , Varfarina/efeitos adversosRESUMO
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.
Assuntos
Valvopatia Aórtica/cirurgia , Próteses Valvulares Cardíacas/estatística & dados numéricos , Procedimentos Cirúrgicos sem Sutura/métodos , Idoso , Idoso de 80 Anos ou mais , Valvopatia Aórtica/mortalidade , Bioprótese/estatística & dados numéricos , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Marca-Passo Artificial/estatística & dados numéricos , Complicações Pós-Operatórias , Pontuação de Propensão , República da Coreia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
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.
Assuntos
Hemorragia/induzido quimicamente , Fator 4 Nuclear de Hepatócito/genética , Mutação , Polimorfismo de Nucleotídeo Único , Varfarina/efeitos adversos , Idoso , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Próteses Valvulares Cardíacas , Hemorragia/genética , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Vitamina K Epóxido Redutases/genéticaRESUMO
BACKGROUND: Atrial fibrillation (AF) can occur even after the correction of mitral valve (MV) pathology in patients who have pre-operative sinus rhythm and undergo MV surgery. However, the factors associated with the occurrence of AF after MV surgery are still unclear. The aim of this retrospective study was to investigate the factors determining the occurrence of permanent AF after MV surgery in patients with preoperative sinus rhythm who underwent MV surgery. METHODS: Four hundred and forty-two patients (mean age 46 ± 12, 190 men) who underwent MV surgery and sinus rhythm were investigated retrospectively. Transthoracic echocardiography was performed before and after MV surgery at the time of dismissal. RESULTS: Permanent post-operative AF occurred in 81 (18%) patients even after successful MV surgery and preoperative sinus rhythm. It was more common in rheumatic etiology, a presence of mitral stenosis, lower pre- and post-operative left ventricular ejection fraction, higher post-operative mean diastolic pressure gradient across mitral prosthesis, larger post-operative left atrial volume index (LAVI) and lesser degrees of reduction in LAVI after surgery. In multiple regression analysis, post-operative LAVI was found to be an independent predictor for occurrence of AF. Post-operative LAVI > 39 ml/m2 was the cut-off value for best prediction of new onset permanent AF (sensitivity: 79%, AUC: 0.762, SE: 0.051, p < 0.001). CONCLUSION: New-onset permanent post-operative AF is not uncommon, even after successful MV surgery despite pre-operative sinus rhythm. Larger post-operative LAVI was an independent predictor for the occurrence of AF.
Assuntos
Fibrilação Atrial/diagnóstico por imagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Átrios do Coração/diagnóstico por imagem , Doenças das Valvas Cardíacas/cirurgia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Tamanho do Órgão , Adulto , Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Ecocardiografia , Feminino , Átrios do Coração/fisiopatologia , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: This study investigated the consequences of recurrent mitral regurgitation (MR) after mitral valve (MV) repair in patients with degenerative MR and risk factors for recurrence.MethodsâandâResults:From January 1990 to December 2015, 792 patients underwent MV repair due to degenerative MR. Recurrent MR was defined as moderate-to-severe MR on follow-up echocardiography. Mean follow-up duration was 8.71±5.58 years. During the follow-up period, MR recurred in 133 (16.8%) patients, and the MR recurrence-free rate at 20 years was 77.5±2.0%. In the recurrence group, the degree of MR decreased in 8 (6.0%) patients and was aggravated in 46 (34.6%) patients. Recurrent MR was associated with increased mortality and adverse left ventricular (LV) remodeling. Independent risk factors for MR recurrence were MV repair performed before 2000, preoperative atrial fibrillation, high LV end-diastolic dimension (LVEDD), prolapse of the isolated anterior leaflet or multiple segments, and absence of ring annuloplasty. Predictors of MR progression were high LVEDD and repair without artificial chordae implantation. CONCLUSIONS: Recurrent MR after MV repair in patients with degenerative MR showed a tendency to progress and was associated with increased mortality and adverse LV remodeling. Early referral for MV repair before development of atrial fibrillation and LV enlargement may reduce the risk of MR recurrence. Moreover, artificial chordae implantation and ring annuloplasty may assure the long-term durability of MV repair.
Assuntos
Insuficiência da Valva Mitral/patologia , Valva Mitral/cirurgia , Recidiva , Adulto , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/mortalidade , Resultado do Tratamento , Remodelação VentricularRESUMO
A possible association between the combination of genetic variations in hepatocyte nuclear factor 4α (HNF4α) and constitutive androstane receptor (CAR) and the stable doses of warfarin was examined in patients from the Ewha-Severance Treatment (EAST) Group of Warfarin. Around 42.5% of the overall interindividual variability in warfarin dose requirements was explained by the multivariate regression model; the vitamin K epoxide reductase complex 1 (VKORC1) genotype accounted for 29.6%, the cytochrome P450 (CYP) 2C9 genotype for 4.3%, age for 3.6%, the CYP4F2 genotype for 3.3%, and CAR/HNF4α (rs2501873/rs3212198) for 1.7%. Our results showed that the combination of CAR and HNF4α genotypes could be determinants of stable warfarin doses.
Assuntos
Citocromo P-450 CYP2C9/genética , Sistema Enzimático do Citocromo P-450/genética , Fator 4 Nuclear de Hepatócito/genética , Receptores Citoplasmáticos e Nucleares/genética , Vitamina K Epóxido Redutases/genética , Anticoagulantes/uso terapêutico , Biomarcadores Farmacológicos , Receptor Constitutivo de Androstano , Família 4 do Citocromo P450 , Relação Dose-Resposta a Droga , Feminino , Genótipo , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Varfarina/uso terapêuticoRESUMO
PURPOSE: NAD(P)H dehydrogenase, encoded by NAD(P)H quinone oxidoreductase 1 (NQO1), is an enzyme that catalyzes the reduction of quinones, including vitamin K. Given its potential role in vitamin K metabolism, this study aimed to investigate the effects of NQO1 polymorphisms on stable warfarin doses. METHODS: We tested a possible effect of gene polymorphisms on variability in warfarin response using 206 Korean patients with mechanical cardiac valves. Single nucleotide polymorphisms (SNPs) of NQO1 with a minor allele frequency of at least 15% were included. Also, genotypes of vitamin K epoxide reductase complex subunit 1 (VKORC1), cytochrome P450 (CYP) 2C9, CYP4F2, gamma-glutamyl carboxylase (GGCX), and GATA4 were determined. RESULTS: NQO1 rs1800566 (C>T) and rs10517 (C>T) were significantly associated with stable warfarin doses. Variant homozygote carriers required lower stable warfarin doses than those with wild-type C allele in rs1800566 (4.85 ± 1.61 vs. 5.61 ± 1.94 mg; p = 0.033), whereas patients with wild homozygote required lower doses than those with T allele in rs10517 (5.11 ± 1.73 vs. 5.75 ± 1.98 mg; p = 0.017). Similar results were obtained from stratified analysis using VKORC1 variant homozygote carriers in both SNPs. Multivariate analysis showed that rs10517 (C>T) increased contribution of gene variations to the overall warfarin dose variability from 42.5 to 43.8%. CONCLUSION: Our results demonstrate that NQO1 gene polymorphisms influence stable warfarin doses in Korean patients.
Assuntos
NAD(P)H Desidrogenase (Quinona)/genética , Varfarina/administração & dosagem , Varfarina/farmacocinética , Fatores Etários , Idoso , Índice de Massa Corporal , Citocromo P-450 CYP2C9/genética , Sistema Enzimático do Citocromo P-450/genética , Família 4 do Citocromo P450 , Dipeptidases/genética , Feminino , Fator de Transcrição GATA4/genética , Frequência do Gene , Genótipo , Próteses Valvulares Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , República da Coreia , Fatores Sexuais , Vitamina K Epóxido Redutases/genéticaRESUMO
BACKGROUND: This study aimed to explore whether echocardiographic measurements during the early postoperative period can predict persistent left ventricular systolic dysfunction (LVSD) after aortic valve surgery in patients with chronic aortic regurgitation (AR). METHODS: We prospectively recruited 54 patients (59 ± 12 years) with isolated chronic severe AR who subsequently underwent aortic valve surgery. Standard transthoracic echocardiography was performed before the operation, during the early postoperative period (≤2 weeks), and then 1 year after the surgery. RESULTS: Twelve patients with preoperative LVSD demonstrated LVSD at early after the surgery. Of the 42 patients without LVSD at preoperative echocardiography, 15 patients (36%) developed early postoperative LVSD after surgical correction. All 27 patients without LVSD at early postoperative echocardiography maintained LV function at 1 year after surgery. In the other 27 patients with postoperative LVSD, 17 patients recovered from LVSD and 10 patients did not at 1 year after surgery. Multiple logistic analysis demonstrated that postoperative left atrial volume index (LAVI) was the only independent predictor for persistent LVSD at 1 year after surgery in patients with postoperative LVSD (OR 1.180, 95% CI, 1.003-1.390, P = 0.046). The optimal LAVI cutoff value (>34.9 mL/m(2) ) had a sensitivity of 80% and a specificity of 88% for the prediction of persistent LVSD. CONCLUSION: Prevalence of early postoperative LVSD was relatively high, even in the patients without LVSD at preoperative echocardiography. Postoperative LAVI could be useful to predict persistent LVSD after aortic valve surgery in patients with early postoperative LVSD.
Assuntos
Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/cirurgia , Anuloplastia da Valva Cardíaca/efeitos adversos , Átrios do Coração/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Doença Crônica , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Período Pós-Operatório , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery. Associations between the time interval (TI) from preoperative coronary angiography (CAG) to cardiac surgery have been investigated, although with conflicting results. METHODS: We evaluated data collected from a retrospective review of consecutive patients who underwent preoperative CAG and heart valve surgery at our institution between September 2008 and February 2013. A total of 426 patients met the study criteria. Patients were divided into two groups according to the length of time between preoperative CAG and valve surgery: within one day (group A) or longer than one day (group B). Logistic regression was applied to analyze the relationships between TI and postoperative AKI. RESULTS: Of 426 patients, 140 (33%) underwent CAG on preoperative day 1, while 286 (67%) underwent CAG on preoperative day 2 or sooner. AKI occurred in 19 (13.6%) patients in group A and in 35 (12.2%) patients in group B (p = 0.70). CAG on preoperative day 1 was not associated an increased risk of AKI relative to CAG on preoperative day 2 or sooner (p = 0.49; odds ratio, 1.26; 95% CI, 0.66 to 2.41). CONCLUSIONS: Preoperative CAG within one day of elective heart valve surgery is not associated with an increase in postoperative AKI in patients with normal renal function.
Assuntos
Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Procedimentos Cirúrgicos Cardíacos , Angiografia Coronária/efeitos adversos , Procedimentos Cirúrgicos Eletivos , Valvas Cardíacas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pré-Operatório , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Fatores de TempoRESUMO
BACKGROUND AND AIM OF THE STUDY: The study aim was to identify adequate therapeutic ranges of the International Normalized Ratio (INR) in Korean patients receiving warfarin after prosthetic mechanical heart valve replacement. METHODS: Retrospective chart reviews were conducted of 818 patients for a total follow up period of 8,100 patient-years; all details of major complication events of thromboembolism and bleeding were recorded. The INR-incidence of complication curve was plotted, and an adequate INR determined from the intersections of 95% confidence interval (CI) curves of complication rates to ensure the lowest incidences of both thromboembolic and bleeding complications. An analysis of a subgroup of patients with atrial fibrillation (AF) was performed to evaluate the complication occurrence. RESULTS: A total of 69 complications occurred, of which 36 were thromboembolic events and 33 were bleeding. The adequate ranges of INR were determined as: 2.0-2.5 for patients with aortic or mitral valve replacement; 2.1-2.6 for those with aortic plus mitral valve replacement; and 2.3-2.8 for those with tricuspid valve replacement with or without other valves. It has been shown that, by keeping the INR levels within these therapeutic ranges, complication risks could be significantly reduced by up to 51%. The overall incidence of complications was increased if the patients had AF (hazards risk (HR) = 1.27, 95% CI = 1.05-1.52). CONCLUSION: The study results may provide evidence for the application of low-intensity warfarin therapies in Asian patients, including Koreans. In addition, the method of determining adequate INR levels by using INR-incidence of complications curves might be employed in many clinical settings.
Assuntos
Anticoagulantes/administração & dosagem , Próteses Valvulares Cardíacas/efeitos adversos , Tromboembolia/prevenção & controle , Varfarina/administração & dosagem , Adulto , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estudos Retrospectivos , Tromboembolia/etiologiaRESUMO
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.
RESUMO
BACKGROUND: Recently, a single nucleotide polymorphism of CYP4F2 (rs2108622) was reported to have a significant relationship with the stable warfarin dose. However, the underlying mechanism of CYP4F2 effects on the stable warfarin dose has not been studied. This study aimed to examine the effects of cytochrome P450 (CYP) 4F2 gene on warfarin clearance and sensitivity in Korean patients with mechanical heart valves. METHODS: One hundred ninety-one patients with mechanical heart valves who were on anticoagulation therapy with warfarin and maintained international normalized ratio levels of 2-3 for 3 consecutive times were followed up, retrospectively. Warfarin enantiomer concentrations were determined by a validated high-performance liquid chromatography method. Genotypes of vitamin K epoxide reductase complex subunit 1, CYP2C9, CYP2C19, CYP4F2, human microsomal epoxide hydroxylase, calumenin, and γ-glutamyl carboxylase were determined. RESULTS: From multiple linear regression models, vitamin K epoxide reductase complex subunit 1, CYP2C9, CYP4F2, and age were found to have significant effects on warfarin stable dose. The stable warfarin daily doses of patients with the CC, CT, and TT genotypes in the CYP4F2 gene were 5.34 ± 2.04, 5.33 ± 1.64, and 6.55 ± 2.12 mg, respectively. The higher dose requirements in patients with TT alleles in CYP4F2 were attributable to a low warfarin sensitivity (international normalized ratio/warfarin plasma concentration); the warfarin sensitivity in CC, CT, and TT genotypes was 2.1 ± 1.2, 1.0 ± 0.4, and 0.8 ± 0.6, respectively. The similarity between the dose requirements of patients with CT and CC alleles was explained through the combined result of warfarin sensitivity and clearance outcomes. Apparent plasma (S)- and (R)-warfarin clearances were found to be 37.7% and 34.1% lower in CT genotype patients than in CC genotype patients, respectively. CONCLUSIONS: The dose variability in CYP4F2 genotypes was attributable to both warfarin clearance and sensitivity differences.
Assuntos
Povo Asiático/genética , Sistema Enzimático do Citocromo P-450/genética , Próteses Valvulares Cardíacas , Polimorfismo de Nucleotídeo Único/genética , Varfarina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/etnologia , Família 4 do Citocromo P450 , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Taxa de Depuração Metabólica/fisiologia , Pessoa de Meia-Idade , República da Coreia/etnologiaRESUMO
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.
RESUMO
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.
RESUMO
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.
Assuntos
Previsões , Anuloplastia da Valva Mitral/efeitos adversos , Insuficiência da Valva Mitral/cirurgia , Estenose da Valva Mitral/etiologia , Valva Mitral/cirurgia , Complicações Pós-Operatórias , Pontuação de Propensão , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico , Estenose da Valva Mitral/fisiopatologia , Estenose da Valva Mitral/cirurgia , Reoperação , Estudos Retrospectivos , Fatores de RiscoRESUMO
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.
RESUMO
Mesenchymal stem cells (MSCs) therapy has limitations due to the poor viability of MSCs after cell transplantation. Integrin-mediated adhesion is a prerequisite for cell survival. As a novel anti-death strategy to improve cell survival in the infarcted heart, MSCs were genetically modified to overexpress integrin-linked kinase (ILK). The survival rate of ILK-transfected MSCs (ILK-MSCs) was augmented by about 1.5-fold and the phosphorylation of ERK1/2 and Akt in ILK-MSCs were increased by about three and twofold, respectively. ILK-MSCs demonstrated an increase of twofold in the ratio of Bcl-2/Bax and inhibited caspase-3 activation, compared with hypoxic MSCs. The adhesion rate of ILK-MSCs also had a 32.2% increase on the cardiac fibroblast-derived three-dimensional matrix and ILK-MSCs showed higher retention by about fourfold compared to unmodified MSCs. Six animals per group were used for the in vivo experiments analyzed at 1 week after occlusion of the left coronary artery. ILK-MSC transplanted rats had a 12.0% +/- 3.1% smaller infarct size than MSC-treated rats after ligation of left anterior descending coronary artery. Transplantation of ILK-MSCs not only led to a 16.0% +/- 0.4% decrease in the fibrotic heart area, but also significantly reduced the apoptotic positive index by two-thirds when compared with ligation only. The mean microvessel count per field in the infarcted myocardium of ILK-MSCs group was increased relative to the sham group and MSCs group. In conclusion, the ILK gene transduction of MSCs further assisted cell survival and adhesion, and improved myocardial damage when compared with MSC only after transplantation.
Assuntos
Hipóxia Celular/genética , Sobrevivência de Enxerto/genética , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Isquemia Miocárdica/terapia , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Apoptose/fisiologia , Western Blotting , Adesão Celular/genética , Marcação In Situ das Extremidades Cortadas , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Isquemia Miocárdica/patologia , Engenharia de Proteínas , Proteínas Serina-Treonina Quinases/genética , Ratos , Ratos Sprague-Dawley , Transdução GenéticaRESUMO
BACKGROUND: Aortic valve replacement (AVR) improves left ventricular (LV) systolic function in patients with chronic aortic regurgitation (AR). The objective of this study is to determine predictors for normalization of impaired LV systolic function after valve replacement for chronic AR. METHODS AND RESULTS: Between 1997 and 2007, 171 patients underwent AVR for severe chronic AR. Of these patients, 79 patients with LV systolic dysfunction or severe LV dilatation preoperatively, who were evaluated by echocardiography at predischarge and early follow up (mean, 6 months) were examined. The mean preoperative ejection fraction was 49%. The mean LV end-systolic and end-diastolic dimensions were 52.32 ± 8.35 mm and 69.59 ± 7.80 mm, respectively. In the early follow up, 62 of 79 patients exhibited restored normal LV function. LV end-systolic dimension and LV end-diastolic dimension were significantly decreased early after AVR (52.32 ± 8.35 mm vs 37.82 ± 6.88 mm, and 69.59 ± 7.80 mm vs 51.55 ± 6.40 mm, respectively). Operative mortality was 3.7%. Multivariate stepwise regression analysis revealed that preoperative indexed LV end-systolic and end-diastolic dimensions were independent predictors of restored LV systolic function. The sensitivity and specificity in predicting normalization of LV function were 88% and 92% for indexed LVESD <35.32 mm/m(2) and 71% and 86% for indexed LVEDD <44.42 mm/m(2). CONCLUSIONS: In patients who received a valve replacement for chronic AR, smaller indexed LV systolic and diastolic dimensions were associated with early restoration of LV systolic function.
Assuntos
Insuficiência da Valva Aórtica/cirurgia , Ecocardiografia Doppler , Implante de Prótese de Valva Cardíaca , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Adulto , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/mortalidade , Insuficiência da Valva Aórtica/fisiopatologia , Doença Crônica , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Modelos de Riscos Proporcionais , Recuperação de Função Fisiológica , República da Coreia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Volume Sistólico , Sístole , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
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.
Assuntos
Aorta/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Insuficiência da Valva Aórtica/etiologia , Implante de Prótese Vascular/efeitos adversos , Complicações Pós-Operatórias , Dissecção Aórtica/diagnóstico , Aorta/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/cirurgia , Progressão da Doença , Ecocardiografia Transesofagiana/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
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.