RESUMO
BACKGROUND: Atrial fibrillation (AF) ablation with minimally interrupted direct oral anticoagulants (DOACs) may raise a concern about their remaining activity. We tested the residual activity of four different DOACs and its impact on intraprocedural heparinization in patients undergoing AF ablation. METHODS: We measured the anti-factor Χa activity for rivaroxaban, apixaban, and edoxaban, and serum DOAC concentration for rivaroxaban, apixaban, and dabigatran, 24 hours after the last intake in patients undergoing AF ablation treated with standard or reduced doses of DOACs. The heparin requirement during the procedure was also measured. RESULTS: We enrolled 34 patients with rivaroxaban, 35 with apixaban, 32 with edoxaban, and 31 with dabigatran, and among them, 30 were treated with reduced doses. The anti-factor Χa activity was the highest in the apixaban group among the patients with standard doses. The DOAC concentration was paradoxically lower in patients with standard doses than in those with reduced doses among the patients with rivaroxaban (34.3 ± 19.8 vs 56.6 ± 7.7 ng/mL; P = .01) and dabigatran (12.6 ± 10.6 vs 23.4 ± 14.7 ng/mL; P = .03). The total heparin requirement per body surface area had significant correlations with the anti-factor Χa activity (r = -.36) and DOAC concentration (r = -.32). Two different multiple linear regression models (adjusted R2 = 0.56 and 0.6, respectively) revealed that the anti-factor Χa activity (ß = -.28; P = .002) and DOAC concentration (ß = -.38; P < .001) were independent determinants of the total heparin requirement. CONCLUSIONS: Factors determining residual DOAC activity may include its type and dose regimen, and it may influence the heparin requirement during AF ablation.
Assuntos
Fibrilação Atrial , Preparações Farmacêuticas , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Dabigatrana/efeitos adversos , Humanos , Piridonas/uso terapêutico , Rivaroxabana/efeitos adversosRESUMO
BACKGROUND: A common SCN5A polymorphism H558R (c.1673 A > G, rs1805124) improves sodium channel activity in mutated channels and known to be a genetic modifier of Brugada syndrome patients (BrS). We investigated clinical manifestations and underlying mechanisms of H558R in BrS. METHODS AND RESULTS: We genotyped H558R in 100 BrS (mean age 45 ± 14 years; 91 men) and 1875 controls (mean age 54 ± 18 years; 1546 men). We compared clinical parameters in BrS with and without H558R (H558R+ vs. H558R- group, N = 9 vs. 91). We also obtained right atrial sections from 30 patients during aortic aneurysm operations and compared SCN5A expression and methylation with or without H558R. H558R was less frequent in BrS than controls (9.0% vs. 19.2%, P = 0.028). The VF occurrence ratio was significantly lower (0% vs. 29.7%, P = 0.03) and spontaneous type 1 ECG was less observed in H558R+ than H558R- group (33.3% vs. 74.7%, P = 0.01). The SCN5A expression level was significantly higher and the methylation rate was significantly lower in sections with H558R (N = 10) than those without (0.98 ± 0.14 vs. 0.83 ± 0.19, P = 0.04; 0.7 ± 0.2% vs. 1.6 ± 0.1%, P = 0.004, respectively). In BrS with heterozygous H558R, the A allele mRNA expression was 1.38 fold higher than G allele expression. CONCLUSION: The SCN5A polymorphism H558R may be a modifier that protects against VF occurrence in BrS. The H558R decreased the SCN5A promoter methylation and increased the expression level in cardiac tissue. An allelic expression imbalance in BrS with a heterozygous H558R may also contribute to the protective effects in heterozygous mutations.
Assuntos
Síndrome de Brugada/genética , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adulto , Idoso , Metilação de DNA , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismoRESUMO
BACKGROUND: An animal experiment showed that long-term atrial pacing or persistent atrial fibrillation (AF) caused electrical remodeling of the atrioventricular (AV) node. We aimed to test the hypothesis that persistent AF decreases the AV conductivity in human hearts. METHODS AND RESULTS: We retrospectively compared the cardiac electrophysiological properties between patients with paroxysmal AF who underwent catheter ablation (PXAF, N = 254) and those with persistent or longstanding persistent AF (PSAF, N = 213). The PSAF patients were more likely than PXAF patients to have longer atrial-His (AH) (96.3 ± 25.7 vs. 91.3 ± 20.4 milliseconds; P = 0.02) and His-ventricle (HV) (43.1 ± 9.4 vs. 41.2 ± 8.6 milliseconds; P = 0.02) intervals. The AV nodal effective refractory period (ERP) (299.1 ± 74.6 vs. 276.2 ± 58.9 milliseconds; P < 0.001) and Wenckebach cycle length (420.9 ± 80.3 vs. 386 ± 58.6 milliseconds; P < 0.001) were also more prolonged in the PSAF patients. We found a dual AV nodal physiology with a similar frequency in both groups. The AH interval, fast pathway ERP, and Wenckebach cycle length in the PSAF patients were more likely than in the PXAF patients to be prolonged among the patients without dual pathways, while those intergroup differences were never seen among the patients with dual pathways. In subgroup analyses including only PSAF patients, there was no difference in the AV conductivity between the patients with persistent AF and those with longstanding persistent AF. CONCLUSIONS: Persistent AF may cause a mild decrease in the AV nodal function in human hearts. Electrical remodeling may be uncommon if dual AV nodal pathways are present, and its extent may not depend on the duration of persistent AF.
Assuntos
Potenciais de Ação , Fibrilação Atrial/complicações , Nó Atrioventricular/fisiopatologia , Síndrome do Nó Sinusal/etiologia , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Ablação por Cateter , Técnicas Eletrofisiológicas Cardíacas , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Período Refratário Eletrofisiológico , Estudos Retrospectivos , Síndrome do Nó Sinusal/diagnóstico , Síndrome do Nó Sinusal/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Alcohol consumption and oxidative stress are well-known risk factors for developing atrial fibrillation (AF). Single nucleotide polymorphisms (SNPs) of alcohol dehydrogenase (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) genes encoding enzymes of alcohol and reactive aldehyde metabolism, respectively, are prevalent among East Asians. Here, we examined whether these SNPs were associated with AF in Japanese patients. METHODS AND RESULTS: Five hundred seventy-seven Japanese patients with AF undergoing catheter ablation and 1935 controls at Hiroshima University Hospital were studied. Alcohol consumption habits, medical history, electrocardiogram (EKG), electrophysiology and cardiac echocardiography were reviewed. Patients were also genotyped for ALDH2 (rs671) and ADH1B (rs1229984). A significant linear correlation was found between ALDH2 genotype and mean alcohol intake (P = 1.7 × 10-6). Further, ALDH2 (rs671) was associated with AF (P = 7.6 × 10-4, odds ratio [OR] = 0.6). Frequency of the ALDH2 SNP allele A which limits acetaldehyde metabolism was lower in patients with AF (18.8%) than in controls (23.5%). In contrast, we found that the frequencies of the ADH1B SNP genotypes were similar in patients with AF and in controls. Subset analysis among the 182 patients with lone AF and 914 controls (control II) (<60 years of age and without hypertension), both ALDH2 and ADH1B SNPs were significantly associated with AF (P = 0.013, OR = 0.7; P = 0.0007, OR = 1.4, respectively). The frequency of the dysfunctional allele A of ALDH2 was significantly lower and the dysfunctional allele G of ADH1B was significantly higher in patients with lone AF than in control II (ALDH2 A allele frequency = 0.176 vs 0.235, OR = 1.3, P = 0.013, ADH1B SNP G allele frequency = 0.286 vs 0.220, OR = 1.4, P = 0.0007). CONCLUSIONS: When considering all patients enrolled, the dysfunctional ALDH2 allele was negatively associated with AF. When examining a subset of patients with lone AF, the dysfunctional ALDH2 allele was negatively associated with AF and the slower metabolizing ADH1B allele was positively associated with AF. Hence, prolonged metabolic conversion of alcohol to acetaldehyde may be associated with the occurrence of AF in the Japanese and other East Asian populations.
Assuntos
Álcool Desidrogenase/genética , Aldeído-Desidrogenase Mitocondrial/genética , Fibrilação Atrial/etiologia , Variação Genética/genética , Adulto , Idoso , Álcool Desidrogenase/metabolismo , Consumo de Bebidas Alcoólicas , Aldeído-Desidrogenase Mitocondrial/metabolismo , Povo Asiático , Fibrilação Atrial/enzimologia , Fibrilação Atrial/genética , Ecocardiografia , Eletrocardiografia , Ásia Oriental , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
It has been reported that dexmedetomidine (dex) has an impact on the cardiac conduction system and even has potential antiarrhythmic actions. We examined the influence of dex on the cardiac electrophysiological properties and atrial fibrillation (AF) inducibility. Adult paroxysmal AF patients were randomly assigned to receive (N = 107) or not receive (N = 108) dex during cardiac electrophysiological studies. The corrected sinus node recovery time (558 ± 331 vs. 459 ± 260 milliseconds; P = 0.02), Wenckebach cycle length (P < 0.001), atrioventricular nodal effective refractory period (317 ± 76 vs. 252 ± 54 milliseconds; P < 0.001), and atrio-His interval (P < 0.001) were longer in patients with dex than in those without. We tested the induction of repetitive atrial firing (RFA) defined as the occurrence of ≥2 successive atrial activities induced by single premature atrial stimuli to determine the AF inducibility. RFA was seen with a similar proportion (41.1% vs. 44.4%), yet it was evoked at a longer stimulus coupling interval in the dex patients, which was potentially attributed to the longer atrial effective refractory period (237 ± 36 vs. 213 ± 27 milliseconds; P < 0.001) and more prolonged atrial conduction delay seen in the dex group. In conclusion, dex may depress the sinus and atrioventricular nodal function, however, it may not reduce the AF inducibility.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Fibrilação Atrial/fisiopatologia , Função Atrial/efeitos dos fármacos , Dexmedetomidina/farmacologia , Sistema de Condução Cardíaco/efeitos dos fármacos , Nó Sinoatrial/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Idoso , Fibrilação Atrial/induzido quimicamente , Função Atrial/fisiologia , Dexmedetomidina/efeitos adversos , Eletrocardiografia/efeitos dos fármacos , Feminino , Sistema de Condução Cardíaco/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nó Sinoatrial/fisiologiaRESUMO
BACKGROUND: It is uncertain whether rate or rhythm control is more favorable for patients experiencing tachycardia-induced cardiomyopathy (TIC) secondary to rapid atrial fibrillation (AF). METHODS AND RESULTS: We compared the electrophysiological and hemodynamic properties and outcome after AF ablation in 20 patients with a history of decompensated TIC who maintained sinus rhythm or had paroxysmal AF (group 1), 32 with a history of decompensated TIC who had persistent or longstanding persistent AF (group 2), 377 without TIC who had paroxysmal AF (group 3), and 225 without TIC who had persistent or longstanding persistent AF (group 4). The corrected sinus node recovery time was more prolonged in group 2 than in groups 1, 3, or 4 (1,066 ± 946 vs. 416 ± 188, 450 ± 322 and 590 ± 329 milliseconds; P < 0.001, respectively). The mean left atrial pressure in group 2 was greater than that in groups 1, 3, or 4 (13.9 ± 6.5 vs. 7.5 ± 3.1, 8.2 ± 4.1 and 10.8 ± 4.2 mmHg; P < 0.001, respectively). The left ventricular ejection fraction assessed after the recovery from the decompensation was more decreased in group 2 than in group 1; however, it almost returned to normal if sinus rhythm was maintained after the AF ablation in group 2. The presence of a history of TIC did not predict an AF recurrence after the ablation. CONCLUSIONS: Heart rate control during AF without sinus conversion may result in an incomplete cure of TIC, suggesting the advantages of rhythm control with ablation in patients with TIC.
Assuntos
Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Cardiomiopatias/epidemiologia , Cardiomiopatias/cirurgia , Ablação por Cateter/estatística & dados numéricos , Taquicardia Ventricular/epidemiologia , Taquicardia Ventricular/cirurgia , Fibrilação Atrial/diagnóstico , Cardiomiopatias/diagnóstico , Causalidade , Comorbidade , Intervalo Livre de Doença , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Taquicardia Ventricular/diagnóstico , Falha de Tratamento , Resultado do TratamentoRESUMO
AIMS: T-wave alternans (TWA) is an indicator of vulnerability to ventricular arrhythmias and is useful for predicting sudden cardiac death (SCD) in patients with various structural heart diseases. We evaluated whether high levels of time-domain TWA on ambulatory ECG (AECG) are associated with a history of ventricular fibrillation (VF) in Brugada syndrome (BrS) patients. METHODS AND RESULTS: We examined the associations among VF history, family history of SCD, spontaneous type 1 electrocardiogram (ECG), late potentials, VF induction by programmed electrical stimulation, and TWA in 45 BrS patients (44 males; mean age, 45 ± 15 years). TWA analyzed from 24-h AECG recordings using the modified moving average method was positive in 13 of 43 patients (30%). Patients with a history of VF had a significantly higher incidence of a positive TWA test (82% vs. 13%; P < 0.001) and spontaneous type 1 ECG (92% vs. 38%; P = 0.007) than those without VF history. Multivariate analysis indicated that positive TWA (OR 7.217; 95% CI 2.503-35.504; P = 0.002) and spontaneous type 1 ECG (OR 5.530; 95% CI 1.651-34.337; P = 0.020) were closely associated with VF history. Spontaneous type 1 ECG had high sensitivity (92%) but low specificity (63%). Positive TWA was a reliable marker with high sensitivity and specificity (82% and 88%, respectively). CONCLUSION: Elevated time-domain TWA on AECG confirms arrhythmia risk in symptomatic BrS patients without the need for provocative stimuli.
Assuntos
Síndrome de Brugada/complicações , Síndrome de Brugada/fisiopatologia , Eletrocardiografia Ambulatorial , Fibrilação Ventricular/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: The heart failure (HF) "pandemic" is an ongoing critical issue related to the aging population. Among the new heart failure medications, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to provide clinical benefit in HF patients with chronic kidney disease (CKD). However, the efficacy and safety of SGLT2i in old age patients remains uncertain. METHODS: The OSHO-heart (Optimal Solution after Hospitalization in Onomichi for heart failure) is a prospective study of 213 patients aged ≥ 75 years-old hospitalized for acute decompensated HF with stage 3 to 4 CKD. The composite outcomes of HF rehospitalizations or cardiovascular death and the rate of decline in the estimated glomerular filtration rate (eGFR) were compared between the Loop (n = 76), tolvaptan (TLV) (n = 80) and SGLT2i (n = 57) groups, respectively. RESULTS: During follow-up (17.2 months, median), composite of HF rehospitalization or cardiovascular death events occurred in 30 (39.5%) in Loop, 19 (23.8%) in TLV and 8 (14%) in SGLT2i groups, respectively (Log-rank: P = 0.015). A multivariate analysis demonstrated that the continuation of SGLT2i (hazard ratio, 0.41; 95% CI, 0.19 to 0.78; P = 0.022) and an EF < 30% (hazard ratio, 2.19; 95% CI, 1.22 to 3.92; P = 0.009) were independently associated with the composite outcome. The rate of decline in the eGFR was significantly less in TLV and SGLT2i groups than Loop group (-1.64 vs. -1.28 vs. -5.41 ml/min/1.73 m2 per year, P = 0.007, respectively). CONCLUSIONS: SGLT2i therapy might reduce the combined risk of HF hospitalizations or cardiac death and preserve a worsening renal function in old age patients with HF and CKD.
Assuntos
Insuficiência Cardíaca , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Humanos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/complicações , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tolvaptan/uso terapêuticoRESUMO
PURPOSE: Thromboembolic or hemorrhagic complications related to atrial fibrillation (AF) ablation are rare, and thus, it is difficult to compare their frequency across different direct oral anticoagulants (DOACs). We aimed to compare the intra-ablation blood coagulability and post-procedural hemoglobin fall as alternatives to those complications across 4 DOACs. METHODS: We enrolled AF patients younger than 65 years old in 3 cardiovascular centers who skipped a single dose of apixaban, dabigatran, edoxaban, and rivaroxaban, prior to the ablation. Endpoints included the activated clotting time (ACT), heparin requirement during the ablation, and drop in the hemoglobin level 24 h after the procedure. RESULTS: The time-course curves of the ACT differed significantly across the patients with apixaban (N = 113), dabigatran (N = 130), edoxaban (N = 144), and rivaroxaban (N = 81), with its highest level in the dabigatran group (P < 0.001). The average ACT was greater in the dabigatran group than in the other groups (312.3 ± 34, 334.4 ± 44, 308.1 ± 41, and 305.8 ± 34.7 s; P < 0.001). A significant difference was noted in total heparin requirement across the patient groups (3990.2 ± 1167.9, 3890.4 ± 955.3, 4423.8 ± 1051.6, and 3972 ± 978.7 U/m2/h; P < 0.001), with its greatest amount in the edoxaban group. The reduction in the hemoglobin level was similar (- 0.93 ± 0.92, - 0.88 ± 0.79, - 0.89 ± 0.97, - 0.95 ± 1.23 g/dL; P = 0.94). No inter-group difference was noted in the rate of major or minor bleedings (0.9%, 2.3%, 1.4%, and 3.7%; P = 0.51), and no thromboembolic events were encountered. CONCLUSION: A difference in DOACs may have an impact on intra-ablation anticoagulation; however, it may not be on the procedural blood loss in the setting of a single skip.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Preparações Farmacêuticas , Administração Oral , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Dabigatrana , Hemoglobinas , Humanos , RivaroxabanaRESUMO
Pause following incessant tachycardia is often encountered in clinical practice. We encountered a rare arrhythmic condition mimicking tachycardia-bradycardia syndrome. We hereby describe the step-by-step diagnostic process.
RESUMO
BACKGROUND: Atrial fibrillation (AF) ablation with minimally interrupted direct oral anticoagulants (DOACs) predominates, possibly raising concern about their remaining activity during the procedure. We aimed to examine residual activities of 4 different DOACs. METHODS: The serum DOAC concentration and anti-factor Χa activity were measured 3 and 24â¯h after the last intake in patients undergoing AF ablation who were treated with rivaroxaban, apixaban, edoxaban, or dabigatran. RESULTS: The reduction in the apixaban concentration between the 2 blood sampling time points (Nâ¯=â¯32, mean⯱â¯SD, -67.7⯱â¯14.8% [231.6⯱â¯93.1 to 71.9⯱â¯31.8â¯ng/mL]) was smaller than that for rivaroxaban (Nâ¯=â¯28, -83.6⯱â¯10.9% [234.2⯱â¯96.6 to 34.3⯱â¯19.8â¯ng/mL]; Pâ¯<â¯0.001) and dabigatran (Nâ¯=â¯20, -90.7⯱â¯7.3% [135.3⯱â¯68.3 to 12.6⯱â¯10.6â¯ng/mL]; Pâ¯<â¯0.001), with its greatest value measured 24â¯h after the last intake in the apixaban group. The decrease in the anti-factor Χa activity was also smaller in the patients with apixaban (-73.8⯱â¯12.7%) than with rivaroxaban (-87.9⯱â¯7.9%; Pâ¯<â¯0.001) and edoxaban (Nâ¯=â¯22, -81.9⯱â¯15.2%; Pâ¯=â¯0.049), and its remaining activity 24â¯h after the last dose was the highest in the apixaban group. A serum DOAC concentration measured 24â¯h after the last dose of >30â¯ng/mL was seen in 41 (51.3%) patients with rivaroxaban, apixaban, or dabigatran, and it was independently associated with apixaban versus rivaroxaban (odds ratio 5.0; Pâ¯=â¯0.01) and apixaban versus dabigatran (odds ratio 74.0; Pâ¯<â¯0.001). CONCLUSION: The pattern of drug elimination from blood may vary depending on DOACs, and their residual activity may not be negligible even 24â¯h after the last intake.
Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Administração Oral , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) still remains a serious issue. Ca2+ handling has a considerable effect on AF recurrence. The histidine-rich calcium-binding protein (HRC) genetic single nucleotide polymorphism (SNP), rs3745297 (T>G, Ser96Ala), is known to cause a sarcoplasmic reticulum Ca2+ leak. We investigated the association between HRC Ser96Ala and AF recurrence after RFCA in paroxysmal AF (PAF) patients. METHODS AND RESULTS: We enrolled PAF patients who underwent RFCA (N = 334 for screening and N = 245 for replication) and were genotyped for HRC SNP (rs3745297). The patient age was younger and rate of diabetes and hypertension lower in the PAF patients with Ser96Ala than in those without (TT/TG/GG, 179/120/35; 64±10/60±12/59±13 y, P = 0.001; 18.5/ 9.2/8.6%, P = 0.04 and 66.1/50.0/37.1%, P = 0.001, respectively). During a mean 19 month follow-up, 57 (17.1%) patients suffered from AF recurrences. The rate of an Ser96Ala was significantly higher in patients with AF recurrence than in those without in the screening set (allele frequency model: odds ratio [OR], 1.80; P = 0.006). We also confirmed this significant association in the replication set (OR 1.74; P = 0.03) and combination (P = 0.0008). A multivariate analysis revealed that the AF duration, sinus node dysfunction, and HRC Ser96Ala were independent predictors of an AF recurrence (hazard ratio [HR], 1.04, P = 0.037; HR 2.42, P = 0.018; and HR 2.66, P = 0.007, respectively). CONCLUSION: HRC SNP Ser96Ala is important as a new genetic marker of AF recurrence after RFCA.
Assuntos
Fibrilação Atrial/genética , Proteínas de Ligação ao Cálcio/genética , Ablação por Cateter/métodos , Polimorfismo de Nucleotídeo Único , Fibrilação Atrial/patologia , Fibrilação Atrial/terapia , Biomarcadores , Feminino , Seguimentos , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RecidivaRESUMO
Objective The neutrophil-to-lymphocyte ratio (NLR) is an inflammation marker that can be used to detect atrial inflammatory changes, which may contribute to a reduced left atrial (LA) function and thrombosis. Our study aimed to determine whether or not the association of NLR with the LA appendage (LAA) function in relation to thrombogenesis differs from the association with the LA body function in paroxysmal atrial fibrillation (PAF) patients. Methods A total of 183 PAF patients were studied. The LA volume index, mitral flow velocity (A), and mitral annular motion velocity (A') were examined using transthoracic echocardiography. The LAA area, LAA wall motion velocity, and presence of spontaneous echo contrast (SEC) were examined using transesophageal echocardiography. Results The NLR of patients with cerebral embolism was significantly greater than in patients without the disorder. A cut-off point of 2.5 for the NLR had a sensitivity of 71% and a specificity of 74% in predicting cerebral embolism. The patients with an NLR ≥2.5 had a higher CHADS2 score and greater LA volume index or LAA area than those with an NLR <2.5. The NLR was an independent risk factor for SEC and was significantly correlated with the LAA wall motion velocity (r=-0.409) in 153 patients without SEC and with the LAA wall motion velocity and LAA area (r=-0.583, r=0.654, respectively) in 30 patients with SEC, but not with the LA volume index, A, or A' in either group. Conclusion In PAF patients, a high NLR indicates thrombogenesis with a high degree of certainty and is associated with reduced LAA contraction rather than with the LA body function.
Assuntos
Apêndice Atrial/fisiopatologia , Fibrilação Atrial/sangue , Função do Átrio Esquerdo/fisiologia , Linfócitos/metabolismo , Neutrófilos/metabolismo , Trombose/etiologia , Idoso , Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/complicações , Biomarcadores , Ecocardiografia/métodos , Ecocardiografia Transesofagiana , Feminino , Átrios do Coração/fisiopatologia , Hemodinâmica , Humanos , Embolia Intracraniana/complicações , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e Especificidade , Trombose/complicaçõesRESUMO
INTRODUCTION: The single nucleotide polymorphism (SNP) rs2106261 in the transcription factor gene ZFHX3 (16q22), a major regulator of inflammation, has been reported linking to atrial fibrillation (AF) by genome-wide association studies. Inflammation is known to be a strong predictor of atrial fibrillation recurrence after ablation, so we examined the association of the ZFHX3 SNP rs2106261 to inflammation marker expression and recurrence after AF ablation. METHODS: We genotyped ZFHX3 SNP rs2106261 and compared the minor (T) allele frequency between 362 paroxysmal AF (PAF) patients underwent pulmonary vein isolation (PVI) and 627 non-AF controls. We also analyzed associations between ZFHX3 SNP rs2106261 genotype and recurrence rate after pulmonary vein isolation and the inflammation markers. RESULTS: The minor (T) allele frequency of the ZFHX3 SNP rs2106261 was significantly higher in AF patients than non-AF controls (odds ratio 1.52, p = 2.2×10-5). Multivariable analysis revealed that the minor allele (T) decreased AF recurrence rate after pulmonary vein isolation (hazard ratio 0.53, p = 0.04). Further, neutrophil/lymphocyte (N/L) ratio, C-reactive protein (CRP), and interleukin-6 (IL-6) expression levels were lower in PAF patients with the ZFHX3 SNP rs2106261 minor allele (TT+TC) than in CC patients (N/L ratio: CC 2.22 ± 0.08, TT+TC 1.98 ± 0.06, p = 0.018; CRP: CC 0.103 ± 0.009 mg/dl, TT+TC 0.076 ±0.007 mg/dl, p = 0.016; IL-6: CC 60.3 ± 3.0 pg/ml, TT+TC 52.8 ± 2.3 pg/ml, p = 0.04). CONCLUSIONS: The ZFHX3 SNP rs2106261 minor allele is associated with lower AF recurrence rate after pulmonary vein isolation. Low baseline inflammation conferred by this allele may reduce AF recurrence risk.
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Fibrilação Atrial/genética , Fibrilação Atrial/cirurgia , Ablação por Cateter , Proteínas de Homeodomínio/genética , Inflamação/genética , Veias Pulmonares/cirurgia , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Recidiva , Estudos RetrospectivosRESUMO
Genome-wide association studies have reported a strong association of the single nucleotide polymorphism (SNP) rs6817105 (T > C) on chromosome 4q25 with atrial fibrillation (AF), but phenotype alterations conferred by this SNP have not been described. We genotyped SNP rs6817105 and examined the relationships among rs6817105 genotype, clinical characteristics, echocardiographic parameters, and electrophysiological parameters in 574 AF patients and 1,554 non-AF controls. Further, multiple microRNAs (miRNAs) are reported to be involved in atrial remodeling and AF pathogenesis, so we investigated relationships between rs6817105 genotype and serum concentrations of 2555 miRNAs. The rs6817105 minor allele frequency was significantly higher in AF patients than non-AF controls (66% vs. 47%, odds ratio 2.12, p = 4.9 × 10-26). Corrected sinus node recovery time (CSRT) was longer and left atrial volume index (LAVI) was larger in AF patients with the rs6817105 minor allele than patient non-carriers (CSRT: CC 557 ± 315 ms, CT 486 ± 273 ms, TT 447 ± 234 ms, p = 0.001; LAVI: CC 43.6 ± 12.1, CT 42.4 ± 13.6, TT 39.8 ± 11.6, p = 0.030). There were no significant differences between rs6817105 genotype and the serum concentrations of miRNAs. These findings strongly implicate rs6817105 minor allele in sinus node dysfunction and left atrial enlargement.
Assuntos
Fibrilação Atrial/genética , Cromossomos Humanos Par 4 , Loci Gênicos , Genótipo , Átrios do Coração/patologia , Síndrome do Nó Sinusal/genética , Idoso , Fibrilação Atrial/patologia , Ecocardiografia , Eletrocardiografia , Feminino , Frequência do Gene , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Síndrome do Nó Sinusal/patologiaRESUMO
BACKGROUND: Tachycardia-induced cardiomyopathy (TIC) is a reversible cardiomyopathy induced by tachyarrhythmia, and the genetic background of the TIC is not well understood. The hyperpolarization-activated cyclic nucleotide-gated channel gene HCN4 is highly expressed in the conduction system where it is involved in heart rate control. We speculated that the HCN4 gene is associated with TIC. METHODS: We enrolled 930 Japanese patients with atrial fibrillation (AF) for screening, 350 Japanese patients with AF for replication, and 1635 non-AF controls. In the screening AF set, we compared HCN4 single-nucleotide polymorphism genotypes between AF subjects with TIC (TIC, n=73) and without TIC (non-TIC, n=857). Of 17 HCN4 gene-tag single-nucleotide polymorphisms, rs7172796, rs2680344, rs7164883, rs11631816, and rs12905211 were significantly associated with TIC. Among them, only rs7164883 was independently associated with TIC after conditional analysis (TIC versus non-TIC: minor allele frequency, 26.0% versus 9.7%; P=1.62×10-9; odds ratio=3.2). RESULTS: We confirmed this association of HCN4 single-nucleotide polymorphism rs7164883 with TIC in the replication set (TIC=41 and non-TIC=309; minor allele frequency, 28% versus 9.9%; P=1.94×10-6; odds ratio=3.6). The minor allele frequency of rs7164883 was similar in patients with AF and non-AF controls (11% versus 10.9%; P=0.908). CONCLUSIONS: The HCN4 gene single-nucleotide polymorphism rs7164883 may be a new genetic marker for TIC in patients with AF.
Assuntos
Fibrilação Atrial , Cardiomegalia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Proteínas Musculares , Polimorfismo Genético , Canais de Potássio , Taquicardia , Fibrilação Atrial/complicações , Fibrilação Atrial/genética , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Cardiomegalia/etiologia , Cardiomegalia/genética , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Canais de Potássio/genética , Canais de Potássio/metabolismo , Taquicardia/complicações , Taquicardia/genética , Taquicardia/metabolismo , Taquicardia/patologiaRESUMO
BACKGROUND: Radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) refractory to medical therapy remains controversial in patients with hypertrophic cardiomyopathy (HCM); the acute effects on the direct left atrial (LA) pressure are not completely understood. METHODS: We consecutively studied patients with HCM (n=15) and without HCM (NHCM, n=106) who underwent extensive encircling pulmonary vein isolation for drug-refractory AF. We compared clinical parameters, echocardiographic parameters, electrophysiological parameters, LA pressures using hemodynamic catheterization and recurrence rate in both groups. RESULTS: The LA volume index was significantly higher (51.9±13.6 mL/m2 vs. 41.6±12.7 mL/m2, p=0.02) in the HCM group than the NHCM group. The pre-ablation mean LA pressure was significantly higher in the HCM group than the NHCM group. Among the AF patients, the mean LA pressure decreased more significantly in the HCM group than the NHCM group (post-ablation minus pre-ablation pressures: 4.2±3.7 mmHg vs. 0.9±4.1 mmHg, p=0.03). The early recurrence rate (within 30 days after ablation) tended to be higher in the HCM group than the NHCM group (20% vs. 5.7%, p=0.08), but the rates of late recurrences (>30 days after ablation) were similar (13.3% vs. 7.6%, p=0.83). Discontinuation of antiarrhythmic drugs occurred at rates of 13% and 62% in the HCM and NHCM groups, respectively (p<0.001). CONCLUSIONS: The LA pressure in the HCM group decreased immediately after AF RFCA. Patients with HCM and drug-refractory AF may benefit from RFCA.
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BACKGROUND: The impact of subclinical hypothyroidism on the cardiovascular risk is still debated. We aimed to measure the relationship between subclinical hypothyroidism and the left atrial (LA) pressure. METHODS: The LA pressures and thyroid function were measured in consecutive patients undergoing atrial fibrillation (AF) ablation, who did not have any known heart failure, structural heart disease, or overt thyroid disease. RESULTS: Subclinical hypothyroidism (4.5≤ thyroid-stimulating hormone <19.9 mIU/L) was present in 61 (13.0%) of the 471 patients included. More subclinical hypothyroidism patients than euthyroid patients (55.7% vs 40.2%; P=0.04).'euthyroid patients had persistent or long-standing persistent AF (55.7% vs 40.2%; P = 0.04). The mean LA pressure (10.9 ± 4.7 vs 9.1 ± 4.3 mmHg; P = 0.002) and LA V-wave pressure (17.4 ± 6.5 vs 14.3 ± 5.9 mmHg; P < 0.001) were, respectively, higher in the patients with subclinical hypothyroidism than in the euthyroid patients. After an adjustment for potential confounders, the LA pressures remained significantly higher in the subclinical hypothyroidism patients. A multiple logistic regression model showed that subclinical hypothyroidism was independently associated with a mean LA pressure of >18 mmHg (odds ratio 3.94, 95% CI 1.28 11.2; P = 0.02). CONCLUSIONS: Subclinical hypothyroidism may increase the LA pressure in AF patients.
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BACKGROUND: Risk stratification for ventricular fibrillation (VF) in patients with Brugada syndrome (BrS) remains controversial. OBJECTIVE: The purpose of this study was to construct a novel prediction model for VF risk in BrS patients using noninvasive parameters. METHODS: A total of 143 Japanese BrS patients with VF (n = 35) and without VF (n = 108) were retrospectively enrolled. We built a logistic regression model predicting VF occurrence and evaluated it by cross-validation. RESULTS: Frequencies of history of syncope and spontaneous type 1 ECG, r-J interval in V1, QRS duration in V6, and LAS40, Tpeak-Tend dispersion, and max T-wave alternans were significantly associated with VF occurrence in univariate analyses. The history of syncope, r-J interval in V1, QRS duration in V6, and Tpeak-Tend dispersion were identified as independent predictors by multivariate logistic regression analysis. The predictive model was constructed using all these parameters with good discrimination of VF occurrence (area under the curve 0.869 with 97.1% sensitivity and 65.7% specificity). The area under the curve based on leave-one-out cross-validation was 0.845, with 97.1% sensitivity and 63.0% specificity suggesting good performance of the model. Retrospective survival analysis revealed that the cumulative VF event rate was significantly higher in patients at high risk than in those with low risk using the log rank test (P = 2.97 × 10(-8)). Notably, no BrS patient below the cutoff value developed a subsequent VF event. CONCLUSION: This novel prediction method may effectively assesses VF risk in BrS patients, especially when determining implantable cardioverter-defibrillator placement for asymptomatic BrS patients.