Minor allele of GJA1 gene polymorphism is associated with higher heart rate during atrial fibrillation.

Atrial fibrillation (AF) tachycardia causes heart failure and requires more attention. The genetic background of individual heart rate (HR) variations during AF are unclear. We hypothesized that HR-associated single nucleotide polymorphisms (SNPs) reported in Genome-Wide Association Studies (GWAS) are also associated with HR during AF. We enrolled patients with persistent AF (311 for screening and 146 for replication) who underwent AF ablation and were genotyped for the 21 h-associated SNPs reported in GWAS. The patients underwent 24-h Holter monitoring before AF ablation and electrophysiological study after AF ablation during sinus rhythm. Only the GJA1 SNP rs1015451 (T>C) was significantly associated with total HR (TT 110,643 ± 17,542 beats/day, TC 116,350 ± 19,060 beats/day, CC 122,163 ± 25,684 beats/day, P = 8.5 × 10-4). We also confirmed this significant association in the replication set. The intra-atrial conduction was faster in AF patients with the GJA1 minor allele than in those without it. Multivariate analysis revealed the presence of a GJA1 SNP rs1015451 additive model, female gender, lower left ventricular ejection fraction, and higher 1:1 atrioventricular nodal conduction were independently associated with higher HR during AF. The GJA1 SNP might be a new genetic marker for AF tachycardia.

Remaining activity of temporary interrupted direct oral anticoagulants and its impact on intra-ablation heparinization in patients with atrial fibrillation: Comparisons across four drugs and two dose regimens.

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.

Increased Urinary Liver-Type Fatty Acid-Binding Protein Level Predicts Major Adverse Cardiovascular Events in Patients With Hypertension.

BACKGROUND: Urinary liver-type fatty acid-binding protein (L-FABP) has been known as a potential biomarker for acute kidney injury. It has also been suggested to have an effective predictive value for cardiovascular mortality in patients with diabetes or critically ill condition. Therefore, this study aimed to examine the ability of urinary L-FABP in predicting mid-term cardiovascular morbidity and mortality in patients with hypertension. METHODS: Urinary L-FABP levels in stable outpatients without diabetes who were treated with antihypertensive drugs were measured, and a 5-year follow-up was planned. The primary end-point was a combination of acute heart failure requiring hospitalization, myocardial infarction, stroke, and cardiovascular death. The secondary end-point was kidney disease progression defined as a relative decline in the estimated glomerular filtration rate of ≥30% from the baseline. RESULTS: A total of 197 patients were recruited. Primary and secondary end-points occurred in 24 (12.2%) and 42 (21.3%) patients, respectively, during a median follow-up of 5.7 years. Patients with urinary L-FABP levels higher than the upper limit (8.4 µg/g creatinine) were more likely to reach the primary (30.43% vs. 9.77%; P = 0.003) and secondary end-points (56.52% vs. 16.67%; P < 0.001) than those with urinary L-FABP levels within the normal limits. Urinary L-FABP level was independently associated with both primary (hazard ratio (HR) 1.21; P = 0.03) and secondary end-points (HR 1.19; P = 0.02). CONCLUSIONS: This study demonstrated that increased urinary L-FABP levels may predict adverse cardiovascular events and renal dysfunction progression even among stable nondiabetic patients with hypertension.

Predicting atrial fibrillation using a combination of genetic risk score and clinical risk factors.

BACKGROUND: Atrial fibrillation (AF) has a genetic basis, and environmental factors can modify its actual pathogenesis. OBJECTIVE: The purpose of this study was to construct a combined risk assessment method including both genetic and clinical factors in the Japanese population. METHODS: We screened a cohort of 540 AF patients and 520 non-AF controls for single nucleotide polymorphisms (SNPs) previously associated with AF by genome-wide association studies. The most strongly associated SNPs after propensity score analysis were then used to calculate a weighted genetic risk score (WGRS). We also enrolled 1018 non-AF Japanese subjects as a validation cohort and monitored AF emergence over several years. Finally, we constructed a logistic model for AF prediction combining WGRS and clinical risk factors. RESULTS: We identified 5 SNPs (in PRRX1, ZFHX3, PITX2, HAND2, and NEURL1) associated with AF after Bonferroni correction. There was a 4.92-fold difference in AF risk between the highest and lowest WGRS calculated using these 5 SNPs (P = 2.32 × 10-10). Receiver operating characteristic analysis of WGRS yielded an area under the curve (AUC) of 0.73 for the screening cohort and 0.72 for the validation cohort. The predictive logistic model constructed using a combination of WGRS and AF clinical risk factors (age, body mass index, sex, and hypertension) demonstrated better discrimination of AF than WGRS alone (AUC = 0.84; sensitivity 75.4%; specificity 80.2%). CONCLUSION: This novel predictive model of combined AF-associated SNPs and known clinical risk factors can accurately stratify AF risk in the Japanese population.

HotBalloon ablation of atrial fibrillation in patients with dextrocardia and situs inversus by "mirror image" approach.

A 51-year-old man with dextrocardia and complete situs inversus who presented with palpitation as a result of drug refractory paroxysmal atrial fibrillation (AF) was referred to our hospital for catheter ablation. Pulmonary vein isolation (PVI) was performed using the HotBalloon technique. We were able to accomplish AF ablation safely and easily using 180 degree-inversed mirror images of X-ray fluoroscopy. We have reported successful PVI for AF with dextrocardia using HotBalloon and mirror image of X-ray fluoroscopy without any complication for the first time.

Residual anticoagulation activity in atrial fibrillation patients with temporary interrupted direct oral anticoagulants: Comparisons across 4 drugs.

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 24 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 (N = 32, mean ±â€¯SD, -67.7 ±â€¯14.8% [231.6 ±â€¯93.1 to 71.9 ±â€¯31.8 ng/mL]) was smaller than that for rivaroxaban (N = 28, -83.6 ±â€¯10.9% [234.2 ±â€¯96.6 to 34.3 ±â€¯19.8 ng/mL]; P < 0.001) and dabigatran (N = 20, -90.7 ±â€¯7.3% [135.3 ±â€¯68.3 to 12.6 ±â€¯10.6 ng/mL]; P < 0.001), with its greatest value measured 24 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%; P < 0.001) and edoxaban (N = 22, -81.9 ±â€¯15.2%; P = 0.049), and its remaining activity 24 h after the last dose was the highest in the apixaban group. A serum DOAC concentration measured 24 h after the last dose of >30 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; P = 0.01) and apixaban versus dabigatran (odds ratio 74.0; P < 0.001). CONCLUSION: The pattern of drug elimination from blood may vary depending on DOACs, and their residual activity may not be negligible even 24 h after the last intake.

Cardiac electrophysiological characteristics of silent paroxysmal atrial fibrillation: What causes asymptomaticity?

BACKGROUND: A diagnosis of silent paroxysmal atrial fibrillation (AF) is highly challenging due to its asymptomatic and intermittent nature. The goal of the present study was to clarify its asymptomaticity with the use of a comprehensive electrophysiological approach. METHODS: We prospectively compared (a) 24-hour Holter monitoring data, (b) invasive cardiac electrophysiological properties, (c) AF inducibility, and (d) outcome of radiofrequency catheter ablation between patients with symptomatic paroxysmal AF and those with silent paroxysmal AF, defined as transient asymptomatic AF detected by chance. RESULTS: Patients with silent paroxysmal AF (N = 57) were more likely than patients with symptomatic paroxysmal AF (N = 282) to be male (75.4% vs 56.7%; P = .009), and to have a previous stroke (17.5% vs 6.7%; P = .008), more prolonged atrio-His interval (114.9 ± 29.1 vs 105.5 ± 24.1 ms; P = .01), longer atrioventricular nodal effective refractory period (352.3 ± 103 vs 318.2 ± 77.2 ms; P = .007), slower Wenckebach cycle length (488.5 ± 83.9 vs 443.3 ± 74.9 ms; P < .001), and lower maximum heart rate during AF (128.7 ± 31.9 vs 143.9 ± 29.6 beats/min; P = .02). Atrial ectopy (median [interquartile range], 385 [88, 2430] vs 207 [73.8, 870.8] beats/24 h; P = .02) and pharmacological AF induction (66.7% vs 43.2%; P = .02) were more common in silent paroxysmal AF patients. There was no difference in the 1-year freedom from AF following the ablation between the two patient groups. CONCLUSIONS: The more attenuated atrioventricular conduction properties in silent paroxysmal AF patients may explain their asymptomatic nature, and their higher likelihood of atrial arrhythmias may increase the chance to detect AF episodes. Whether or not they benefit from catheter ablation is uncertain.

Ser96Ala genetic variant of the human histidine-rich calcium-binding protein is a genetic predictor of recurrence after catheter ablation in patients with paroxysmal atrial fibrillation.

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.

Chromosome 4q25 Variant rs6817105 Bring Sinus Node Dysfunction and Left Atrial Enlargement.

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.

Maintenance of low inflammation level by the ZFHX3 SNP rs2106261 minor allele contributes to reduced atrial fibrillation recurrence after pulmonary vein isolation.

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.

HCN4 Gene Polymorphisms Are Associated With Occurrence of Tachycardia-Induced Cardiomyopathy in Patients With Atrial Fibrillation.

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.

H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters.

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.

A Comparison between the Instantaneous Wave-free Ratio and Resting Distal Coronary Artery Pressure/Aortic Pressure and the Fractional Flow Reserve: The Diagnostic Accuracy Can Be Improved by the Use of both Indices.

Objectives The fractional flow reserve (FFR) is an index of the severity of coronary stenosis that has been clinically validated in several studies. The instantaneous wave-free ratio (iFR) and the resting distal coronary artery pressure/aortic pressure (Pd/Pa) are nonhyperemic pressure-derived indices of the severity of stenosis. This study sought to examine the diagnostic accuracy of the iFR and resting Pd/Pa with respect to hyperemic FFR. Methods Following an intracoronary injection of papaverine, the iFR, resting Pd/Pa, and FFR were continuously measured in 123 lesions in 103 patients with stable coronary disease. Results The iFR and resting Pd/Pa values were strongly correlated with the FFR (R=0.794, p<0.001, R=0.832, p<0.0001, respectively). A receiver operator curve (ROC) analysis revealed that the optimal iFR cut-off value for predicting an FFR of <0.80 was 0.89 (AUC 0.901, sensitivity 84.1%, specificity 80.0%, positive predictive value 69.8%, negative predictive value 90.0%, diagnostic accuracy 81.3%), while the optimal resting Pd/Pa cut-off value was 0.92 (AUC 0.925, sensitivity 90.9%, specificity 78.5%, positive predictive value 70.2%, negative predictive value 93.9%, diagnostic accuracy 82.9%). The lesions with an iFR value of ≤0.89 and a Pd/Pa value of ≤0.92 were defined as double-positive lesions, while the lesions with an iFR value of >0.89 and a Pd/Pa value of >0.92 were defined as double-negative lesions. In these 109 lesions, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 92.3%, 82.9%, 75.0%, 95.1%, and 86.2%, respectively. Conclusion This analysis demonstrated that the iFR and resting Pd/Pa were strongly correlated with the FFR and that the diagnostic accuracy of the iFR was similar to that of the resting Pd/Pa. The diagnostic accuracy can be improved with the use of both the iFR and the resting Pd/Pa.

Contrast-induced Hyperemia as an Alternative to Drug-induced Hyperemia in the Evaluation of the Fractional Flow Reserve in Coronary Lesions.

Objective Measuring the fractional flow reserve (FFR) requires the induction of coronary hyperemia, usually with adenosine, adenosine triphosphate (ATP), or papaverine. However, adenosine can induce rhythmic complications, and intracoronary boluses of papaverine that prolong the QT interval can cause ventricular tachycardia. Injection of contrast media, which is routinely performed to validate the FFR guidewire placement, also induces hyperemia and may be an alternative method of measuring the FFR. We evaluated the diagnostic accuracy of the FFR after contrast hyperemia (FFRcont) compared to FFR evaluated after intracoronary papaverine (FFRpp). Methods This study included 109 lesions in 93 patients (mean age 70.4±8.7 years) with stable coronary disease. The FFR was measured as follows: 1) baseline pressure value; 2) FFRcont after intracoronary contrast injection (iopamidol, 8 mL for left coronary artery [LCA] or 6 mL for right coronary artery [RCA]); 3) FFRpp after intracoronary injection of papaverine (12 mg for LCA or 8 mg for RCA). Results FFRcont values were strongly correlated with FFRpp (R=0.940, p<0.0001; FFRpp = FFRcont ×1.007-0.032). The best cut-off point in the receiver operator curve analysis for predicting a FFRpp <0.80 was 0.82 (area under the curve =0.980; sensitivity 95.1%, specificity 91.2%, positive predictive value 86.7%, negative predictive value 96.9%). Conclusion FFRcont is highly accurate for predicting FFRpp. An FFRcont threshold value of 0.82 provides excellent sensitivity and a negative predictive value. FFRcont is an alternative method of inducing hyperemia.

The Difference between the optical coherence tomography (OCT) findings of newly progressed coronary lesions in symptomatic and asymptomatic patients.

BACKGROUND: Generally, newly progressed coronary lesions (NPCLs) are considered to be composed of lipid-rich plaques. In case of vulnerable plaque rupture, they may quickly become culprit lesions responsible for acute coronary syndromes. METHODS: Between September 2011 and September 2015, 2034 patients underwent scheduled follow-up coronary angiography (CAG) after percutaneous coronary intervention (PCI) in Tsuchiya General Hospital. Patients with NPCLs found by CAG during the follow-up period were evaluated by optical coherence tomography (OCT). NPCLs were defined as the lesions with less than 50% diameter stenosis, which progressed to more than 75% diameter stenosis within 3years after the previous CAG. Patients with restenosis after PCI were excluded. We compared OCT findings of NPCLs between symptomatic and asymptomatic patients. RESULTS: The follow-up CAG showed NPCLs in 64 patients (3.2%). OCT revealed fibrous plaque in 42 patients (65.6%) and thin-cap fibroatheroma in one patient. Thirteen patients had chest symptoms for one month before CAG and the remaining 51 patients were asymptomatic. The prevalence of fibrous plaque and intimal disruption or plaque rupture were not significantly different between symptomatic and asymptomatic patients (61.5% vs. 66.7%, p=0.752 and 30.8% vs. 11.8%, p=0.213, respectively). However, thrombi were more frequently observed in symptomatic patients (61.5% vs. 13.7%, p<0.001). CONCLUSIONS: The majority of NPCLs found in asymptomatic patients at follow-up CAG were not vulnerable; however, those found in symptomatic patients might be vulnerable. In clinical practice, NPCLs found in asymptomatic patients should be evaluated for functional severity of stenosis in order to determine the need for coronary revascularization.

Comparison of everolimus- and paclitaxel-eluting stents in dialysis patients.

BACKGROUND: We previously reported that the incidence of 1-year major adverse cardiac events (MACE) in patients treated with paclitaxel-eluting stents (PES) was lower than that in the sirolimus-eluting stents in dialysis patients. However, it remains unclear whether there are differences in clinical outcomes between everolimus-eluting stents (EES) and PES. METHODS: Between February 2010 and September 2013, 102 maintenance dialysis patients with 135 lesions treated with EES were compared to 107 maintenance dialysis patients with 147 lesions treated with PES. One-year clinical outcomes were investigated. RESULTS: Diabetes mellitus was present in 64.7% in the EES group and 71.0% in the PES group (p = 0.33). Heavy calcification was in 27.4% vs. 34.0% (p = 0.23). Rotational atherectomy was undergone in 11.1% vs. 23.1% (p < 0.01). Total stented length was not significantly different (23.5 ± 14.6 mm vs. 24.4 ± 13.2 mm, p = 0.60). One patient in the EES group was lost to follow up. At 12 months, MACE occurred in 13.2% in the EES group and 17.4% in the PES group (p = 0.25). Target lesion revascularization (TLR) was observed in 9.5% vs. 10.4% respectively (p = 0.77). Mortality was 11.8% vs. 13.1% (p = 0.35). Cardiac death was 5.0% vs. 7.7% (p = 0.09). Definite stent thrombosis was observed in 2.0% vs. 0% (p = 0.14). Subgroup analysis in patients with diabetes mellitus revealed no significant differences in MACE (12.7% vs. 14.9%, p = 0.36), TLR (8.3% vs. 7.4%, p = 0.42), mortality (13.7% vs. 13.2%, p = 0.28), and cardiac death (6.3% vs. 8.0%, p = 0.15) between the two groups. CONCLUSIONS: One-year clinical outcomes following EES and PES implantations are similar in dialysis patients.

Smoking cessation reverses DNA double-strand breaks in human mononuclear cells.

OBJECTIVE: Cigarette smoking is a major risk factor for atherosclerotic cardiovascular disease, which is responsible for a significant proportion of smoking-related deaths. However, the precise mechanism whereby smoking induces this pathology has not been fully delineated. Based on observation of DNA double-strand breaks (DSBs), the most harmful type of DNA damage, in atherosclerotic lesions, we hypothesized that there is a direct association between smoking and DSBs. The goal of this study was to investigate whether smoking induces DSBs and smoking cessation reverses DSBs in vivo through examination of peripheral mononuclear cells (MNCs). APPROACH AND RESULTS: Immunoreactivity of oxidative modification of DNA and DSBs were increased in human atherosclerotic lesions but not in the adjacent normal area. DSBs in human MNCs isolated from the blood of volunteers can be detected as cytologically visible "foci" using an antibody against the phosphorylated form of the histone H2AX (γ-H2AX). Young healthy active smokers (n = 15) showed increased γ-H2AX foci number when compared with non-smokers (n = 12) (foci number/cell: median, 0.37/cell; interquartile range [IQR], 0.31-0.58 vs. 4.36/cell; IQR, 3.09-7.39, p<0.0001). Smoking cessation for 1 month reduced the γ-H2AX foci number (median, 4.44/cell; IQR, 4.36-5.24 to 0.28/cell; IQR, 0.12-0.53, p<0.05). A positive correlation was noted between γ-H2AX foci number and exhaled carbon monoxide levels (r = 0.75, p<0.01). CONCLUSIONS: Smoking induces DSBs in human MNCs in vivo, and importantly, smoking cessation for 1 month resulted in a decrease in DSBs to a level comparable to that seen in non-smokers. These data reinforce the notion that the cigarette smoking induces DSBs and highlight the importance of smoking cessation.