Prolonged PR intervals are associated with epicardial adipose tissue and recurrence after catheter ablation in persistent atrial fibrillation.

Epicardial adipose tissue (EAT) has been reported to promote myocardial fibrosis and to affect intracardiac conduction. The PR interval reflects the conduction from the atria to the Purkinje fibers and may be associated with the EAT volume, especially in persistent atrial fibrillation (AF) patients. We aimed to investigate the relationship between the EAT and PR interval in patients with persistent AF. We enrolled 268 persistent AF patients who underwent catheter ablation (CA) and divided the patients into two groups: the normal PR interval group (PR interval less than 200 ms: Group N) and long PR interval group (PR interval 200 ms or more: Group L). We then analyzed the association between the total EAT volume around the heart and PR interval and calculated the ratio of the duration of the P wave (PWD) to the PR interval (PWD/PR interval). Moreover, we investigated whether a long PR interval was associated with the outcomes after ablation. The total EAT volume was significantly larger in Group L than Group N (Group N: 131.4 ± 51.8 ml vs. Group L: 151.3 ± 63.3 ml, p = 0.039). A positive correlation was also observed between the PWD/PR interval and EAT volume in Group L (r = 0.345, p = 0.039). A multivariate analysis also revealed that a long PR interval was independently associated with AF recurrence after CA (hazard ratio [HR] 2.071, p = 0.032). The total EAT volume was associated with a long PR interval, and a long PR interval was a significant risk factor for recurrence after ablation in persistent AF patients.

Impact of Lipoprotein (a) on Long-Term Outcomes in Patients With Acute Myocardial Infarction.

BACKGROUND: Lipoprotein (a) (Lp(a)) is a complex circulating lipoprotein, and there is increasing evidence it is a risk factor for atherosclerotic cardiovascular disease (ASCVD). This study aimed to investigate the influence of Lp(a) serum levels on long-term outcomes after acute myocardial infarction (AMI).Methods and Results: Between January 2015 and January 2018, we enrolled 262 patients with AMI who underwent coronary angiography within 24 h of the onset of chest pain and had available Lp(a) data enabling subdivision into 2 groups: high Lp(a) (≥32 mg/dL: n=76) and low Lp(a) (<32 mg/dL: n=186). The primary endpoint was major adverse cardiac events (MACE), which was defined as a composite of cardiac death, nonfatal MI, and readmission for heart failure. Multivariate Cox regression analysis was performed to identify the predictors of MACE. The incidence of MACE was significantly higher in the high Lp(a) group than in the low Lp(a) group (32.8% vs. 19.6%, P=0.004). Multivariate analysis showed that Lp(a) ≥32 mg/dL was an independent predictor of MACE (hazard ratio 2.84, 95% confidence interval 1.25-6.60, P=0.013). CONCLUSIONS: High Lp(a) levels were associated with worse long-term outcomes after AMI, so Lp(a) may be useful for risk assessment.

Increased major bleeding incidence in atrial fibrillation patients with apixaban: a review of Japanese post-marketing surveillance studies of direct oral anticoagulants.

Large-scaled post-marketing surveillance studies (PMSSs) of 4 direct oral anticoagulants (DOACs) for stroke prevention in non-valvular atrial fibrillation (AF) were conducted since 2011 in Japan, and the results of the last one have recently been published. Each reported a more than acceptable ischemic stroke prevention. The major bleeding rates were also acceptably low and comparable to each other in the PMSSs of dabigatran (J-dabigatran), rivaroxaban (XAPASS), and edoxaban (ETNA-AF-Japan). However, the incidence in PMSS of apixaban (STANDARD) was more than double the others. This finding appeared to contradict the globally accepted theory that apixaban is less likely than other DOACs to cause bleeding events. Possible responsible mechanisms included (1) the age and kidney function, (2) concomitant antiplatelet therapy, (3) drug actions, (4) follow-up duration, and (5) dose reduction criteria. Similarities in the clinical background shared by the 4 different PMSSs' participants and knowledge from previous studies did not support a dominant contribution of any of those former 4 factors to the increased major bleeding incidence in STANDARD. A possibility of the 5th factor was then examined. An estimated calculation we created showed that apixaban's dose reduction criteria was strict enough to considerably reduce the opportunity for participants to take its reduced rather than standard dose. We then successfully simulated how the "strict" dose reduction criteria would have increased the bleeding event rates under DOAC therapy. The discussion in this review may therefore raise a question about the validity of the current dose reduction criteria of apixaban for Japanese AF patients.

Progression from paroxysmal to persistent atrial fibrillation in pacemaker patients with tachycardia-bradycardia syndrome: a multicenter study.

Progression from paroxysmal to persistent atrial fibrillation (AF) is occasionally encountered in patients with previous pacemaker implantation (PMI) for the treatment of tachycardia-bradycardia syndrome (TBS). We aimed to determine the rate of its incidence occurring within the early years after PMI and the predictors. We studied TBS patients who received PMI at 5 core cardiovascular centers. The end point was a conversion from paroxysmal to persistent AF. We extracted 342 TBS patients out of 2579 undergoing PMI. During 5 ± 3.1 years of follow-up, 114 (33.3%) reached the end point. The time to the end point was 2.9 ± 2.7 years. The event rates within a year and 3 years after the PMI were 8.8% and 19.6%, respectively. In the multivariate hazard analyses, hypertension (hazard ratio [HR] 3.2, P = 0.03) and congestive heart failure (HR 2.1, P = 0.04) were found to be independent predictors of the end point occurring within a year after the PMI. Congestive heart failure (HR 1.82, P = 0.04), left atrial diameter of ≥ 40 mm (HR 4.55, P < 0.001), and the use of antiarrhythmic agents (HR 0.58, P = 0.04) were independently associated with the 3-year end point. Prediction models including combinations of those 4 parameters for the 1- and 3-year incidence both exhibited a modest risk discrimination (both c-statistics 0.71). In conclusion, early progression from paroxysmal to persistent AF was less frequent than expected in the TBS patients with PMI. Factors related to atrial remodeling and no use of antiarrhythmic drugs may facilitate the progression.

Peripheral arterial tone during active standing.

Active standing test is clinically used to detect inadequate sympathetic nervous system response to the orthostasis. Peripheral arterial tone (PAT) is a recently developed technology whereby sympathetic activity can be measured through monitoring the digit arterial pulsatile volume. We aimed to determine the response of PAT to the orthostasis. The PAT and short-time frequency domain heart rate variability (HRV) were simultaneously measured during a 5.5-min active standing test in volunteers. The endpoints were changes in the PAT and ratio of low frequency to high frequency (LH/HF) before and after the postural changes: sitting→standing→sitting again. The blood pressure (BP) was constant throughout the test while the heart rate increased during standing in 54 participants. The natural logarithm of the mean LF/HF increased in the standing position (sitting, standing, and sitting again, mean±standard deviation, 1.3±1.04, 1.73±1.15, and 1.51±0.94; p=0.006), and the natural logarithm of its peak value was the highest also while standing (2.58±1.19, 3.08±1.2, and 2.85±1.05; p=0.007). The mean PAT (487.5±277.7, 314.5±180.4, and 458.1±244.3; p <0.001) and its nadir value (341.8±204.8, 189.4±119.2, and 264.3±157.6; p <0.001) declined during standing, and reascended after sitting again. The percent change before and after the standing in mean PAT was not correlated with that of the mean LF/HF. In conclusion, the PAT changed independently of and inversely with the LF/HF during the orthostatic test while the BP remained constant, possibly reflecting peripheral vasocontraction needed for the BP homeostasis.

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.

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.

Differences in prothrombotic response between the uninterrupted and interrupted apixaban therapies in patients undergoing cryoballoon ablation for paroxysmal atrial fibrillation: a randomized controlled study.

Periprocedural bleeding and thromboembolic events are worrisome complications of catheter ablation for atrial fibrillation (AF). Periprocedural anticoagulation management could decrease the risk of these complications. However, evaluation of the complications from pulmonary vein isolation using cryoballoon related to different anticoagulation strategies is limited. Therefore, we aimed to compare prothrombotic responses as assessed on the basis of D-dimer levels between the uninterrupted and interrupted apixaban therapies during cryoballoon ablation. Ninety-seven consecutive patients with paroxysmal AF scheduled to undergo cryoballoon ablation were randomly assigned in a 1:2 ratio to uninterrupted apixaban therapy (Group 1, n = 32) or interrupted apixaban therapy (Group 2, n = 65). D-Dimer levels were measured immediately before the ablation, at the end of the ablation, and 24 and 48 h after the procedure. No statistical difference was observed in the baseline characteristics between the two groups. The rates of hemorrhagic complications were similar in both groups (major bleeding: 3.1 vs. 1.5%; p = 0.61, and minor bleeding: 3.1 vs. 4.6%; p = 0.73, respectively). No thromboembolic events occurred in either group. However, D-dimer levels 48 h after the ablation increased more markedly following the procedure in Group 2 than in Group 1 (from 0.58 ± 0.16 to 1.01 ± 0.42 µg/mL vs. 0.58 ± 0.20 to 0.82 ± 0.25 µg/mL; p = 0.01). In conclusion, uninterrupted apixaban therapy during the periprocedural period of cryoballoon ablation for AF did not increase the risk of bleeding in this study and might reduce the periprocedural risk of subclinical hypercoagulable state.

Correction to: Differences in prothrombotic response between the uninterrupted and interrupted apixaban therapies in patients undergoing cryoballoon ablation for paroxysmal atrial fibrillation: a randomized controlled study.

In the original publication of the article, the table 2 was published incorrectly.

Increased Urinary Liver-Type Fatty Acid-Binding Protein Level Predicts Worsening Renal Function in Patients With Acute Heart Failure.

BACKGROUND: Urinary liver-type fatty acid-binding protein (L-FABP) is a potential biomarker for acute kidney injury, and it in turn increases cardiovascular mortality. We tested whether the urinary L-FABP level predicted short- and mid-term outcomes in patients with acute heart failure. METHODS AND RESULTS: We enrolled consecutive patients with acute heart failure, and measured their urinary L-FABP levels before acute treatment. Worsening renal function (WRF), defined as both an absolute increase in the serum creatinine level of ≥0.3mg/dL and a ≥25% relative increase in its level from baseline, occurred in 37 (26.8%) of 138 patients. Patients with a urinary L-FABP level above the upper normal limit (8.4 µg/g creatinine) (n = 49; 35.5%) were more likely than those with a urinary L-FABP level within normal limits (n = 89; 64.5%) to develop WRF (n = 26 [53.1%] vs n = 11 [12.4%]; P < .001). A urinary L-FABP level above the upper limit was independently associated with WRF (hazard ratio 1.8; P = .01). During 1 year of follow-up, 12 patients (8.7%) died, and urinary L-FABP level had no association with all-cause mortality. There was, however, a tendency toward a higher readmission rate in patients with a urinary L-FABP level above the upper normal limit who survived the index hospitalization (n = 46) than in those without an abnormal L-FABP level (n = 88; n = 13 [28.3%] vs n = 13 [14.8%]; log-rank P = .06). CONCLUSIONS: Increased urinary L-FABP level before treatment may predict WRF in patients with acute heart failure. Further investigation is warranted for its predictive ability of adverse outcomes.

Real-life experience of a stent-less revascularization strategy using a combination of excimer laser and drug-coated balloon for patients with acute coronary syndrome.

OBJECTIVES: We aimed to test a novel stent-less revascularization strategy using a combination of excimer laser coronary angioplasty (ELCA) and drug-coated balloon (DCB) for patients with acute coronary syndrome (ACS). BACKGROUND: Percutaneous coronary intervention with drug eluting stents is a standard invasive treatment for ACS. Some unsolved issues however remain, such as stent thrombosis and bleeding risks associated with dual antiplatelet therapy. METHODS: Consecutive ACS patients were planned to receive either a DCB application following ELCA without a stent implantation or conventional revascularization with a coronary stent. The endpoints were (i) major cardiac adverse events (MACEs), defined as the composite of cardiac death, myocardial infarctions, and target lesion revascularization; (ii) target vessel revascularization (TVR); and (iii) angiographic outcome. RESULTS: Since a greater than expected number of patients allocated to the stent-less treatment arm eventually received a bailout stenting, the following 3 as-treated groups were compared; DCB with ELCA group (N = 60), Stent with ELCA group (N = 23), and Stent without ELCA group (N = 85). During a mean follow-up period of 420 ± 137 days, and with angiographic 6- and 12-month-follow-up rates of 96.7%, 87%, and 81.2%, and 50%, 65.2%, and 45.9%, respectively, the MACE rate did not differ across the groups (10%, 4.3%, and 3.5%; P = 0.22) while an incidence of TVR was more common (15%, 0, and 4.7%; P = 0.02) and the diameter stenosis at 6-months of follow-up was greater (25.7 ± 18.2, 14.9 ± 13.1 and 16.2 ± 15.4%; P = 0.002) in the DCB with ELCA group. CONCLUSIONS: The stent-less revascularization strategy with DCB and ELCA was associated with a higher occurrence of restenosis in ACS patients.

Head-to-head comparison of acute and chronic pulmonary vein stenosis for cryoballoon versus radiofrequency ablation.

BACKGROUND: Cryoballoon (CB) applications to pulmonary veins (PVs) can cause stenosis just as radiofrequency (RF) energy deliveries. The goal of the present study was to clarify whether or not there was any difference in the extent of acute or chronic PV narrowing after PV isolation between the two different energy sources. METHODS: Consecutive patients with paroxysmal atrial fibrillation who were scheduled to undergo a PV isolation were randomized 1:1 to receive CB or RF ablation. The endpoints were any acute PV narrowing assessed with the use of intracardiac ultrasound during the procedure and PV stenosis measured with cardiac computed tomography at the 3-month follow-up. RESULTS: An acute reduction in the luminal area of the left superior PV (mean ± standard deviation, -6.8 ± 8.7 vs -19.9 ± 14.7%; P < 0.001) and left inferior PV (-5.1 ± 20.2 vs -15.3 ± 11.6%; P = 0.03) was significantly smaller in the CB arm (N = 25) than the RF arm (N = 25). There was no difference in the extent of PV stenosis 3 months after the ablation between the arms (0-25% stenosis, 90% vs 88%, 25-50% stenosis, 10% vs 12%, >50% stenosis, both 0%; P = 0.82). A greater acute PV narrowing was likely to lead to chronic stenosis in the RF arm (P = 0.004). CONCLUSIONS: CB ablation may reduce the acute narrowing of the left-sided PVs as compared to RF ablation.

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.

Cardiac resynchronization therapy for patients with cardiac sarcoidosis.

Aims: Sarcoidosis with cardiac involvement is a rare pathological condition, and therefore cardiac resynchronization therapy (CRT) for patients with cardiac sarcoidosis is even further rare. We aimed to clarify the clinical features of patients with cardiac sarcoidosis who received CRT. Methods and results: We retrospectively reviewed the clinical data on CRT at three cardiovascular centres to detect cardiac sarcoidosis patients. We identified 18 (8.9%) patients with cardiac sarcoidosis who met the inclusion criteria out of 202 with systolic heart failure who received CRT based on the guidelines. The majority of the patients were female [15 (83.3%)] and underwent an upgrade from a pacemaker or implantable cardioverter defibrillator [13 (72.2%)]. We found 1 (5.6%) cardiovascular death during the follow-up period (mean ± SD, 4.7 ± 3.0 years). Seven (38.9%) patients had a composite outcome of cardiovascular death or hospitalization from worsening heart failure within 5 years after the CRT. Twelve (66.7%) patients had a history of sustained ventricular arrhythmias or those occurring after the CRT. Among the overall patients, no significant improvement was found in either the end-systolic volume or left ventricular ejection fraction (LVEF) 6 months after the CRT. A worsening LVEF was, however, more likely to be seen in 5 (27.8%) patients with ventricular arrhythmias after the CRT than in those without (P = 0.04). An improved clinical composite score was seen in 10 (55.6%) patients. Conclusions: Cardiac sarcoidosis patients receiving CRT may have poor LV reverse remodelling and a high incidence of ventricular arrhythmias.

Electrical Remodeling of the Atrioventricular Node Caused by Persistent Atrial Fibrillation in Humans.

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.

Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese.

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.

Dexmedetomidine Depresses Sinoatrial and Atrioventricular Nodal Function Without Any Change in Atrial Fibrillation Inducibility.

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.

Who is the operator, that is the question: a multicentre study of catheter ablation of atrial fibrillation.

AIMS: A worldwide survey reported that the success rate of atrial fibrillation (AF) ablation was higher in high-volume centers compared with low-volume centers. We tested whether the procedure volume of each operator was associated with the outcome of AF ablation in high-volume centres. METHODS AND RESULTS: We studied 471 patients with paroxysmal AF who underwent pulmonary vein (PV) isolation for the first time in three cardiovascular centers where the annual AF ablation volume was >100 procedures. We classified a total of 10 primary operators according to their operation volume on the basis of ACC/AHA/ACP CLINICAL COMPETENCE STATEMENT; high-volume operator (≥50 cases/year, N = 3) or low-volume operator (<50 cases/year, N = 7). The patients included were dichotomized according to the annual operation volume of their attending physician. The endpoints were the freedom from AF recurrence 1 year after the ablation, major complications including thromboembolisms, massive bleeding or death, and the procedural duration. RESULTS: A complete isolation of the four PVs was achieved in 99.1%. The freedom from AF recurrence was more common in patients treated by high-volume operators than those treated by low-volume operators (165/216 [76.4%] vs. 160/255 [62.8%]; P = 0.001). A high-volume operator was the only independent predictor of the freedom from AF recurrence (hazard ratio 1.73, 95% confidence interval 1.23-2.48; P = 0.002). The patients treated by high-volume operators were less likely to have major complications (1.4% vs. 7.8%; P = 0.001), and had a shorter procedural duration (139.9 ± 25.3 vs. 149.3 ± 27.1 min; P = 0.03). CONCLUSIONS: Operator proficiency may predict the outcome after AF ablation even in high-volume centres.

A nonsynonymous polymorphism in semaphorin 3A as a risk factor for human unexplained cardiac arrest with documented ventricular fibrillation.

Unexplained cardiac arrest (UCA) with documented ventricular fibrillation (VF) is a major cause of sudden cardiac death. Abnormal sympathetic innervations have been shown to be a trigger of ventricular fibrillation. Further, adequate expression of SEMA3A was reported to be critical for normal patterning of cardiac sympathetic innervation. We investigated the relevance of the semaphorin 3A (SEMA3A) gene located at chromosome 5 in the etiology of UCA. Eighty-three Japanese patients diagnosed with UCA and 2,958 healthy controls from two different geographic regions in Japan were enrolled. A nonsynonymous polymorphism (I334V, rs138694505A>G) in exon 10 of the SEMA3A gene identified through resequencing was significantly associated with UCA (combined P = 0.0004, OR 3.08, 95%CI 1.67-5.7). Overall, 15.7% of UCA patients carried the risk genotype G, whereas only 5.6% did in controls. In patients with SEMA3A(I334V), VF predominantly occurred at rest during the night. They showed sinus bradycardia, and their RR intervals on the 12-lead electrocardiography tended to be longer than those in patients without SEMA3A(I334V) (1031±111 ms versus 932±182 ms, P = 0.039). Immunofluorescence staining of cardiac biopsy specimens revealed that sympathetic nerves, which are absent in the subendocardial layer in normal hearts, extended to the subendocardial layer only in patients with SEMA3A(I334V). Functional analyses revealed that the axon-repelling and axon-collapsing activities of mutant SEMA3A(I334V) genes were significantly weaker than those of wild-type SEMA3A genes. A high incidence of SEMA3A(I334V) in UCA patients and inappropriate innervation patterning in their hearts implicate involvement of the SEMA3A gene in the pathogenesis of UCA.

Incomplete cure of tachycardia-induced cardiomyopathy secondary to rapid atrial fibrillation by heart rate control without sinus conversion.

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.