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.

Coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone improves postprandial endothelial dysfunction in patients with borderline and stage 1 hypertension.

PURPOSE: The purpose of this study was to evaluate acute effects of coffee with a high content of chlorogenic acids and different hydroxyhydroquinone contents on postprandial endothelial dysfunction. METHODS: This was a single-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 37 patients with borderline or stage 1 hypertension were randomized to two study groups. The participants consumed a test meal with a single intake of the test coffee. Subjects in the Study 1 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or placebo coffee with crossover. Endothelial function assessed by flow-mediated vasodilation and plasma concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after coffee intake. RESULTS: Compared with baseline values, single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone, but not coffee with a high content of chlorogenic acids and high content of hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow-mediated vasodilation and decreased circulating 8-isoprostane levels. CONCLUSIONS: These findings suggest that a single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone is effective for improving postprandial endothelial dysfunction. CLINICAL TRIAL REGISTRATION: URL for Clinical Trial: https://upload.umin.ac.jp ; Registration Number for Clinical Trial: UMIN000013283.

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.

Mechanical and substrate abnormalities of the left atrium assessed by 3-dimensional speckle-tracking echocardiography and electroanatomic mapping system in patients with paroxysmal atrial fibrillation.

BACKGROUND: Left atrial (LA) remodeling progresses to electrical remodeling, contractile remodeling, and subsequently structural remodeling. Little is known about the relationship between LA electrical and anatomical remodeling and LA mechanical function. OBJECTIVES: We aimed to clarify the relationship between LA mechanical function using 3-dimensional speckle-tracking echocardiography (3D-STE) and LA electrical remodeling using an electroanatomic mapping system (CARTO 3) and to estimate atrial fibrillation (AF) substrate in patients with paroxysmal AF (PAF). METHODS: A total of 52 patients with PAF (41 (79%) men; mean age 61 ± 11 years) undergoing their initial pulmonary vein isolation (PVI) were examined. The standard deviation of the time to peak strain in each LA segment (%SD-TPS) was analyzed as an index of LA dyssynchrony using 3D-STE before PVI. Contact LA bipolar voltage and activation maps were constructed during sinus rhythm before PVI using CARTO 3. The LA total activation time was measured and low-voltage zones (LVZs) were determined with a local bipolar electrogram amplitude of <0.5 mV. The patients were divided into those with an LVZ (LVZ group; n = 23) and those without an LVZ (non-LVZ group; n = 29). RESULTS: The %SD-TPS was significantly higher (14.1 ± 5.7 vs 8.0 ± 5.1; P=.0002) in the LVZ group than in the non-LVZ group and was an independent determinant of the LVZ (odds ratio 1.21; 95% confidence interval 1.04-1.49; P=.01). In addition, the LA total activation time was weakly correlated with the %SD-TPS. CONCLUSION: LA dyssynchrony and conduction delay exist in patients with PAF. The 3D-STE enabled noninvasive estimation of LA electrical remodeling and AF substrate.

Effects of ezetimibe on serum polyunsaturated fatty acids in patients with coronary artery disease.

Residual risk of cardiovascular disease might stem, at least partially, from low serum concentrations of n-3 polyunsaturated fatty acid (PUFA). The purpose of this study was to evaluate the effects of ezetimibe on serum lipids and PU-FAs in patients with coronary artery disease who were intolerant of new or high-dose statin therapy. The study population consisted of 13 patients who were intolerant of new statin therapy and 10 patients who were intolerant of high-dose statin therapy for the treatment of low-density lipoprotein (LDL) cholesterol. Patients who were intolerant of high-dose statin therapy continued taking a statin, but at a lower dose during the study period. Blood samples were collected before and 12 weeks after ezetimibe (10 mg). We measured serum lipids and PUFAs including dihomo-γ-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid. Ezetimibe significantly decreased LDL cholesterol (138 ± 19 mg/dL to 97 ± 34 mg/dL, P < 0.01), but did not significantly affect high-density lipoprotein cholesterol, triglyceride, or any of the PUFAs measured during the follow-up period. Consequently, it did not affect the ratio of EPA to AA (0.40 ± 0.17 to 0.43 ± 0.18, P = ns) or the ratio of n-3 PUFA to n-6 PUFA (1.10 ± 0.39 to 1.09 ± 0.36, P = ns) during the follow-up period. Ezetimibe in combination with a low-dose statin, or as monotherapy in statin-intolerant patients, decreased LDL cholesterol, but did not significantly affect serum PUFA concentrations in patients with coronary artery disease.

A head-to-head comparison of periprocedural coagulability under anticoagulation with rivaroxaban versus dabigatran in patients undergoing ablation of atrial fibrillation.

BACKGROUND AND OBJECTIVES: Two new oral anticoagulants, rivaroxaban and dabigatran, with no need for anticoagulation monitoring, are available for patients with atrial fibrillation (AF). We aimed to compare their anticoagulant effects and safety when used during the AF ablation periprocedural period. METHODS: Patients undergoing AF ablation were randomly assigned to receive rivaroxaban 15 mg once daily (N = 30) or dabigatran 110 mg twice daily (N = 30). Rivaroxaban was withheld on the morning of the day before the ablation, and dabigatran was discontinued from the evening of the day before the procedure. Both anticoagulants were then resumed after haemostasis of the access site. D-dimer levels were measured just before the ablation, at the end of the ablation, and at 24 h and 48 h after the procedure. RESULTS: The baseline D-dimer levels were identical in both groups. However, D-dimer levels increased more markedly following the ablation procedure in patients receiving rivaroxaban than in those receiving dabigatran (mean ± standard deviation from 0.62 ± 0.16 to 1.09 ± 0.38 µg/mL vs from 0.59 ± 0.08 to 0.75 ± 0.17 µg/mL; p < 0.0001). The rate of rebleeding from the access site was similar in patients receiving rivaroxaban and those receiving dabigatran (33 vs 27%; p = 0.78). CONCLUSION: As compared with dabigatran, rivaroxaban may increase the risk of hypercoagulability when used during the periprocedural period of AF ablation, suggesting a potential rebound effect of rivaroxaban or a mismatch between its half-life and dose regimen.

Variable procedural strategies adapted to anatomical characteristics in catheter ablation of the cavotricuspid isthmus using a preoperative multidetector computed tomography analysis.

OBJECTIVES: This study aimed to investigate the anatomical characteristics complicating cavotricuspid isthmus (CTI) ablation and the effectiveness of various procedural strategies. METHODS AND RESULTS: This study included 446 consecutive patients (362 males; mean age 60.5 ± 10.4 years) in whom CTI ablation was performed. A total of 80 consecutive patients were evaluated in a preliminary study. The anatomy of the CTI was evaluated by multidetector row-computed tomography (MDCT) prior to the procedure. A multivariate logistic regression analysis revealed that the angle and mean wall thickness of the CTI, a concave CTI morphology, and a prominent Eustachian ridge, were associated with a difficult CTI ablation (P < 0.01). In the main study, 366 consecutive patients were divided into 2 groups: a modulation group (catheter inversion technique for a concave aspect, prominent Eustachian ridge, and steep angle of the CTI or increased output for a thicker CTI) and nonmodulation group (conventional strategy). The duration and total amount of radiofrequency energy delivered were significantly shorter and smaller in the modulation group than those in the nonmodulation group (162.2 ± 153.5 vs 222.7 ± 191.9 seconds, P < 0.01, and 16,962.4 ± 11,545.6 vs 24,908.5 ± 22,804.2 J, P < 0.01, respectively). The recurrence rate of type 1 atrial flutter after the CTI ablation in the nonmodulation group was significantly higher than that in the modulation group (6.3 vs 1.7%, P = 0.02). CONCLUSION: Changing the procedural strategies by adaptating them to the anatomical characteristics improved the outcomes of the CTI ablation.

Association between serum levels of n-3 polyunsaturated fatty acids and coronary plaque detected by coronary computed tomography angiography in patients receiving statin therapy.

BACKGROUND: Intensive lipid-lowering therapy with statins reduces cardiovascular events, but residual cardiovascular risks remain. Intake of n-3 polyunsaturated fatty acids (PUFAs) has been associated with cardiovascular events. We examined the relationships between serum n-3 PUFAs and coronary atherosclerotic findings on computed tomography angiography (CTA) in patients undergoing statin treatment. METHODS AND RESULTS: We enrolled 172 subjects (mean age: 68.2 years; 64% men) prior to statin treatment for 6 months. Serum PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid, were measured. When the patients were divided into 2 groups according to the median EPA level (61.3 µg/ml), the low-EPA group showed higher incidences of 3-vessel plaque involvement (62% vs. 43%, P=0.015), noncalcified plaques (NCPs) (74% vs. 52%, P=0.0016), extensive NCPs (≥ 2 segments) (56% vs. 34%, P=0.0036), and high-risk plaques (minimum CT density <39 HU and remodeling index >1.05) (43% vs. 22%, P=0.0034). Multivariate analyses revealed that low EPA levels were an independent factor for these coronary plaque findings. The DHA levels were not independently associated with these findings. CONCLUSIONS: Low serum EPA level, but not serum DHA, is associated with the presence and extent of NCPs and high-risk plaques detected by coronary CTA in patients undergoing lipid-lowering therapy with statins.

Pulmonary artery mapping for differential diagnosis of left-sided atrial tachycardia.

BACKGROUND: Distinguishing left-and right-sided atrial tachycardia (AT) is often challenging. The coronary sinus (CS) provides information only concerning the anterior left atrium (LA). Potentials recorded in the pulmonary artery (PA) have been substituted for those of the upper posterior LA because of their anatomical relationship. METHODS AND RESULTS: Three patterns were designed, using potentials in the PA, right atrium (RA) and CS, to predict the side of AT. Two patterns were for left-sided AT and 1 pattern was for right-sided AT. Ten left-sided and 11 right-sided ATs were investigated regardless of mechanism. Electrode catheters were inserted in the RA, His bundle region, and CS, and an ablation catheter was inserted into the left and/or right PA. The sequences from these catheters were analyzed before detailed electroanatomical mapping. Patterns were obtained for 20 of 21 ATs. The mechanism was focal in 16 ATs and macroreentry in 5. The method predicted left-sided AT with a sensitivity of 78%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 84%, and an accuracy of 90%. CONCLUSIONS: The use of potentials in PA combined with conventional RA and CS electrograms is useful for distinguishing left-sided AT from right-sided AT, regardless of mechanism.

Novel assessment of temporal variation in fractionated electrograms using histogram analysis of local fractionation interval in patients with persistent atrial fibrillation.

BACKGROUND: The characteristics of atrial electrograms associated with atrial fibrillation (AF) termination are controversial. We investigated the electrogram characteristics that indicate procedural AF termination during continuous complex fractionated electrogram ablation. METHODS AND RESULTS: Fifty-two consecutive patients with persistent AF (47 men; aged 54 ± 9 years), who underwent electrogram-based catheter ablation in the left atrium and coronary sinus after pulmonary vein isolation, were enrolled. The intracardiac bipolar atrial electrogram recordings were characterized by (1) fractionation interval (FI) analysis (>6 seconds), (2) kurtosis (shape of the FI histogram), and (3) skewness (asymmetry of the FI histogram). Sites showing complex, fractionated electrograms (mean FI ≤ 60 ms) were targeted, and AF was terminated in 20 patients (38%) after the pulmonary vein isolation. The conventional complex fractionated electrogram sites (mean ≤ 120 ms) in patients with AF termination exhibited higher median kurtosis (2.69 [interquartile range, 2.03-3.46] versus 2.35 [interquartile range, 1.79-2.48]; P=0.024) and higher complex fractionated electrogram-mean interval (102.7 ± 19.8 versus 87.7 ± 15.0; P=0.008) than patients without AF termination. Furthermore, AF termination sites had higher median kurtosis than targeted sites without AF termination (5.13 [interquartile range, 3.51-6.47] versus 4.18 [interquartile range, 2.91-5.34]; P<0.01) in patients with procedural termination. In addition, patients with AF termination had a higher sinus rhythm maintenance rate after a single procedure than patients without AF termination (log-rank test, P=0.007). CONCLUSIONS: A kurtosis analysis using the FI histogram may be a useful tool in identifying the critical substrate for persistent AF and potential responders to catheter ablation.