Delineation of conduction gaps of linear lesions during atrial fibrillation ablation using ultra-high-density mapping.

AIMS: Linear lesions are routinely created by radiofrequency catheter ablation. Unwanted electrical conduction gaps can be produced and are often difficult to ablate. This study aimed to clarify the characteristics of conduction gaps during atrial fibrillation ablation by analysing bidirectional activation maps using a high-density mapping system (RHYTHMIA). METHODS AND RESULTS: This retrospective study included 31 patients who had conduction gaps along pulmonary vein (PV) isolation or box ablation lesions. Activation maps were sequentially created during pacing from the coronary sinus and PV to reveal the earliest activation site, defined by the entrance and exit. The locations, length between the entrance and exit (gap length), and direction were analysed. Thirty-four bidirectional activation maps were drawn: 21 were box isolation lesions (box group), and 13 were PV isolation lesions (PVI group). Among the box group, nine conduction gaps were present in the roof region and 12 in the bottom region, while nine in right PV and four in left PV among the PVI group. Gap lengths in the roof region were longer than those in the bottom region (26.8 ± 11.8 vs. 14.5 ± 9.8 mm; P = 0.022), while those in right PV tended to longer than those in left PV (28.0 ± 15.3 vs. 16.8 ± 8.0 mm, P = 0.201). CONCLUSION: The entrances and exits of electrical conduction gaps were separated, especially in the roof region, indicating that epicardial conduction might contribute to gap formation. Identifying the bidirectional conduction gap might indicate the location and direction of epicardial conduction.

Associations between plasma nesfatin-1 levels and the presence and severity of coronary artery disease.

Nesfatin-1 is a recently identified anorexigenic peptide mainly secreted from the brain and adipose tissue. Although nesfatin-1 may have pro-inflammatory and apoptotic properties, the association between plasma nesfatin-1 levels and coronary artery disease (CAD) has not been clarified yet. We investigated plasma nesfatin-1 levels in 302 patients undergoing elective coronary angiography. Of the 302 study patients, CAD was present in 172 (57%), of whom 67 had 1-vessel, 49 had 2-vessel, and 56 had 3-vessel disease. Compared with 130 patients without CAD, 172 with CAD had higher plasma nesfatin-1 levels (median 0.21 vs. 0.17 ng/mL, P < 0.01). A stepwise increase in nesfatin-1 levels was found depending on the number of > 50% stenotic coronary vessels: 0.17 in CAD(-), 0.20 in 1-vessel, 0.21 in 2-vessel, and 0.22 ng/mL in 3-vessel disease (P < 0.05). A high nesfatin-1 level (> 0.19 ng/mL) was found in 43% of patients with CAD(-), 55% of those with 1-vessel, 55% of those with 2-vessel, and 68% of those with 3-vessel disease (P < 0.05). Nesfatin-1 levels significantly correlated with the number of > 50% stenotic coronary segments (r = 0.14, P < 0.02). In multivariate analysis, plasma nesfatin-1 levels were a significant factor for CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.71 (95% CI 1.01-2.91) for high nesfatin-1 level of > 0.19 ng/mL (P < 0.05). Thus, plasma nesfatin-1 levels were found to be high in patients with CAD and were associated with CAD independent of atherosclerotic risk factors, suggesting that high nesfatin-1 levels in patients with CAD may play a role in the development of coronary atherosclerosis.

Assessment of patient characteristics influencing the complexity of leadless pacemaker implantation.

Background: The complexity of leadless pacemaker (LP) implantation varies widely. However, the predictive factors determining this difficulty are poorly understood. Objective: The purpose of this study was to evaluate the factors influencing LP implantation difficulty, specifically procedural time during right atrial (RA) and right ventricular (RV) manipulation, based on patient background, cardiac function, and anatomic characteristics. Methods: Analysis included LP implantation cases between 2017 and 2023, excluding the initial 3 implants performed by each operator. The relevance of patient background, cardiac function, and anatomic features on procedural and fluoroscopy times was evaluated. Results: Fifty-four patients (mean age 82.2 ± 10.0 years; 57.4% male) were included in the study. Median procedural and fluoroscopy time was 45.8 minutes and 16.0 minutes, respectively, with an average of 2.0 ± 1.4 device deployments. Univariate analysis showed associations between procedural time and older age, RA and RV diameter, and severity of tricuspid regurgitation (TR). After adjustment for physician and potential contributing factors, RV dilation (midventricular diameter ≥35 mm) and severe TR were identified as independent predictors of prolonged procedural time. Medical history exhibited no association with procedural time. Consistent results were observed in analyses using fluoroscopy time as the outcome. Conclusion: RV dilation and severe TR were associated with prolonged procedural time for LP implantation. Anatomic features obtained from preprocedural echocardiography could provide valuable insights into both the safety and efficiency of LP implantation, thereby enhancing tailored treatment strategies for patients undergoing pacemaker implantation.

Predictors and incidence of health status deterioration in patients with early atrial fibrillation.

BACKGROUND: Various treatment approaches for atrial fibrillation (AF) have demonstrated improved health status, yet the significance of these therapeutic interventions in individual patients remains unclear. OBJECTIVE: This study aimed to evaluate health status changes in patients with early AF, focusing on those who experience clinically significant deterioration after treatment initiation. METHODS: We analyzed data from a multicenter, prospective registry of newly diagnosed patients with AF. One-year changes in health status across different treatment strategies were assessed by the Atrial Fibrillation Effect on QualiTy-of-life Overall Summary (AFEQT-OS) score. Clinically relevant deterioration and improvement in health status were defined as ≥5-point decrease and increase in AFEQT-OS score, respectively; no change was -5 to 5 points. RESULTS: Overall, 1960 patients with AF were evaluated. Mean AFEQT-OS scores at baseline and 1-year follow-up were 76.7 ± 17.7 and 85.4 ± 14.8, respectively. Although most patients (53.9%) experienced clinically important improvement, a considerable proportion had no change (28.7%) or deterioration (17.4%) in their health status. Proportions of patients with no change or deterioration varied by treatment strategy: 59.9%, 53.9%, and 32.0% in rate control, antiarrhythmic drug, and catheter ablation groups, respectively. The multivariable model identified older age, female sex, heart failure, coronary artery disease, and higher baseline AFEQT-OS score as independent predictors of worsening health status, regardless of treatment strategy. CONCLUSION: Many patients with early AF experience worsening or no change in health status irrespective of treatment strategy. Standardizing patients' health status assessment, especially for patients with comorbidities, may aid in patients' selection and their outcomes.

Characteristics and health-status outcomes in patients with atrial fibrillation detected via health screening.

BACKGROUND: Early detection of atrial fibrillation (AF) is important. Japan has a universal screening system, and regular health screening (HS) is available to support AF detection without a hospital visit. However, health-related outcomes and other characteristics of HS-detected and conventionally diagnosed AF remain unknown. HYPOTHESIS: That the characteristics and health-related outcomes of patients with HS-detected AF may differ from those of patients whose AF was detected by other procedures. METHODS: In total, 3318 consecutive newly referred AF cases were enrolled; demographic characteristics and health-related and clinical outcomes were compared between two groups created based on the mode of AF detection (the HS and non-HS groups). Health-related outcomes were assessed using the AF Effect on QualiTy-of-life (AFEQT) questionnaire at baseline and after 1 year of follow-up. RESULTS: AF was detected by HS in 25.0% of patients; these patients had lower CHADS2 scores (1.01 vs. 1.50, p < .001), higher prevalence of persistent AF (odds ratio, 95% confidence interval; 2.21, 1.88-2.60) and asymptomatic presentation (3.19, 2.71-3.76), and better baseline QoL scores (83.6 vs. 75.0; p < .001). Catheter ablation was more frequently performed in the HS group at follow-up (44.4% vs. 34.1%; p < .001). At 1-year follow-up, the AFEQT scores of the HS group were significantly better in most subdomains. CONCLUSIONS: In the Japanese registry, AF was detected via HS in 25% of patients referred to specialty centers for management. Notably, the overall health status of patients with HS-detected AF improved after medical interventions, including catheter ablations.

Prognostic Implications and Efficacy of Catheter Ablation by Atrial Fibrillation Type.

Background Catheter ablation (CA) for atrial fibrillation (AF) is preferred for paroxysmal AF (PAF) but selectively performed in patients with persistent AF (PersAF). This study aimed to investigate the prognostic differences and consequences of CA based on the AF type. Methods and Results Data from a multicenter AF cohort study were analyzed, categorizing patients as PAF or PersAF according to AF duration (≤7 or >7 days, respectively). A composite of all-cause death, heart failure hospitalization, stroke, and bleeding events during 2-year follow-up and changes in the Atrial Fibrillation Effect on Quality-of-life score were compared. Additionally, propensity score matching was performed to compare clinical outcomes of patients with and without CA in both AF types. Among 2788 patients, 51.6% and 48.4% had PAF and PersAF, respectively. Patients with PersAF had a higher incidence of the composite outcome (12.8% versus 7.2%; P<0.001) and smaller improvements in Atrial Fibrillation Effect on Quality-of-life scores than those with PAF. After adjusting for baseline characteristics, PersAF was an independent predictor of adverse outcomes (adjusted hazard ratio, 1.35 [95% CI, 1.30-1.78], P=0.031) and was associated with poor improvements in Atrial Fibrillation Effect on Quality-of-life scores. Propensity score matching analysis showed that the CA group had significantly fewer adverse events than the medication group among patients with PAF (odds ratio, 0.31 [95% CI, 0.18-0.68]; P=0.002). Patients with PersAF showed a similar but nonsignificant trend. Conclusions PersAF is a risk factor for worse clinical outcomes, including patients' health status. CA is associated with fewer adverse events, although careful consideration is required based on the AF type.

Catheter ablation improves outcomes and quality of life in Japanese patients with early-stage atrial fibrillation: A retrospective cohort study.

BACKGROUND: Catheter ablation is widely used as first-line therapy for patients with impaired quality of life; however, whether catheter ablation improves survival and other outcomes in atrial fibrillation (AF) cases remains unclear. OBJECTIVE: The purpose of this study was to evaluate whether catheter ablation reduces adverse clinical outcomes and improves patients' quality of life using data from a contemporary Japanese multicenter registry of patients with early-stage AF. METHODS: The Keio Interhospital Cardiovascular Studies-Atrial Fibrillation registered 3318 patients with AF newly diagnosed at or referred to participating hospitals between 2014 and 2018. Propensity score matching based on 47 demographic variables was performed. We extracted 823 pairs who underwent catheter ablation or medical therapy alone. The primary outcome was the composite of all-cause death, stroke, bleeding events, and heart failure hospitalization during a 2-year follow-up period. Additionally, the Atrial Fibrillation Effect on QualiΤy-of-Life scores at baseline and 1-year follow-up were evaluated. RESULTS: Within the matched cohort, the median time since AF diagnosis was 0.3 years (interquartile range [IQR] 0.1‒2.3 years), age was 67.0 years (IQR 59.0‒73.0 years), and the CHA2DS2-VASc score was 2.0 (IQR 1.0‒2.0). During a median follow-up period of 730 days (IQR 366‒731 days), patients who underwent catheter ablation had a lower risk of primary outcomes (hazard ratio 0.49; 95% confidence interval 0.30‒0.79; P = .004), with a significantly lower risk of heart failure hospitalization (hazard ratio 0.33; 95% confidence interval 0.14-0.77; P = .010) and improved Atrial Fibrillation Effect on QualiΤy-of-Life scores, than did those who received medical therapy. CONCLUSION: In patients with propensity score-matched, early-stage, real-world AF, catheter ablation was associated with a lower risk of adverse clinical events and improved quality of life as compared with medical therapy.

Change in the local impedance and electrograms recorded by a micro-electrode tip catheter during initial atrial fibrillation ablation.

BACKGROUND: A novel measurement of the local impedance (LI) and electrograms recorded from micro-electrodes on catheter tip has been developed. However, the data during pulmonary vein (PV) ablation is not sufficient. We aimed to investigate the utility of this measurement during initial atrial fibrillation (AF) ablation. METHODS: We investigated 111 representative radiofrequency applications in 7 AF patients without a history of prior ablation (6 males, age 68 [65-72] years, 2 persistent AF). The ablation strategy was PV isolation for paroxysmal AF and single ring box isolation for persistent AF, using MiFi catheter. The correlation of the generator impedance (GI) drop and LI drop after radiofrequency applications and the predictive value of the initial LI elevation before radiofrequency applications for LI drop were analyzed. Also, the LI and GI drop were investigated according to the location of RF applications. RESULTS: The LI drop was higher than GI drop (23.7 [16.4-35.7] and 9.0 [6.0-12.0]; P < .01). There were correlations between the initial LI elevation and LI drop (R 2 = 0.466, P < .01) and between the LI and GI drop (R 2 = 0.263, P < .01). The LI drops significantly differed according to the different anatomical localizations by the Kruskal-Wallis test, although the GI drops did not differ (P < .01 and P = .49, respectively). CONCLUSION: LI drop was associated with initial LI elevation and was larger than GI drop. LI drop was different according to locations, although GI drop was not. These findings might indicate that LI drop would be a more sensitive marker for lesion formation than GI drop.

Blood levels of heme oxygenase-1 versus bilirubin in patients with coronary artery disease.

OBJECTIVE: Heme oxygenase-1 (HO-1) degrades heme to CO, iron, and biliverdin/bilirubin. Although serum bilirubin levels were often reported in patients with coronary artery disease (CAD), HO-1 levels in patients with CAD and the association between HO-1 and bilirubin levels have not been clarified. METHODS: We measured plasma HO-1 and serum total bilirubin levels in 262 patients undergoing coronary angiography. RESULTS: HO-1 levels were higher in patients with CAD than without CAD (median 0.46 vs. 0.35 ng/mL, P < 0.01), but bilirubin were lower in patients with CAD than without CAD (0.69 vs. 0.75 mg/dL, P < 0.02). Notably, HO-1 levels in CAD(-), 1-vessel, 2-vessel, and 3-vessel disease were 0.35, 0.51, 0.45, and 0.44 ng/mL, and were highest in 1-vessel disease (P < 0.05). Bilirubin levels in CAD(-), 1-vessel, 2-vessel, and 3-vessel disease were 0.75, 0.70, 0.68, and 0.66 mg/dL (P = NS). No correlation was found between HO-1 and bilirubin levels. In multivariate analysis, HO-1 levels were a significant factor for CAD independent of atherosclerotic risk factors and bilirulin levels. Odds ratio for CAD was 2.32 (95%CI = 1.29-4.17) for high HO-1 (>0.35 ng/mL). CONCLUSIONS: Patients with CAD were found to have high HO-1 and low bilirubin levels in blood, but no correlation was found between HO-1 and bilirubin levels.

Associations Between Plasma Betatrophin Levels and Coronary and Peripheral Artery Disease.

AIM: Betatrophin, a recently identified circulating adipokine, affects lipid and glucose metabolism. However, association between plasma betatrophin levels and atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), has not been elucidated. METHODS: We investigated plasma betatrophin levels in 457 patients undergoing elective coronary angiography who also had ankle-brachial index (ABI) test for PAD screening. RESULTS: Of the 457 study patients, CAD was present in 241 patients (53%) (1-vessel [1-VD], n=99; 2-vessel [2-VD], n=71; 3-vessel disease [3-VD], n=71). Compared to 216 patients without CAD, 241 with CAD had higher betatrophin levels (median 1120 vs. 909 pg/mL, p＜0.001). A stepwise increase in betatrophin levels was found depending on the number of ＞50% stenotic coronary vessels: 909 in CAD(-), 962 in 1-VD, 1097 in 2-VD, and 1393 pg/ml in 3-VD (p＜0.001). Betatrophin levels correlated with the number of ＞25% stenotic segments (r=0.24, p＜0.001). PAD (ABI＜0.9) was found in 41 patients (9%). Plasma betatrophin levels were also significantly higher in 41 patients with PAD than in 416 without PAD (1354 vs. 981 pg/mL, p＜0.001). In the multivariate analysis, betatrophin levels were not a factor for CAD, but they were a significant factor for 3-VD and PAD independent of atherosclerotic risk factors. The odds ratios for 3-VD and PAD were 1.06 (95%CI=1.01-1.11) and 1.07 (95%CI=1.01-1.13) for a 100-pg/mL increase in betatrophin levels, respectively (p＜0.05). CONCLUSION: Plasma betatrophin levels were associated with the presence and severity of CAD and PAD, suggesting betatrophin has a role in atherosclerosis.

Plasma Heme Oxygenase-1 Levels in Patients with Coronary and Peripheral Artery Diseases.

AIMS: Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate CO, biliverdin, and iron. Since these products have antiatherogenic properties, HO-1 may play a protective role against the progression of atherosclerosis. However, plasma HO-1 levels in patients with atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), have not been clarified yet. METHODS: We investigated plasma HO-1 levels by ELISA in 410 consecutive patients undergoing elective coronary angiography who also had an ankle-brachial index (ABI) test for PAD screening. RESULTS: Of the 410 study patients, CAD was present in 225 patients (55%) (1-vessel (1-VD), n = 91; 2-vessel (2-VD), n = 66; 3-vessel disease (3-VD), n = 68). PAD (ABI < 0.9) was found in 36 (9%) patients. Plasma HO-1 levels did not differ between 225 patients with CAD and 185 without CAD (median 0.44 versus 0.35 ng/mL), but they were significantly lower in 36 patients with PAD than in 374 without PAD (0.27 versus 0.41 ng/mL, P < 0.02). After excluding the 36 patients with PAD, HO-1 levels were significantly higher in 192 patients with CAD than in 182 without CAD (0.45 versus 0.35 ng/mL, P < 0.05). HO-1 levels in 4 groups of CAD(-), 1-VD, 2-VD, and 3-VD were 0.35, 0.49, 0.44, and 0.44 ng/mL, respectively, and were highest in 1-VD (P < 0.05). In the multivariate analysis, HO-1 levels were inversely associated with PAD, whereas they were also associated with CAD. The odds ratios for PAD and CAD were 2.12 (95% CI = 1.03-4.37) and 0.65 (95% CI = 0.42-0.99) for the HO-1 level of <0.35 ng/mL, respectively. CONCLUSIONS: Plasma HO-1 levels were found to be low in patients with PAD, in contrast to high levels in patients with CAD.

Low Plasma Levels of Fibroblast Growth Factor-21 in Patients with Peripheral Artery Disease.

AIM: Fibroblast growth factor-21 (FGF-21) is a metabolic regulator with beneficial effects on glucolipid metabolism. Since FGF-21 has lipid-lowering, anti-inflammatory and anti-oxidant properties, it may play a protective role against atherosclerosis. However, blood FGF-21 levels in coronary artery disease (CAD) or peripheral artery disease (PAD) have not been elucidated. METHODS: We measured plasma FGF-21 levels in 417 patients undergoing coronary angiography, who also had ankle-brachial index test for PAD screening. RESULTS: CAD was found in 224 patients (1-vessel [1-VD], n=92; 2-vessel [2-VD], n=65; 3-vessel disease [3-VD], n=67). No significant difference was found in the FGF-21 levels between 224 patients with CAD and 193 without CAD (median 26.0 vs. 25.9 pg/mL). FGF-21 levels in 4 groups of CAD(-), 1-VD, 2-VD, and 3-VD were 25.9, 37.2, 19.4, and 0.0 pg/mL. FGF-21 tended to be highest in 1-VD and lowest in 3-VD, but the difference did not reach statistical significance. PAD was found in 38 patients. Compared to the 379 patients without PAD, 38 with PAD had CAD more often (87% vs. 50%), especially 3-VD (P＜0.001). FGF-21 levels were lower in patients with PAD than in those without PAD (0.0 vs. 30.7 pg/mL, P＜0.02). In multivariate analysis, the FGF-21 level was an independent factor for PAD, but not for CAD. Odds ratio for PAD was 2.13 (95%CI=1.01-4.49) for a low FGF-21 level (＜15.6 pg/mL). CONCLUSION: No significant difference was found in the FGF-21 levels between patients with and without CAD. However, FGF-21 levels were low in patients with PAD, and were a factor for PAD independent of atherosclerotic risk factors.

Low Levels of Plasma Osteoglycin in Patients with Complex Coronary Lesions.

AIM: Osteoglycin is one of proteoglycans that are biologically active components of vascular extracellular matrix. However, the role of osteoglycin in atherosclerosis remains unclear. METHODS: We investigated plasma osteoglycin levels and the presence, severity, and lesion morphology of coronary artery disease (CAD) in 462 patients undergoing elective coronary angiography. RESULTS: Of 462 patients, 245 had CAD. Osteoglycin levels were higher in patients with CAD than without CAD (median 29.7 vs. 25.0 ng/mL, P＜0.05). However, osteoglycin levels did not differ among patients with one-vessel, two-vessel, or three-vessel disease (30.8, 30.6, and 29.4 ng/mL, respectively) and did not correlate with the number of stenotic segments. Among 245 CAD patients, 41 had complex coronary lesions, and 70 had total occlusion, of whom 67 had good collateralization. Between 70 patients with occlusion and 175 without occlusion, osteoglycin levels did not differ (30.4 vs. 29.5 ng/mL). Notably, osteoglycin levels were lower in 41 patients with complex lesions than in 204 without such lesions (24.2 vs. 31.6 ng/mL, P＜0.02). In multivariate analysis, osteoglycin levels were an independent factor for complex lesion but not for CAD. Odds ratio for complex lesion was 0.80 (95%CI=0.67-0.96) for each 10 ng/mL increase in osteoglycin levels (P＜0.02). CONCLUSION: Although plasma osteoglycin levels were high in patients with CAD, they did not correlate with the severity of CAD and were not an independent factor for CAD. Notably, osteoglycin levels were low in patients with complex lesions and were a factor for complex lesions, suggesting that osteoglycin plays a role in coronary plaque stabilization.