Exosomal miRNAs Differentiate Chronic Total Occlusion from Acute Myocardial Infarction.

Although coronary artery occlusion can have a negative effect on the myocardium, chronic total occlusion (CTO) exhibits different clinical features from those of acute myocardial infarction (AMI). In this study, we identify the differential associations of exosomal miRNAs with CTO and AMI. Exosomes were isolated from the plasma obtained from coronary arteries of patients undergoing percutaneous coronary intervention to treat CTO (n = 29) and AMI (n = 24), followed by small RNA sequencing, target gene predictions, and functional enrichment analyses. Promising miRNA markers were validated using real-time PCR in 35 CTO, 35 AMI, and 10 normal subjects. A total of 205 miRNAs were detected in all subjects, and 20 and 12 miRNAs were upregulated and downregulated in CTO compared to AMI patients, respectively (|fold change| > 4, FDR q < 0.05). The target genes of miRNAs that were higher in CTO patients were associated with "regulation of cell cycle phase transition", "cell growth", and "apoptosis". The target genes of miRNAs that were lower in CTO patients were enriched in terms such as "muscle cell differentiation", "response to oxygen levels", and "artery morphogenesis". On qRT-PCR analysis, the expression levels of miR-9-5p and miR-127-3p were significantly different between CTO and AMI patients. The miRNA expression levels accurately distinguished CTO from AMI patients with 79% specificity and 97% sensitivity. The miRNA contents of plasma exosomes were significantly different between CTO and AMI patients. The miRNAs may play important roles in CTO and AMI.

Comparison of the axillary venous approach and subclavian venous approach for efficacy of permanent pacemaker implantation. 8-Year follow-up results.

BACKGROUND: Long-term data on lead complication rates are limited for both the axillary and subclavian venous approaches for permanent pacemaker implantation. METHODS AND RESULTS: We conducted a single-center, retrospective, nonrandomized comparison. We reviewed the patients who had consented to receiving a permanent pacemaker implant. A superficial landmark or radiographic contrast guiding was used for the axillary venous approach, whereas conventional landmarks were used for the subclavian venous approach. From January 1992 to December 2005, we analyzed 1,161 permanent pacemaker leads in 655 patients [subclavian venous approach (group I: 338 patients, 542 leads) and axillary venous approach (group II: 317 patients, 619 leads)]. Baseline characteristics of the patients did not differ. However, DDD-pacemakers and atrial leads were used more often in group II than in group I (94% vs. 62% and 49% vs. 40%, P<0.01). During the 8-year follow-up, lead complication rates were lower in group II (17 leads, 3%) than in group I (31 leads, 6%) (P=0.03), and group II had a better complication-free survival curve than group I with a 49% relative risk reduction in lead complication rates (hazard ratio =0.51; 95% confidence interval, 0.27-0.94; P=0.03). CONCLUSIONS: The axillary venous approach for permanent pacemaker implantation has better long-term efficacy and lower lead complication rates than the subclavian venous approach.

Coronary sinus activation pattern in the differential diagnosis of regular atrial tachyarrhythmias during catheter ablation of atrial fibrillation.

BACKGROUND: Prompt diagnosis and management of atrial tachyarrhythmias (ATAs) during catheter ablation of atrial fibrillation (AF) is still challenging. METHODS AND RESULTS: In 88 patients undergoing catheter ablation of AF, 128 regular ATAs were induced or converted from AF. The coronary sinus activation time (CSAT) around the mitral annulus (MA) was measured as the difference in activation time between the most proximal and distal poles of the coronary sinus (CS) electrodes. Entrainment pacing was performed around the MA, roof area, or cavotricuspid isthmus (CTI) depending on the CSAT result. Mechanisms of tachycardias included macro-reentry around the MA (perimitral atrial flutter [PM-AFL], n=63), roof-dependent AFL (Roof-AFL, n=14), CTI-dependent AFL (CTI-AFL, n=25), and atrial tachycardia (AT, n=26). When the CSAT was ≥ 45 ms, the MA activation sequence was sequential, either proximal to distal or distal to proximal. When the CSAT was <45 ms, the MA activation sequence was mainly non-sequential with converging or diverging patterns. CSAT <45 ms was highly sensitive in ruling out PM-AFL from other left ATAs. When combined with PPI data from the MA, roof area or CTI, PM-, Roof-, CTI-AFL and AT was successfully differentiated with a high predictive accuracy. CONCLUSIONS: A diagnostic algorithm combining CSAT and entrainment pacing is helpful to assess the mechanism of ATAs during catheter ablation of AF.

Clinical efficacy of angiotensin receptor-neprilysin inhibitor in de novo heart failure with reduced ejection fraction.

BACKGROUND/AIMS: We aimed to analyze the efficacy of angiotensin receptor-neprilysin inhibitor (ARNI) by the disease course of heart failure (HF). METHODS: We evaluated 227 patients with HF in a multi-center retrospective cohort that included those with left ventricular ejection fraction (LVEF) ≤ 40% undergoing ARNI treatment. The patients were divided into patients with newly diagnosed HF with ARNI treatment initiated within 6 months of diagnosis (de novo HF group) and those who were diagnosed or admitted for HF exacerbation for more than 6 months prior to initiation of ARNI treatment (prior HF group). The primary outcome was a composite of cardiovascular death and worsening HF, including hospitalization or an emergency visit for HF aggravation within 12 months. RESULTS: No significant differences in baseline characteristics were reported between the de novo and prior HF groups. The prior HF group was significantly associated with a higher primary outcome (23.9 vs. 9.4%) than the de novo HF group (adjusted hazard ratio 2.52, 95% confidence interval 1.06-5.96, p = 0.036), although on a higher initial dose. The de novo HF group showed better LVEF improvement after 1 year (12.0% vs 7.4%, p = 0.010). Further, the discontinuation rate of diuretics after 1 year was numerically higher in the de novo group than the prior HF group (34.4 vs 18.5%, p = 0.064). CONCLUSION: The de novo HF group had a lower risk of the primary composite outcome than the prior HF group in patients with reduced ejection fraction who were treated with ARNI.

Prevalence and Characteristics of Atrial Tachycardia From Noncoronary Aortic Cusp During Atrial Fibrillation Catheter Ablation.

BACKGROUND AND OBJECTIVES: Atrial tachycardias (ATs) from noncoronary aortic cusp (NCC) uncovered after radiofrequency ablation for atrial fibrillation (AF) are rarely reported. This study was conducted to investigate the prevalence and clinical characteristics of NCC ATs detected during AF ablation and compare their characteristics with de novo NCC ATs without AF. METHODS: Consecutive patients who underwent radiofrequency catheter ablation for AF were reviewed from the multicenter AF ablation registry of 11 tertiary hospitals. The clinical and electrophysiological characteristics of NCC AT newly detected during AF ablation were compared with its comparators (de novo NCC AT ablation cases without AF). RESULTS: Among 10,178 AF cases, including 1,301 redo ablation cases, 8 (0.08%) NCC AT cases were discovered after pulmonary vein isolation (PVI; 0.07% in first ablation and 0.15% in redo ablation cases). All ATs were reproducibly inducible spontaneously or with programmed atrial stimulation without isoproterenol infusion. The P-wave morphological features of tachycardia were variable depending on the case, and most cases exhibited 1:1 atrioventricular conduction. AF recurrence rate after PVI and NCC AT successful ablation was 12.5% (1 of 8). Tachycardia cycle length was shorter than that of 17 de novo ATs from NCC (303 versus 378, p=0.012). No AV block occurred during and after successful AT ablation. CONCLUSIONS: Uncommon NCC ATs (0.08% in AF ablation cases) uncovered after PVI, showing different characteristics compared to de-novo NCC ATs, should be suspected irrespective of P-wave morphologies when AT shows broad propagation from the anterior interatrial septum.

Mechanism of regular atrial tachyarrhythmias during combined pulomonary vein isolation and complex fractionated electrogram ablation in patients with atrial fibrillation.

BACKGROUND: Atrial tachyarrhythmias (ATA) frequently develop during catheter ablation of atrial fibrillation (AF), but the mechanism of ATA during combined pulmonary vein isolation (PVI) and complex fractionated electrogram-guided ablation (CFEA) has not been reported. METHODS AND RESULTS: This study involved 105 patients with symptomatic, drug-refractory AF. After PVI, CFEA was performed in the left/right atrium if AF remained inducible in paroxysmal AF (PAF) or persisted in persistent AF (PeAF). For the 70 PAF patients, PVI alone rendered AF non-inducible in 29 patients (41.4%), and converted inducible AF into inducible atrial flutter (AFl) in 10 patients (14.3%). For the remaining 31 PAF patients, additional CFEA rendered AF non-inducible in 11 patients (15.7%), whereas only AFl was inducible in 11 patients (15.7%). For 35 PeAF patients, PVI and CFEA converted AF into sinus rhythm in 2 (5.7%) and into AFl in 21 (60.0%) patients, while AF persisted in 12 patients (34.3%). The mechanism of ATA was focal (20/114, 17.5%), roof-dependent (20/114, 17.5%), peri-mitral (33/114, 28.9%), cavotricuspid isthmus-dependent (34/114, 29.8%) AFl or unknown (7/114, 6.1%). Successful ablation was achieved in 93/114 (81.6%) tachycardias. CONCLUSIONS: The major mechanism of ATA during the combined approach of PVI and CFEA is macroreentry around large anatomic obstacles such as the pulmonary vein or the mitral or tricuspid annuli.

Transvenous Lead Extraction via the Inferior Approach Using a Gooseneck Snare versus Simple Manual Traction.

BACKGROUND AND OBJECTIVES: The number of patients with cardiac implantable electronic devices needing lead extraction is increasing for various reasons, including infections, vascular obstruction, and lead failure. We report our experience with transvenous extraction of pacemaker and defibrillator leads via the inferior approach of using a gooseneck snare as a first-line therapy and compare extraction using a gooseneck snare with extraction using simple manual traction. SUBJECTS AND METHODS: The study included 23 consecutive patients (43 leads) who underwent transvenous lead extraction using a gooseneck snare (group A) and 10 consecutive patients (17 leads) who underwent lead extraction using simple manual traction (group B). Patient characteristics, indications, and outcomes were analyzed and compared between the groups. RESULTS: The dwelling time of the leads was longer in group A (median, 121) than in group B (median, 56; p=0.000). No differences were noted in the overall procedural success rate (69.6% vs. 70%), clinical procedural success rate (82.6% vs. 90%), and lead clinical success rate (86% vs. 94.1%) between the groups. The procedural success rates according to lead type were 89.2% and 100% for pacing leads and 66.7% and 83.3% for defibrillator leads in groups A and B, respectively. Major complications were noted in 3 (mortality in 1) patients in group A and 2 patients in group B. CONCLUSION: Transvenous extraction of pacemaker leads via an inferior approach using a gooseneck snare was both safe and effective. However, stand-alone transvenous extraction of defibrillator leads using the inferior approach was suboptimal.

Electrocardiographic predictors of bradycardia-induced torsades de pointes in patients with acquired atrioventricular block.

BACKGROUND: Predictors of torsades de pointes (TdP) in bradyarrhythmia-induced acquired long QT syndrome are not well defined. OBJECTIVE: The purpose of this study was to search for electrocardiographic (ECG) TdP predictors in patients with acquired atrioventricular block (AVB) and QT prolongation. METHODS: We analyzed 12-lead ECGs from 20 patients (15 females, age 65.9 ± 15.6 years) with TdP episodes from among 898 AVB patients (2.2%) in 3 tertiary hospitals. The ECG repolarization parameters in TdP patients were compared with those of 80 age- and sex-matched control AVB patients with no TdP episodes. RESULTS: TdP was initiated by premature ventricular complexes with a long-short sequence of activation. The average cycle length of the long sequence was 1289.9 ± 228.9 ms and was 2.3 ± 0.6 times longer than the cycle length of the short sequence. TdP patients had a significantly longer mean QT interval (716.4 ± 98.9 ms vs 523.2 ± 91.3 ms, P = .001), mean T peak to end interval (334.2 ± 59.1 ms vs 144.0 ± 73.7 ms, P = .001) and a higher T peak to end interval/QT ratio (0.49 ± 0.09 vs 0.27 ± 0.11, P = .001) compared with non-TdP controls. TdP patients showed a higher prevalence of notched T waves in which T2 was at least 3 mm taller than T1 (45.0% vs 1.3%, P = .001), triphasic T waves (30.0% vs 1.3%, P = .001), reversed asymmetry (20.0% vs 0%, P = .001), and T-wave alternans (35.0% vs 0%, P = .001). An algorithm combining these morphologic parameters was able to differentiate TdP patients from non-TdP patients with high sensitivity (85.0%) and specificity (97.5%). CONCLUSION: An algorithm combining specific T-wave morphologies was useful for identifying patients with AVB who are at risk for developing TdP.

Effect of substrate modification in catheter ablation of paroxysmal atrial fibrillation: pulmonary vein isolation alone or with complex fractionated electrogram ablation.

Catheter ablation of atrial fibrillation that targets complex fractionated electrogram sites has been widely applied in the management of persistent atrial fibrillation. The clinical outcomes of pulmonary vein isolation alone and pulmonary vein isolation plus the use of complex fractionated electrogram-guided ablation (CFEA) have not been fully compared in patients with paroxysmal atrial fibrillation.This prospective study included 70 patients with symptomatic paroxysmal atrial fibrillation that remained inducible after pulmonary vein isolation. For radio-frequency catheter ablation, patients were nonrandomly assigned to a control group (pulmonary vein isolation alone, Group 1, n=35) or a CFEA group (pulmonary vein isolation plus additional CFEA, Group 2, n=35). The times to first recurrence of atrial tachyarrhythmias were compared between the 2 groups.In Group 2, CFEA rendered atrial fibrillation noninducible in 16 patients (45.7%) and converted inducible atrial fibrillation into inducible atrial flutters in 12 patients (34.3%). Atrial fibrillation remained inducible in 7 patients (20%) after the combined ablation procedures. After a mean follow-up of 23 months, freedom from recurrence of atrial tachyarrhythmias was significantly higher in Group 2 than in Group 1 (P=0.037). In Group 1, all of the recurrent tachyarrhythmias were atrial fibrillation, whereas regular tachycardia was the major mechanism of recurrent arrhythmias in Group 2 (atrial tachycardia or atrial flutter in 5 of 6 patients and atrial fibrillation in 1 patient).We found that CFEA after pulmonary vein isolation significantly reduced recurrent atrial tachyarrhythmia and might modify the pattern of arrhythmia recurrence in patients with paroxysmal atrial fibrillation.

Effect of catheter ablation on the left ventricular mass index and other echocardiograph parameters in atrial fibrillation patients: comparison with antiarrhythmic drug treatment.

BACKGROUND: Catheter ablation (CA) is reported to improve left ventricular (LV) function in patients with atrial fibrillation (AF). This study compared the effects of CA and antiarrhythmic drug treatment (AT) on LV remodeling and other echocardiography parameters in AF. METHODS: We performed a non-randomized prospective study involving 72 drug-resistant AF patients who were treated with either CA (n = 42) or who declined CA and continued on AT (n = 30). Baseline and follow-up (mean 20.7 ± 7.5 months) echocardiography was performed in all patients. The maintenance of sinus rhythm was determined based on clinical interview, electrocardiography, and 24-h Holter and event recording. RESULTS: There were no significant differences between the two groups in regard to demographic features, blood pressure, and medication. CA was superior to AT with respect to sinus rhythm maintenance, LV ejection fraction, left atrium (LA) diameter, and LA volume index. In addition, CA resulted in decreases in the LV mass [from 190.5 ± 36.1 to 179.3 ± 32.4 g (p = 0.02)] and the LV mass index [from 104.2 ± 20.5 to 98.2 ± 18.3 g/m(2) (p = 0.03)]. No parameter improved in AT patients. These improved echocardiographic parameters were observed in both groups with maintained sinus rhythm. CONCLUSION: Reverse LV remodeling after CA may include a reduction in the LV mass index, which appears to be associated with sinus rhythm maintenance.