26-A-15203-ACC RISK RECLASSIFICATION OF HEART FAILURE IN PERSISTENT ATRIAL FIBRILLATION USING DYNAMIC REGULARIZED ADAPTIVE CLUSTER OPTIMIZATION (DRACO) CMR-DERIVED LEFT VENTRICULAR EJECTION FRACTION

In this issue of the Circulation: Arrhythmia and Electrophysiology , Kurotobi et al1 determined the number of arrhythmogenic foci in atria provocable with isoproterenol infusion in patients with paroxysmal, persistent, and permanent atrial fibrillation (AF). The results show that persistent AF has more foci than paroxysmal AF. However, when AF persists for >12 months, the number of foci were reduced. The authors suggest that the increased number of foci probably is involved in the development of persistent AF. However, because this association is not observed for AF that persists for >12 months, the importance of these foci in AF maintenance remains unclear. Article see p 39 In ambulatory canine models, simultaneous sympathovagal discharges (rather than isolated sympathetic activation) are typical triggers of paroxysmal atrial tachycardia (AT) and AF.2,3⇓ These observations are explained by the late phase-3 early afterdepolarization (EAD), which depends on the coexistence of increased amplitude and duration of intracellular calcium (Cai) transient and the shortened action potential duration (APD).4,5⇓ Vagal stimulation shortens APD and therefore is needed to promote the late phase-3 EAD. In the Kurotobi study, however, arrhythmogenic foci were induced by isoproterenol alone, without the need of vagal stimulation or the use of parasympathomimetic agents. These results are different from that obtained in canine studies. The first possible explanation is that the pulmonary veins (PVs) naturally have shorter APDs with elevated (less negative) membrane potentials.6,7⇓ Rapid activation may further shorten the APD in the PVs.8 These changes are independent of the vagal tone. Jais et al9 reported the effective refractory periods of the PVs were shorter …

Knowledge of the impact of paroxysmal and persistent atrial fibrillation (AF) after catheter ablation on in-hospital outcomes and 30-day readmission remains limited. This study aimed to evaluate the procedural outcomes and 30-day readmission rates among patients with paroxysmal or persistent AF who were hospitalized for AF ablation. Using the Nationwide Readmissions Database, our study included patients aged ≥18 years with AF who were hospitalized and underwent catheter ablation during 2017-2020. Then, we compared the in-hospital procedural outcomes and 30-day readmission rates between patients with paroxysmal and persistent AF, respectively. Our study included 7310 index admissions for paroxysmal AF ablation and 9179 index admissions for persistent AF ablation. According to our analysis, there was no significant difference in procedural complications-namely, cerebrovascular accident, vascular complications, major bleeding requiring blood transfusion, phrenic nerve palsy, pericardial complications, and systemic embolization-between the persistent and paroxysmal AF groups. There was also no significant difference in early mortality between these groups (0.5% vs. 0.7%; P = .22). Persistent AF patients had significantly higher rates of prolonged index hospitalization (9.9% vs. 7.2%; P < .01) and non-home discharge (4.8% vs. 3.1%; P < .01). The 30-day readmission rates were comparable in both groups (10.0% vs. 9.5%; P = .34), with recurrent AF and heart failure being two of the most common causes of cardiac-related readmissions. Catheter ablation among hospitalized patients with paroxysmal or persistent AF resulted in no significant difference in procedural complications, early mortality, or 30-day readmission. This suggests that catheter ablation of AF can be performed with a relatively similar safety profile for both paroxysmal and persistent AF.

<i>Circulation: Arrhythmia and Electrophysiology</i> Editors’ Picks

Prevalence of Silent Cerebral Ischemia in Paroxysmal and Persistent Atrial Fibrillation and Correlation With Cognitive Function

Background and purpose Although several studies reported that stroke risk in patients with paroxysmal atrial fibrillation (AF) is similar to those with persistent or permanent AF, there is still controversy on the relationship of AF type and stroke occurrence. We investigated the effect of AF type on AF burden and stroke risk in patients with non-valvular AF. Methods Within the CODE-AF prospective, outpatient registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation), we identified 8,883 patients ≥18 years of age with non-valvular AF and eligible follow-up visits. We compared AF burden and stroke risk among patients with 3 types of AF: paroxysmal (n=5,808) or persistent (n=2,806) or permanent (n=269). Results The median age of the overall population was 68.0 (interquartile range, 60.0–75.0); 36.0% were female. Patients with persistent and permanent AF were older and had higher CHA2DS2-VASc scores and anticoagulation rate than those with paroxysmal AF. Compared with permanent AF (5.2±16.4%), the arrhythmic burden of AF on 24hrs Holter monitoring was significantly lower in paroxysmal AF (2.1±7.2%, p&lt;0.001) and persistent AF (2.0±7.5%, p&lt;0.001). During median follow-up period of 1.38 years (interquartile range: 0.96–1.67), total 82 (0.92%) patients experienced ischemic stroke with incidence rates of 0.51, 1.04 and 1.69 events per 100 person-years for paroxysmal, persistent and permanent AF, respectively. Compared with paroxysmal AF, the risk of ischemic stroke was increased in persistent AF with clinical variable adjusted hazard ratio (aHR) of 1.94 (95% confidence intervals [CI], 1.23–3.07; P=0.005) and permanent AF with aHR of 2.64 (95% CI, 1.09–6.41; P=0.03). AF type and HR of stroke occurrence Paroxysmal (n=5,808) Persistent (n=2,806) Permanent (n=269) Stoke events 39 37 6 Person years (PYs) 7673 3544 356 /100 PYs 0.51 1.04 1.69 HR (95% CI), p-value HR (95% CI), p-value HR (95% CI), p-value Unadjusted HR 1 (Reference) 2.05 (1.27–3.31), 0.003 3.32 (1.15–7.90), 0.02 Clinical variables adjusted HR 1 (Reference) 1.94 (1.23–3.07), 0.005 2.64 (1.09–6.41), 0.03 PYs: Person years; HR: Hazard ratio. Conclusion Persistent and permanent AF was associated with the increased risk of stroke than paroxysmal AF, after adjustment of clinical variables including age, sex, comorbidities and anticoagulation rate. These results suggest that AF type and burden might be related with the risk of ischemic stroke and should be considered in the stroke prevention of AF.

The dominant morphology of fractionated atrial electrograms has greater temporal stability in persistent as compared with paroxysmal atrial fibrillation

Pulmonary-vein isolation (PVI) is currently used for the treatment of chronic and paroxysmal atrial fibrillation and a major risk of PVI is thromboembolism. The purpose of this study was to observe embolic event rate in patients with persistent or paroxysmal atrial fibrillation (AF) undergone PVI. Circumferential PVI (CPVI) was performed in 64 consecutive patients with persistent AF (42 men, aged (60.0 +/- 9.1) years) and in 84 consecutive patients with paroxysmal AF (53 men, aged (61.4 +/- 9.3) years). Warfarin was administrated in all patients before ablation for at least 3 weeks ((5.2 +/- 2.6) weeks) and continued for at least 3 months post ablation with international normalized ratio (INR) of 2.0 - 3.0. During CPVI, intravenous heparin was given at a dose of 5000 - 8000 U or 75 - 100 U/kg, followed by 1000 U or 12 U/kg per hour. In patients with persistent AF, 1 patient developed embolic event during ablation and 3 patients developed embolic events after ablation. In contrast, no thromboembolic event was observed in patients with paroxysmal AF (4/64 vs 0/84, P = 0. 033). Thromboembolic event rate related to CPVI is significantly higher in patients with persistent AF than that in patients with paroxysmal AF.

This study presents an automatic diagnostic method for the discrimination between persistent and long-standing atrial fibrillation (AF) based on the surface electrocardiogram (ECG). Standard 12-lead ECG recordings were acquired in 53 patients with either persistent (N= 20) or long-standing AF (N= 33), the latter including both long-standing persistent and permanent AF. A combined frequency analysis of multiple ECG leads followed by the computation of standard complexity measures provided a method for the quantification of spatiotemporal AF organization. All possible pairs of precordial ECG leads were analysed by this method and resulting organization measures were used for automatic classification of persistent and long-standing AF signals. Correct classification rates of 84.9% were obtained, with a predictive value for long-standing AF of 93.1%. Spatiotemporal organization as measured in lateral precordial leads V5 and V6 was shown to be significantly lower during long-standing AF than persistent AF, suggesting that time-related alterations in left atrial electrical activity can be detected in the ECG. Accurate discrimination between persistent and long-standing AF based on standard surface recordings was demonstrated. This information could contribute to optimize the management of sustained AF, permitting appropriate therapeutic decisions and thereby providing substantial clinical cost savings.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): National Institute of Cardiology in Warsaw Statutory Grant Background The presence of atrial fibrillation (AF) in cardiac resynchronization therapy (CRT) recipients is common and AF is a marker of poorer CRT response. The negative influence of AF on CRT efficacy is mediated mainly by the drop of the effectively captured biventricular paced beats percentage (BiVp%) which should exceed 95-98% to warrant good CRT response. Sinus rhythm (SR) restoration may improve CRT efficacy which in turn may protect AF recurrence. However, there is lack of randomized studies comparing rhythm and rate control strategies in these patients. Purpose The purpose of the Pilot-CRAfT study (NCT01850277) was to compare the efficacy of rhythm vs rate control strategy in CRT patients with long-standing persistent or permanent atrial fibrillation. Methods The study included patients with CRT and permanent or persistent AF lasting for ≥6 months, resulting in BiVp% &amp;lt;95%, who were randomly assigned to rhythm or rate control strategy. The rhythm control strategy comprised of external electrical cardioversion (EEC). The rate control strategy included pharmacotherapy and atrioventricular node ablation (AVNA) as needed. Both of the study arms received amiodarone. The follow-up lasted 12 months. The primary endpoint was the 12-month BiVp%. The patients underwent ECHO, cardiopulmonary test, quality of live (QoL) and clinical outcomes assessment. Results The study included 43 CRT patients (97,7% males) aged 68,4 (SD: ±8,3) years with mean BiVp% 82,4% ±9,7% at baseline. The mean duration of AF paroxysm was 25 ±19 months. The mean baseline left ventricular ejection fraction (LVEF), left atrium area and maximal oxygen uptake (VO2max) were: 30 ±8%, 33 ±7 cm2, 14 ±5 mL/(kg*min), respectively. The EEC was performed in 19 out of 22 patients assigned to the rhythm control arm. The immediate success rate of EEC was 58%. 42% of the rhythm control arm patients remained in SR after 12 months. In the rate control group 1 person underwent AVNA and in 1 patient spontaneous SR resumption was observed. After 12 months there was significant BiVp% increase in both the rhythm and the rate control arms (98,1 ±2,3 vs 96,3 ±3,9%, respectively. The BiVp% differences between the groups were not significant (P = 0,093). However, in the per protocol analysis, the rhythm control group had greater LVEF after 12 months as opposed to the rate control arm (36,8% vs 29,9% respectively, P = 0,039). The LVEF raised significantly in the rhythm control group (ΔLVEF 5,0 (95%CI: 1,54; 8,46)). No significant differences between the groups in the VO2max, QoL, clinical and safety end-points were noticed. Conclusions Structured follow-up of CRT patients with long-standing persistent or permanent AF leads to significant BiVp% increase exceeding 95%. The rate control strategy did not improve CRT effectivness, irrespective of high BiVp%. However limited in the efficacy, the rhythm control strategy may improve CRT outcome in these patients, resulting in LVEF increase.

Background Atrial fibrillation (AF) is one of the commonest cardiovascular manifestations of thyrotoxicosis. A significant proportion of patients have persistent AF which may have long term consequences, for example, ischemic stroke. Methods We performed a retrospective cohort study in a regional hospital from January 2004 to June 2016 to examine the clinical characteristics and outcomes of thyrotoxic patients who presented with atrial fibrillation and to investigate possible factors associated with persistent atrial fibrillation and ischemic stoke. Results Among 1918 patients who had a diagnosis of thyrotoxicosis, 133 (6.9%) patients presented with AF. Spontaneous sinus conversion occurred in 89 (66.9%) patients in which 85 (94%) patients developed sinus conversion before or within 6 months after having achieved euthyroidism. The remaining 44 (33.1%) had persistent AF. The rate of ischemic stroke was numerically higher among patients who had persistent AF than those with spontaneous sinus conversion (15.9% versus 10.1%; log-rank 0.442, p = 0.506). Patients who sustained an ischemic stroke were older (71 ± 11 years versus 62 ± 16 years, p = 0.023) and had a trend towards higher CHA2DS2-VASc score (2.9 ± 1.7 versus 2.3 ± 1.7, p = 0.153). History of smoking (adjusted odds ratio 4.9, 95% CI [1.8,14.0], p = 0.002), a larger left atrial diameter (adjusted odd ratio 2.6, 95% CI [1.2,5.5], p = 0.014), and a relatively lower free thyroxine level at diagnosis (adjusted odd ratio 2.1, 95% CI [1.2,3.5], p = 0.008) were associated with persistence of AF on multivariate analysis. Conclusion Persistence of thyrotoxic AF occurred in one-third of patients and spontaneous sinus conversion was unlikely after six months of euthyroidism. High rate of ischemic stroke was observed among patients with persistent thyrotoxic AF and older age. Patients with factors associated with persistent AF, especially older people, should be closely monitored beyond 6 months so that anticoagulation can be initiated in a timely manner to reduce risk of ischemic stroke.

Aim . To compare the immediate and long-term efficacy of cardioversion in patients with persistent atrial fibrillation (AF) in the setting of active myocarditis versus those without myocardial inflammation. Methods . The study included 80 patients with persistent atrial AF (mean age 58.39±14.3 years; 56.2% male), of whom 40 had biopsy- or magnetic resonance imaging-confirmed myocarditis, elevated antimyocardial antibody titers, and ≥3 points on a non-invasive myocarditis diagnostic algorithm (main group). The control group (n=40) consisted of patients with non-inflammatory cardiovascular diseases (coronary artery disease, hypertension). All patients with myocarditis received standard anti-inflammatory therapy. Following pre-treatment with amiodarone for 10-12 days, electrical cardioversion (ECV) was performed. The efficacy of ECV, the need for radiofrequency ablation (RFA), the incidence of persistent AF, and adverse outcomes were evaluated. Differences were considered statistically significant at p &lt; 0.05. Results : Patients in the myocarditis group were characterized by a higher proportion of males (80.0% vs. 32.5%), younger age (49.1±12.0 vs. 67.7±9.5 years), lower left ventricular ejection fraction (LVEF) (37% [30;41] vs. 56% [52;59]), and larger left ventricular end-diastolic volume (152 ml [119;184] vs. 89 ml [76;106]), all with p &lt; 0.001. The duration of AF history and left atrial size did not differ significantly between groups. Only in the myocarditis group did spontaneous sinus rhythm (SR) restoration occur during amiodarone loading, observed in 17.5% of cases. ECV was successful on the first attempt in all patients of the control group and in 57.5% of patients with myocarditis; an additional 15% achieved SR with a second ECV attempt (p &lt; 0.001). Reversible recurrences of AF, terminated by intravenous amiodarone, were observed in 20% of myocarditis patients versus 5% in the control group (p=0.012). By the end of the one-week observation period, irreversible recurrences were recorded in two patients in each group. LVEF improved more significantly in the myocarditis group (to 42% [33;49], p &lt; 0.001). At six months post-ECV, SR was maintained in 50% of patients with myocarditis and 66.5% in the control group (p=0.530). Rhythm control was discontinued in 15% of patients with myocarditis and in 5% of the control group (p=0.547), and radiofrequency ablation was performed in 10% and 5% of patients, respectively (p=0.509). All-cause mortality was documented in 12.5% (n=5) of myocarditis patients. No thromboembolic events or heart transplantations were reported in either group. Conclusion : AF in the context of myocarditis more commonly affects individuals of working age and worsens LV systolic dysfunction. The immediate and long-term efficacy of ECV was non-significantly lower in patients with myocarditis; however, successful restoration and maintenance of SR were associated with a more pronounced improvement in LVEF, supporting the rationale for a rhythm control strategy. Further research is planned to identify predictors of sustained SR in this population.

To evaluate time course and predictors of progression of paroxysmal or persistent atrial fibrillation (AF) to permanent AF. We included 460 patients referred for paroxysmal (n= 337) or persistent (n= 123) AF between 1994 and 2012. Mean follow-up was 13.2± 6.5years. AF progression rate was 3.7% per year, 19.7% at 5years, and 38.1% at 10years. Lone AF was diagnosed in 217 patients (47%). Predictors of permanent AF were: age, persistent AF, left atrial (LA) size, left ventricular-fractional shortening (LV-FS), lack of antiarrhythmic (AA) drugs, VVI pacing (P< 0.001 for all), and valvular disease (P< 0.02). Independent predictors were age (P< 0.001), persistent AF (P< 0.001), LA diameter (P< 0.005), lack of AA drugs (P< 0.005), and VVI pacing (P< 0.01). When adjusted at means of covariates, persistent AF and age >75years remained highly significant (P< 0.01). LA dimension >50 mm was highly significant at univariate model (P< 0.001) but to a lesser extent when adjusted (P< 0.05). In patients with paroxysmal AF-with age<75years-on AA drugs, progression rate to permanent AF was 6.5% at 5years and 23.7% at 10years. Among four predictors (age, LA size, LV-FS, and VVI pacing), only age (P< 0.01) and LA size (P< 0.005) remained independently significant, but LA size was not significant when adjusted. Progression to permanent AF is a slow process. Aging, LA size, VVI pacing, lack of AA therapy, and a persistent form of AF independently increased the progression to permanent AF.

Background Catheter ablation is an established therapy for rhythm control in patients with drug-refractory atrial fibrillation (AF), however, recurrence is frequent particularly in persistent AF. There are no consistently confirmed predictors of AF recurrence after catheter ablation. The left atrial appendage (LAA) potentially plays an important role in AF recurrence, although the exact mechanism and pathophysiology are still unclear. Purpose We aimed to study whether LAA volume (LAAV) and function influence the long-term recurrence of AF after point-by-point radiofrequency catheter ablation, depending on AF type. Methods AF patients who underwent point-by-point radiofrequency catheter ablation after preprocedural cardiac computed tomography (CT) and transthoracic and transesophageal echocardiography (TEE) were included in this retrospective analysis. LAAV and LAA orifice area were measured by CT and LAA flow velocity assessed by TEE and was used as a surrogate marker of LAA function. Uni- and multivariable Cox proportional hazard regression models were performed to determine the predictors of AF recurrence. Results In total, 561 AF patients (61.9±10.2 years, 34.9% females) were included in the study. Recurrence of AF was detected in 40.8% of the cases (34.6% in patients with paroxysmal and 53.5% in those with persistent AF) with a median recurrence-free time of 22.7 [9.3–43.1] months. Patients with AF recurrence had significantly higher body surface area-indexed left atrial volume (iLAV), LAAV and LAA orifice area, as compared to those without recurrence. Moreover, patients with persistent AF had significantly higher iLAV, LAAV, LAA orifice area and lower LAA flow velocity, than those with paroxysmal AF. After adjustment for the main cardiovascular risk factors and comorbidities left ventricular ejection fraction (LVEF) &amp;lt;50% (HR=2.17; 95% CI=1.38–3.43; p&amp;lt;0.001) and LAAV (HR=1.06; 95% CI=1.01–1.12; p=0.029) were independently associated with AF recurrence in persistent AF, while no independent predictors could be identified in paroxysmal AF. Conclusions The current study demonstrates that beyond left ventricular systolic dysfunction, LAA enlargement is associated with higher rate of AF recurrence after catheter ablation in persistent AF, but not in patients with paroxysmal AF. Our results suggest that preprocedural assessment of LVEF and LAAV might contribute to optimal patient selection and aid to improve long-term results of ablation procedures in patients with persistent AF. Funding Acknowledgement Type of funding sources: None.

In Traditional Chinese Medicine, stimulation of the Neiguan spot has been utilized to treat palpitations and symptoms related to different cardiovascular diseases. We evaluated whether acupuncture might exert an antiarrhythmic effect on patients with paroxysmal or persistent atrial fibrillation (AF). Two sets of data are reviewed. The first included patients with persistent AF who underwent electrical cardioversion to restore sinus rhythm. The second included patients with symptomatic paroxysmal AF. All subjects had normal ventricular function. Acupuncture treatment consisted of 10 acupuncture sessions on a once a week basis with puncturing of the Neiguan, Shenmen and Xinshu spots. In patients with persistent AF, the recurrence rate after acupuncture treatment was similar to that observed in patients on amiodarone, but significantly smaller than that measured after sham acupuncture treatment or in the absence of any antiarrhythmic drugs. In a small group of patients with paroxysmal AF, acupuncture resulted in a significant reduction in the number and duration of symptomatic AF episodes. In conclusion, we observed that acupuncture of the Neiguan spot was associated with an antiarrhythmic effect, which was evident in patients with both persistent and paroxysmal AF. These preliminary data, observed in 2 small groups of AF patients, need to be validated in a larger population but strongly suggest that acupuncture may be an effective non-invasive and safe antiarrhythmic tool in the management of these patients.

Funding Acknowledgements Type of funding sources: None. Background Cryoballoon (CB)-guided pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). Recently, a novel balloon-guided cryothermal single shot device (POLARx) was introduced. Purpose This observational study aimed to evaluate ablation efficacy and outcome using the novel POLARx CB system compared to the established one and to access the impact of individual PV characteristics on freedom from arrhythmia recurrence in paroxysmal (PAF) and persistent (PERS) AF. Methods 666 patients undergoing CB-guided ablation for AF were included. 601 patients treated with the AFA ablation system (Arctic Front Advance Pro, AFA) were compared to 65 consecutive patients who underwent PVI using the POLARx. Individual anatomical characteristics of the left atrium and PVs were assessed using pre-procedural cardiac magnetic resonance imaging (MRI). For each PV, the cross-sectional orifice area (CSOA) was determined. Follow-up examinations were scheduled after 3 and 6 months. Results Acute PVI was achieved in all patients (100%). 6-months AF-free survival was significantly higher in the POLARx cohort (POLARx: n=45, 69%; AFA: n=359, 60%; Log-rank p=0.037*). This applies to PAF (n=42, 65%, p=0.033*), PERS (n=23, 35%, p&amp;lt;0.001*) and normal PV anatomy (2 left- and two right-sided PVs; n=57, 88%, p&amp;lt; 0.001*). MRI found a comparable percentage of patients with normal PV anatomy (POLARx: n=57, 88%; AFA: n=512, 85%, p=0.126). A higher amount of variant PV anatomy was revealed in patients with PERS AF (p=0.043*), but this factor was not predictive for AF-recurrence (PAF: p=0.610; PERS: p=0.096). PAF patients with AF-recurrence presented with significantly larger CSOA of the left sided PVs and the right superior PVs (LSPV: 224.8 ± 98.1 mm2 vs. 220.6 ± 64.8 mm2, p&amp;lt;0.001*; LIPV: 145.9 ± 63.2 mm2 vs. 140.4 ± 52.8 mm2, p&amp;lt;0.001*; RSPV 268.9 ± 79.3 mm2 vs. 262.3 ± 75.6 mm2, p&amp;lt;0.001*). In patients with PERS AF no association between CSOA and ablation outcome was observed. Multivariate Cox regression analyses identified the AFA ablation system (p=0.022*, hazard ratio (HR) 1.776, confidence interval (CI) 0.240-9.281) and PERS AF (p&amp;lt;0.001*, HR 6.608, CI 0.220-73.839) as independent predictors for AF-recurrence. Conclusion PVI using the POLARx system improves freedom from AF recurrence independent of individual anatomical considerations and PV occlusion rates. For PAF patients, a significant association between CSOA and the outcome after CB- guided PVI was demonstrated.