AF = atrial fibrillation; CV = cardiovascular; ECG = electrocardiography; ECV = electrical cardioversion; HR = hazard ratio; ICM = insertable cardiac monitor; MPI =myocardial performance index;OSA = obstructive sleep apnoea; PVI = pulmonary vein isolation;RF = radiofrequency; TAVI = transcatheter aortic valve implantation

In this issue:

Abbreviations used in this issue:

Current and future AF prevalence in Australia

Oral anticoagulation after RF ablation and thromboembolism/bleeding risks

Digoxin increases mortality in anticoagulated AF

Vitamin D deficiency and AF

Accuracy of ECG diagnostic methods of AF

OSA and AF outcomes

AF with severe aortic stenosis undergoing TAVI

Hybrid procedure and P-wave duration for AF ablation

Regular atrial tachycardias following PVI for paroxysmal AF

MPI in AF treated with amiodarone after ECV

Submuscular ICM implantation improves AF detection

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Independent commentary by Dr Andrei Catanchin, a cardiologist/electrophysiologist specialising in the management of AF and other arrhythmias in private practice in Melbourne. Dr Catanchin has a particular expertise in the management of AF and other rhythm disorders. In addition to practising general cardiology, he performs catheter ablation for AF and other arrhythmias, implants pacemakers and ICDs (defibrillators) and his research interests include alternatives to warfarin in AF management.

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Welcome to the twentieth issue of Atrial Fibrillation Research Review.This month’s issue includes a study reporting a relatively low risk of thromboembolism >3 months following RF (radiofrequency) ablation for AF compared with nonablated patients. A review of studies exploring the relationship between vitamin D status and AF has reported conflicting findings. Data from ORBIT-AF participants with AF have shown that those who also have OSA (obstructive sleep apnoea) have worse symptoms and are more likely to need hospitalisation, but are not more likely to experience major CV events or AF progression, or to die. This issue concludes with research reporting better AF detection by ICMs (insertable cardiac monitors) when the device is implanted subpectorally rather than subcutaneously.

I hope you find the papers selected for this issue of interest, and I am always happy to receive your comments, feedback and suggestions.

Kind Regards,

Dr Andrei Catanchinandrei.catanchin@researchreview.com.au

Estimating the current and future prevalence of atrial fibrillation in the Australian adult populationAuthors: Ball J et al.

Summary: These authors estimated the prevalence of AF in 2014 and predicted future prevalences to 2034 using international AF prevalence statistics and population projections. The estimated prevalence of AF among Australians aged ≥55 years at June 2014 was 5.97% for men and 4.79% for women, and assuming no significant changes in the natural history of AF, the projected respective estimated prevalences by 2034 would be 7.22% and 5.64%. Furthermore, it is expected that there will be an increase in prevalence in the Queensland region of ~2-fold by 2034, which will be the greatest regional increase, followed by a projected 1.7-fold increase in New South Wales. The authors also projected 2- and 2.5-fold increases among older individuals and men aged ≥85 years, respectively, by 2034.

Comment: This eye-opening estimate reminds us of the rapidly growing burden of AF and highlights the need for systematic screening in order to offer adequate treatment, particularly in stroke prevention.

Reference: Med J Aust 2015;202(1):32–5Abstract

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Vitamin D deficiency and atrial fibrillationAuthors: Thompson J et al.

Summary: These authors identified six studies specifically investigating vitamin D status in patients with AF, and found equivocal results from three studies reporting a positive association between vitamin D deficiency and AF, one study reporting an association between elevated vitamin D levels and AF, and two suggesting no relationship. The study designs were incomparable and had methodological limitations that impeded the interpretation of current evidence, and the authors concluded that work taking into account considerations that they raise is needed to clarify the relationship between vitamin D status and AF.

Comment: Given the high incidence of both AF and vitamin D deficiency (particularly in the elderly), it will be challenging to demonstrate a clear relationship, even in large studies, but AF appears to be yet another reason to treat low vitamin D levels. The exact target levels are another matter for discussion.

Reference: Int J Cardiol; Published online Feb 10, 2015Abstract

Oral anticoagulation therapy after radiofrequency ablation of atrial fibrillation and the risk of thromboembolism and serious bleedingAuthors: Karasoy D et al.Summary: The risks of oral anticoagulant-associated thromboembolism and serious bleeding >3 months after first-time RF ablation of AF were explored in 4050 Danish registry patients. The thromboembolism rate over median 3.4 years was 1.8%, with no difference in incidence rates between oral anticoagulant recipients and nonrecipients; oral anticoagulation discontinuation remained insignificant in a multivariable analysis. The serious bleeding rate beyond 3 months after RF ablation was 2.1%, and the risk was significantly greater among oral anticoagulant recipients (HR 2.05 [95% CI 1.25–3.35]). Among 15,848 nonablated matched patients with AF who received rhythm control therapy, the thromboembolic rate was lower among oral anticoagulant recipients versus nonrecipients (1.34 vs. 2.14), but the incidence was lower among patients who received RF ablation (adjusted incidence rate ratio 0.53 [95% CI 0.43–0.65]).

Comment: This paper supports the current guidelines recommending up to 3 months anticoagulation for all patients after AF ablation. Following this, the decision on longer term anticoagulation needs to be based on the CHADSVASC score and also taking into consideration the bleeding risk.

Reference: Eur Heart J 2015;36(5):307–15Abstract

Digoxin treatment is associated with increased total and cardiovascular mortality in anticoagulated patients with atrial fibrillationAuthors: Pastori D et al.Summary: These researchers prospectively explored the relationship between digoxin use and mortality in 815 consecutive patients with nonvalvular AF treated with vitamin K antagonists and followed for a median 33.2 months (2460 person-years). Compared with participants not receiving digoxin, those who were receiving digoxin (n=171) were older, had a clinical history of heart failure and were at higher risk of a thromboembolic event. Time spent in therapeutic range did not differ between digoxin recipients and nonrecipients, but digoxin recipients had a significantly greater total mortality rate (p<0.001). A multivariate analysis showed that digoxin use was significantly associated with total and CV-related mortality (respective HRs 2.224 [p<0.001] and 4.686 [p<0.001]); these associations were confirmed in a propensity score-matched analysis.

Comment: This is a prospective study (rather than the observational retrospective analyses we have previously reviewed). It, too, showed generally increased CV and total mortality (×4 and ×2 respectively) in those patients treated with digoxin, even after best efforts to account for confounding variables – subjects on digoxin were older and ‘sicker’, which reflects clinical practice. All were anticoagulated.

Reference: Int J Cardiol 2015;180:1–5Abstract

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Impact of hybrid procedure on P wave duration for atrial fibrillation ablationAuthors: Kumar N et al.

Summary: These authors reported on 41 patients with AF who underwent a first ablation with the hybrid procedure, which involves epicardial isolation of the pulmonary vein and posterior wall of the left atrium and endocardial checking of lesions and touch-ups as required. They also utilised a new automated method for estimating P-wave segmentation and duration from recognisable P-waves in ECG lead I or II before and after the hybrid procedure, based on fitting of each P-wave using two Gaussian functions. Compared with preprocedure, postprocedure P-wave duration was significantly decreased (84.77 vs. 104.4 msec [p=0.0151]), especially in patients with persistent AF (85.6 vs. 122.4 msec [p=0.02]), and this significant difference persisted at 9 months in 12 patients with persistent AF without recurrence. P-wave duration was also significantly higher before the procedure in patients with persistent AF than in those with paroxysmal AF (122.4 vs. 92.5 msec [p=0.0383]), and significantly decreased after the procedure in prior electrical cardioverted patients (84.7 vs. 106.7 msec [p=0.0353]).

Comment: P-wave duration is a marker of atrial electrical disease, so is longer in patients with more advanced AF, shortens with ablation and appears to be a marker of procedural success.

Reference: J Interv Card Electrophysiol 2015;42(2):91–9Abstract

Regular atrial tachycardias following pulmonary vein isolation for paroxysmal atrial fibrillation: a retrospective comparison between the cryoballoon and conventional focal tip radiofrequency techniquesAuthors: Juliá J et al.

Summary: These researchers compared the incidences and mechanisms of postablation regular atrial tachycardias in consecutive patients with paroxysmal AF undergoing a first PVI procedure using circumferential point-by-point RF (n=186) or first-generation (n=59) or second-generation (n=41) cryoballoon ablation. Compared with cryoballoon ablation, PVI using point-by-point RF was associated with a significantly higher incidence of regular atrial tachycardias (11.3% vs. 3.0% [p=0.028]), but the difference was significant only for second-generation cryoballoon ablation when the two types were analysed separately (the respective incidences of regular atrial tachycardias with first- and second-generation cryoballoon ablation were 5.1% and 0.0%).

Comment: We will see a growing number of publications comparing cryoballoon ablation of AF with the traditional RF-based approach. Among the many advantages of the balloon approach is, as demonstrated in this study, less ablation-induced tachycardia.

Reference: J Interv Card Electrophysiol 2015;42(2):161–9Abstract

Accuracy of methods for diagnosing atrial fibrillation using 12-lead ECGAuthors: Taggar JS et al.

Summary: This was a systematic review and meta-analysis of ten studies investigating 16 methods for interpreting a total of 55,376 participant ECGs. It was found that nine methods used by automated software (eight studies) had respective sensitivity and specificity values for diagnosing AF of 0.89 and 0.99, with respective positive and negative likelihood ratios of 96.6 and 0.11. When compared with software, interpretation using seven methods performed by healthcare professionals (five studies) yielded similar sensitivity (0.92) but lower specificity and positive and negative likelihood ratios (0.93, 13.9 and 0.09, respectively). Subgroup analyses of primary care professionals revealed that compared with nurses, ECG interpretation by general practitioners was associated with better sensitivity (0.91 vs. 0.88) and specificity (0.96 vs. 0.85).

Comment: With the rapidly climbing prevalence of AF, screening is likely to be incorporated into health guidelines in the future, and improved methods of detecting this arrhythmia more accurately are required. This study shows that the automated ECG reading software selected is very sensitive and highly specific.

Reference: Int J Cardiol; Published online Feb 9, 2015Abstract

Impact of obstructive sleep apnea and continuous positive airway pressure therapy on outcomes in patients with atrial fibrillationAuthors: Holmqvist F et al., on behalf of the ORBIT-AF Investigators

Summary: This paper reported the results of 10,132 ORBIT-AF participants with AF followed for ≤2 years, focussing on the impact of OSA (n=1841) on major CV outcomes. A greater proportion of participants with versus without OSA had severe disabling symptoms (22% vs. 16% [p<0.0001]) and were receiving rhythm control therapy (35% vs. 31% [p=0.0037]), and they were at significantly increased risk of hospitalisation (adjusted HR 1.12 [95% CI 1.03–1.22]), but not death (0.94 [0.77–1.15]), the composite of CV death, myocardial infarction and stroke/transient ischaemic attack (1.07 [0.85–1.34]), major bleeding (1.18 [0.96–1.46]) or AF progression (1.06 [0.89–1.28]). Participants receiving continuous positive airway pressure therapy for OSA were significantly less likely to progress to more permanent forms of AF than those not receiving such therapy (adjusted HR 0.66 [95% CI 0.46–0.94]).

Comment: The link between OSA and AF is well accepted and OSA makes rhythm control more challenging, but its effective management can ameliorate symptoms, reduce AF burden, slow the progression of AF and improve rhythm control overall. It is interesting to note in this study that the major clinical endpoints were similar between OSA and non-OSA patients. Surprisingly, OSA did not appear to accelerate progression of AF, but its effective management did slow progression.

Reference: Am Heart J; Published online Feb 5, 2015Abstract

Predictors and clinical implications of atrial fibrillation in patients with severe aortic stenosis undergoing transcatheter aortic valve implantationAuthors: Barbash IM et al.

Summary: This research in 371 consecutive patients with symptomatic, severe aortic stenosis undergoing TAVI (transcatheter aortic valve implantation), including 143 with AF at baseline, assessed AF postprocedural incidence and its clinical impact. Compared with patients with no AF at baseline, those who did had similar procedural and hospital outcomes, but higher 1-year mortality (28.8% vs. 18% [p=0.01]). Among patients without baseline AF, new postprocedural AF occurred in 20% during their hospital stay and was associated with a statistically nonsignificant doubling of the in-hospital mortality rate (13% vs. 6.7% [p=0.22]). Independent predictors of new AF were haemodynamic instability during TAVI (odds ratio 9.3 [95% CI 1.5–59]) and transapical access (4.96 [1.9–13.2]).

Comment: Not surprisingly in elderly patients with severe aortic stenosis, 39% had AF at baseline and one-fifth of patients developed new AF postprocedure, the latter prolonging and complicating their hospital admission.

Reference: Catheter Cardiovasc Interv 2015;85(3):468–77Abstract

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Improvement of the myocardial performance index in atrial fibrillation patients treated with amiodarone after cardioversionAuthors: Besli F et al.

Summary: Response to ECV (electrical cardioversion) after amiodarone 1g and its effects on MPI (myocardial performance index) were evaluated in 103 patients with persistent or long-standing persistent AF. Sinus rhythm was restored in 72.8% of participants, and persisted at 1 month in 69.3%. The MPI for all participants was 0.73. Left atrium size was found to independently predict sinus rhythm maintenance at 1 month. Subgroup analyses revealed a significant decrease in MPI when pre-ECV echocardiographic findings and those at 1 month were compared in participants with maintained sinus rhythm (0.66 vs. 0.56 [p<0.001]).

Comment: This study demonstrated several points we already know about AF; e.g., duration of AF and atrial size are predictors of successful rhythm control, be it by chemical or ECV. Additionally, it showed improvements in various parameters of atrial and ventricular function (systolic and diastolic) with maintenance of sinus rhythm with cardioversion and amiodarone.

Reference: J Interv Card Electrophysiol 2015;42(2):107–15Abstract

Submuscular implantation of insertable cardiac monitors improves the reliability of detection of atrial fibrillationAuthors: Bergau L et al.

Summary: This was an analysis of retrospective data from patients who underwent PVI for AF (50% paroxysmal) and who had ICMs implanted either subcutaneously and parasternally (n=14) or under the left major pectoral muscle (n=16). Compared with participants who had ICMs implanted subcutaneously, those with subpectorally implanted ICMs had a significantly higher R-wave amplitude. There were 1024 episodes detected as AF in 670 transmitted protocols. The rate of correct AF recognition was significantly greater in participants with subpectorally implanted ICMs than in those with subcutaneously implanted ICMs (85% vs. 54% [p=0.03]). Sinus rhythm with misinterpreted artefacts accounted for the remaining episodes in both groups.

Comment: Monitoring for AF is a rapidly growing and very important area, and the new monitors offer a minimally invasive way in which to achieve this. Although deep implantation appears to offer more accurate recording and interpretation, this comes at a cost in terms of procedural discomfort and complexity.

Reference: J Interv Card Electrophysiol 2015;42(2):143–9Abstract

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