Do supraventricular premature beats identify patients at high risk for
atrial fibrillation?
Fiorenzo Gaita MD and Davide Castagno MD, PhD
Keywords: ablation, atrial fibrillation, premature supraventricular beats, tachyarrhythmia
Affiliation: Cardiology Unit, Citta` della Salute e della Scienza, Torino Department of Medical Science, University of Torino, Torino, Italy
Correspondence to: Fiorenzo Gaita, Cardiology Unit,
Città della Salute e della Scienza, Torino Department of Medical Science,
University of Torino, Torino, Italy. E-mail: fiorenzo.gaita@unito.it
Atrial fibrillation is the most common supraventricular arrhythmias, occurring mostly in the elderly (mean age 75 years).1 The presence of atrial fibrillation increases the thromboembolic
more invalidating outcome.4 Atrial fibrillation is also associated with a high risk of heart failure
and death and is responsible for a worsening of quality of life.5 The pathogenesis of atrial
fibrillation has been investigated for over a century but only recently significant clarifications have been brought by the advent of transcatheter ablation techniques. Under the general term of ‘atrial fibrillation’, there are a variety of different conditions ranging from ‘lone’ to ‘paroxysmal’ to ‘persistent’ atrial fibrillation that cannot be explained by a single pathogenetic mechanism.
The automaticity theory introduced by Louis in 1913, and reaffirmed by Haıssaguerre,6
recognized a triggering focus at the level of the pulmonary veins creating a supraventricular premature beat with a critical coupling necessary for the induction of atrial fibrillation.
In the 1950s, Moe introduced the multiple atrial re-entry wavelet theory. In his view, later validated by Allessie’s studies, multiple electric activation fronts advance through the atria activating contiguous atrial tissue just after the refractory period, thus creating a vicious circle.7
For the atrial fibrillation to be sustained, a critical number of simultaneous wave fronts must be present, each dependent on a critical mass of atrial tissue. Other authors8 proposed that atrial
fibrillation could be triggered by high-frequency micro re-entry localized on the atrial septum or on the left posterior atrial wall (pulmonary vein ostia). All those different mechanisms could lead alone or in combination to the various forms of atrial fibrillation. In patients with paroxysmal atrial fibrillation, without structural heart disease and with normal sized atria, the focal pulmonary veins onset seems prevalent; in persistent atrial fibrillation, often part of significant
structural heart diseases with chambers dilation and atrial remodelling, the re-entry mechanism seems more likely.
Atrial premature beats originate from an ectopic focus localized at the atrial level but outside the sinus node. The origin of atrial premature beats is related to the preceding beat, and at variance from the parasystolic beat, in which the ectopic beat is independent from the dominant rhythm. The main ECG characteristics of atrial premature beats are shown in Fig. 1: sinus P–premature P interval shorter than regular P–P interval, morphology and axis of premature P different from sinus P, postextrasystolic pause frequently noncompensatory (sinus P–premature P + postextrasystole pause inferior than two PP cycles). Atrial premature beats are common in healthy people, particularly when taking stimulating substances (caffeine and alcohol) and in the vast majority of patients with cardiac disorder. Isolated atrial premature beats are benign even when persistent. Sometimes, when the atrial premature beats are particularly frequent and occur in predisposed patients, they could originate episodes of supraventricular tachycardia (atrial fibrillation or flutter and nodal or atrioventricular re-entry tachycardia). In this case, the very short coupling interval puts the P wave on the ascending or descending branch of the T wave of the previous systole (P over T phenomenon) (Fig. 2). Very often, this kind of premature beat originates at the level of the pulmonary vein. Haıssaguerre6 demonstrated that the
radiofre-quency ablation of these ectopic foci was associated with a significant reduction in the occurrence of atrial fibrillation. Ectopic foci could originate also in other areas such as left atrial free wall, around the superior or inferior vena cava, crista terminalis, and in proximity of the coronary sinus.
It is not clear why, in human, some atrial premature beats trigger atrial fibrillation and others do not. The timing of coupling interval of premature atrial beats has a significant role in inducing atrial fibrillation. Capucci et al.9 demonstrated that premature atrial beats able to trigger atrial
fibrillation had a shorter coupling interval as compared with other isolated premature atrial beats (average 60 ms less). This characteristic did not apply to premature beats triggering atrial flutter that had a coupling interval not dissimilar from other premature beats.9
Recently, tridimensional atrial models and sophisticated computational techniques suggested that the atrial premature beats triggering atrial fibrillation have a heterogeneous dispersion of the duration of the action potential (and repolarization) in the surrounding atrial areas.10 This
phenomenon could induce conduction blocks and re-entry mechanism facilitating atrial fibrillation.
Zimmermann and Kalusche11 demonstrated that the presentation pattern of supraventricular
premature beats triggering atrial fibrillation may differ. They include sequence of short cycle/long cycle (Fig. 3a), atrial bigeminy (Fig. 3b), and sudden reduction of heart rate (Fig. 3c). In addition, from the pattern of presentation, it is clear that autonomic tone is an important factor in atrial fibrillation triggered by premature atrial beats. The heart rate variability analysis demonstrates that during the 15 min before the triggering of an atrial fibrillation episode, there is an increase in the adrenergic drive followed by marked predominance of the vagal tone immediately before the occurrence of the arrhythmia.11
Several cohort studies, during the last 25 years, asserted the role of atrial premature beats in the genesis of atrial fibrillation. Wallmann et al. reported data of 24-h Holter recording in 127
hospitalized patients after an ischemic stroke, dividing them according to the burden of atrial premature beats ( 70/24 h vs. <70/24 h). After discharge, 7-day Holter monitoring revealed that atrial fibrillation was more prevalent in patients with higher atrial arrhythmic burden (26 vs. 6.5%; P = 0.0021). The multivariate analysis, though, reveals that only the number of premature atrial beats recorded at the 24-h Holter during the hospitalization could predict the onset of paroxysmal atrial fibrillation during follow-up [odds ratio 6.6; 95% confidence interval (CI) 1.6– 28.2; P = 0.01].12
Similar results were derived from studies of patients with cryptogenic stroke. In the subanalysis of the EMBRACE study, designed to compare two ECG monitoring strategies (30 days vs. 24 h) in 572 patients with a recent cryptogenic stroke (<6 months), Gladstone et al. found that an elevated atrial arrhythmic burden recorded at the 24-h Holter during hospitalization independently predicts the occurrence of subclinical atrial fibrillation both at 30 days (P < 0.0001) and at 90 days (P = 0.0017). The probability of atrial fibrillation during follow-up was less than 9% in patients with fewer than 100 premature atrial beats/24 h, 9–24% in patients with 100–499 premature atrial beats/24 h, 25–37% in patients with 500–999 premature atrial beats/24 h, 38– 40% in patients with 1000–1499 premature atrial beats/24 h, and more than 40% in patients with more than 1500 premature atrial beats/24 h proving a dose dependence between atrial arrhythmic burden and risk of atrial fibrillation.
More recently, similar results were obtained also in the general population. In the 1429 participants of the Cardiovascular Health Study, a US study supported by the National Heart, Lung and Blood Institute, the increase in the number of premature atrial beats during the 24-h
Holter monitoring was associated with high risk of atrial fibrillation and death. The multivariate analysis demonstrated that doubling the number of premature atrial beats/h increased the atrial fibrillation risk by 17% (Hazard Ratio 1.17; 95% CI 1.13–1.22; P < 0.001) and all-cause mortality by 6% (Hazard Ratio 1.06; 95% CI 1.03–1.09; P < 0.001) during a 13-year median follow-up.13
In 2010 Binici et al. analyzed the 48-h Holter monitoring data of the Copenhagen Holter Study to investigate the association between atrial arrhythmias and incidence of atrial fibrillation, stroke, and death.
An excessive ectopic activity was defined as the presence of more than 30 atrial premature beats/h or sustain episodes of 20 or more ectopic atrial beats. At a median follow-up of approximately 6 years, an excessive ectopic activity was associated with three times the risk of hospitalization for atrial fibrillation. Furthermore, an elevated atrial arrhythmic burden was associated with an higher combined end point (stroke + death) even when patients who develop atrial fibrillation during follow-up were excluded.14 A more recent analysis on the same
population reveals that an excessive ectopic activity was associated with two times higher risk of stroke (Hazard Ratio 2.02; 95% CI 1.17–3.49). Only a minority of patients with excessive ectopic activity and stroke had a history of atrial fibrillation.15 Albeit those data are not sufficient to
establish a cause–effect relationship between premature atrial beats and stroke, they offer significant suggestion for clinical practice. An elevated atrial arrhythmic burden is associated with high risk of atrial fibrillation, thus treating premature atrial beats, particularly in patients with high thromboembolic risk, could significantly reduce the risk of cardioembolic stroke. Also, it cannot be ruled out that premature atrial beats could ‘‘per se’’ facilitate the occurrence of either atrial fibrillation or stroke. Some authors suggest that ‘atrial myopathy’, secondary to frequent
premature atrial beats, could induce cardioembolic phenomena and stroke even without atrial fibrillation. The TRENDS and ASSERT studies of patients with implantable devices (pacemakers and Implantable Cardioverter Defibrillators) did not show, in some cases, a clear temporal correlation between episodes of atrial fibrillation and stroke,16,17 generating the so-called atrial
myopathy theory. Some clinical undiagnosed condition could contribute to increase the risk of atrial arrhythmias, atrial fibrillation, and stroke. Typical example is sleep apnea syndrome that could induce an elevated atrial arrhythmic burden and increase the risk of stroke through alternative pathophysiologic mechanisms. Those complex interactions could be clarified only by well designed clinical trials.
The quantification of atrial arrhythmic burden is also useful after transcatheter ablation of atrial fibrillation. The long-term recurrence rate after pulmonary vein isolation is still high. Gang et al.18
demonstrated that frequent atrial premature beats (142 beat/24 h) could independently predict the recurrence of atrial fibrillation during a median follow-up of 4 years (Hazard Ratio 2.84; 95% CI 1.26–6.43; P = 0.01). Accordingly, monitoring premature atrial beats during the follow-up after catheter ablation procedures could be useful in minimizing recurrences.
Atrial premature beats in some circumstances are less benign than previously thought. They could be used as a low-cost marker to identify patients at high risk for atrial fibrillation and stroke regardless their pathophysiologic mechanisms.
There are no conflicts of interest.
References
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Figures and captions Fig. 1 I C1 II aVL C2 C5 III aVF C3 C6 II 25 mm/s 10 mm/mV
ECG shows sinus rhythm with at an average rate of 85 bpm and frequent premature atrial beats. The sinus P waves are normal for axis and morphology (2, 3, 5, 6, 8, 9,11, 12, and 148 beat), whereas atrial
premature beats P have different morphology and axis. Ectopic P waves are negative in II, III, aVF, V3, V4, V5, and V6 (1, 4, 7, 10, and 138 beat). The axis of the premature P waves reveals that the ectopic focus is in the inferior portion of the left atrium. Sinus PP cycle is 700 ms, premature P waves have a coupling interval (sinus P to premature P of 600 ms). The postextrasystolic pause duration (premature P sinus P interval) is 780 ms, and the sum of coupling interval þ postpremature beat pause is 1380 ms, or less than double the sinus PP interval. This pause is defined as noncompensatory and characteristic of atrial premature beats. The regular alternance of two sinus beats and an atrial premature beat is called trigeminy. From Gaita F. & Leclercq Jean F. L’interpretazione dell’ ECG. Un metodo semplice in 101 tracciati. Ed. Minerva Medica 2012.
Fig. 2
II
Atrial premature beats with P on T phenomenon. Comparing the morphology of the T wave, a morphology of the first and the second beat, the ectopic P modifies the morphology of the T wave in the second beat. Encircled in red is the ectopic P-From Gaita F. & Leclercq Jean F. L’interpretazione dell’ ECG. Un metodo semplice in 101 tracciati. Ed. Minerva Medica 2012.
Fig. 3 (a) N N N S N N N N N N N (b) S N S N S N N N N N N N (c) N N N N N N N N
