Premature Ventricular Contractions and Atrial Fibrillation: The Reunion of Distant Relatives?

The incidence and prevalence of atrial fibrillation (AF) worldwide continues to rise with aging of the population. Clinicians have been focused on prevention and identifying risk factors to better serve millions of patients affected by AF each year. ¹ Another common arrhythmia sparking interest over the past decade is premature ventricular complexes (PVCs). It is now well established that a high burden of PVCs is linked to an increased risk of cardiomyopathy and that suppression of PVCs leads to improvement in left ventricular function. ² , ³ , ⁴ Given ongoing advancements in digital health, the diagnosis of AF and the quantification of PVCs using continuous monitoring has been improved and simplified. Additionally, our heightened ability to treat both AF and PVCs safely using advanced three‐dimensional mapping technologies and radiofrequency ablation has reshaped the field of electrophysiology and improved outcomes for patients with all arrhythmias. Electrophysiologists treat and view AF and PVCs as distinct entities, but could there be a hidden and still poorly understood relationship between these common diagnoses?

A recent observational analysis by Kim et al published in 2021 was the first to suggest that the risk of new‐onset AF was higher in patients with PVCs. ⁵ In this issue of the Journal of the American Heart Association (JAHA), Lee and co‐authors describe a new association specifically between PVC burden and new‐onset AF, irrespective of sex and underlying diseases, using a single‐center, retrospective, large population‐based cohort study. ⁶ Their work showed that a moderate to high PVC burden may be an independent risk factor for AF. A large number of patients were screened (n=25 398), with 16 030 making it to their propensity‐scored matching analysis. Patients were followed for a median follow‐up of 873 days. Overall, their analyses revealed that participants with moderate to high PVC burden were at higher risk of developing new AF than the low burden PVC group (5.3% versus 2.4%, P<0.001).

Although the authors should be commended for their work, there are some important limitations and with most studies showing intriguing results, some important hypothesis‐generating questions.

The authors chose to define their PVC burden as low PVC burden as <1000/d and moderate‐to‐high PVC burden as >1000/d. Quantification of PVCs was evaluated with 24‐hour Holter 3‐channel ECG monitoring, and the indications for monitoring were report of palpitations, a clinical diagnosis of any arrhythmia, or transient loss of consciousness. First, previous literature has shown notable daily variation in PVC burden and demonstrated that up to 6 days of continuous monitoring is more accurate than the traditional 24‐hour Holter monitor. ⁷ Additionally, continuous monitoring allows clinicians to establish the percentage of PVCs over the total sinus beats during a given timeline. Second, by dichotomizing the PVC groups, the authors categorize the moderate and high group as >1000, which correlates with ≥1% burden. In fact, the overall mean burden was 4.6% (highest seen was 11.2%) in the moderate/high burden group and almost zero PVCs in the low burden group with a range of 1 to 30 PVCs seen and a mean burden of 0.01%. This would suggest that the low group was an “extremely low‐almost zero” PVCs group and the moderate to high group was a more “intermediate” group as most “high” PVCs are usually defined >15 000 to 20 000 in the literature. ⁸ This level of PVC burden would be much lower than the perceived risk of developing cardiomyopathy (24+%) and most falling in the <10% burden, which rarely leads to cardiomyopathy. ³ , ⁹ This would suggest that the number of PVCs needed to increase the risk of AF is a more intermediate range and needs to be prospectively validated in a new cohort. Correspondingly, alternative explanations need to be entertained regarding the potential mechanisms by which PVCs increase the risk of AF. As described in previous literature, one would not expect many patients with this PVC burden range to develop a cardiomyopathy. ⁹ , ¹⁰ Additionally, more research into the pro‐arrhythmogenic retrograde activation of the atria, a phenomenon rarely discussed in electrophysiology articles, as well as confounding genetic influences leading to increased risk in both arrhythmias, is needed to better understand the mechanism between PVCs and AF. ¹¹ , ¹² , ¹³

Perhaps more technical and hypothetical follow‐up questions to the study by Lee et al are regarding specific PVC characteristics. Previous research has focused on PVC characteristics to help us differentiate high‐risk features that pose a more malignant risk for cardiomyopathy including origin (epicardial), QRS width, and coupling interval. ¹⁴ , ¹⁵ Is there an association between a PVC anatomical location and new‐onset AF? Did participants with new AF and moderate to high burden of PVCs have monomorphic, or polymorphic PVCs? May there be a similar relationship with AF incidence? Although PVC anatomical location can be a point of debate among electrophysiologists, establishing a relationship between the risk of AF and PVC anatomical location would further risk stratify patients and may support screening decisions.

The authors looked at a cohort in the highest PVC burden group (defined as >10 000 a day) that received successful catheter ablation, compared them with the index study cohort with the highest PVC burden, and found a trend in lower development of AF (not statistically significant). This raises the following important key question: Could PVCs be a modifiable risk factor for AF? The authors speculate that PVC ablation may be a possible adjuvant strategy for AF ablation, which could eliminate all potential AF triggers. Without a doubt, this statement begs further data and analysis. Yet, it may influence our use of continuous monitoring post AF ablation to screen for PVCs and may represent one missing piece of the AF ablation recurrence puzzle.

The authors also briefly discuss the risk of ischemic stroke associated with PVCs. In a previous study from Liao et al published in 2012, the authors found that among normotensive patients, the diagnosis of PVCs was associated with a 2‐fold increase in the rate of incident ischemic stroke. ¹⁶ If PVCs are associated with new‐onset AF, is the risk of stroke even greater when patients have both arrhythmias? Once more, although this question requires additional data, the answer would be beneficial to assist clinicians in patient counseling when discussing anticoagulation.

Current society guidelines vary in their recommendations regarding screening of AF. The American Heart Association/American College of Cardiology have not specifically addressed screening yet, and the United States Preventive Services Task Force stated in 2022 that “current evidence is insufficient to assess the balance of benefits and harms of screening for atrial fibrillation with ECG”. ¹⁷ , ¹⁸ Clinicians use risk factor profile, in addition to symptom report, to risk stratify patients and determine appropriateness of continuous monitoring. The presence of PVCs is not an established risk factor for AF, but given these new emerging data, we may refine our initial screening strategy and pay closer attention to screening for AF in our patients with higher burden PVC. In this study, Lee et al inspire many hypotheses and raise several key questions in our quest to better understand and better serve our patients with PVCs and the associated risk of new onset AF.

Disclosures

Kurt S. Hoffmayer completed grant support from the National Institutes of Health (F32 HL10472702 and LRP) and reports consulting for Samsung Electronics, Inc., Arga Medtech Inc, and Vektor Medical, Inc. Anne‐Sophie Lacharite‐Roberge has no disclosures to report.