Premature ventricular complexes (PVCs) constitute one of the most common arrhythmias encountered in clinical practice. Contemporary data suggest an increasing incidence of idiopathic PVCs, defined as PVCs without apparent structural heart disease [1]. The prevalence of PVCs is proportional to the monitoring duration. A study among 122 043 US Air Force personnel demonstrated at least 1 PVC in 8 per 1000 participants, during a 48-s ECG recording [2]. PVCs were detected in 5.5% of participants in the Atherosclerosis Risk in Communities (ARIC) study, based on a 2 min ECG [3].

Notably, there are no epidemiological data on the prevalence high burden (>5 or 10%) idiopathic (i.e., without concomitant structural heart disease) PVCs in random Holter monitoring data. When 24 h Holter monitoring was implemented among healthy adults, 69% of participants had at least one PVC, with a median PVC count of 2 and a 95th percentile of 193 PVCs [4]. In a population of 1424 community-dwelling individuals who underwent Holter monitoring, increasing age, smoking status, elevated systolic blood pressure, and impaired left ventricular ejection fraction were independently associated with increased PVC frequency [5]. Even though most patients with PVCs experience no symptoms, PVC-related symptoms can lead to worsened quality-of-life and include palpitations, chest discomfort and dizziness [6]. Interestingly, periods of bigeminy and trigeminy appear most commonly during rest and cause pseudo-bradycardia or, more accurately, bradysphygmia and subsequent fatigue since PVCs often do not generate peripheral pulse and impair cardiac output.

Regarding asymptomatic idiopathic PVCs natural history, the existing body of literature provides discordant findings. Day-by-day fluctuations in PVC burden have been reported in patients undergoing 14-day monitoring, but most data are based on 24 h recordings [7].

Gaita et al. [8] reported that among 55 patients who were followed up for 15 years, PVCs spontaneously resolved in half of them. Similarly, among a paediatric population without structural heart disease, PVCs resolved during follow-up in 28% of patients (estimated mean time to disappearance 115 months) [9]. Lee et al. more recently reported spontaneous remission in 44% of study population, at a median follow-up time of 15.4 months [10]. Gatzoulis et al. reported similar rates of satisfactory response between antiarrhythmic drug recipients (82%) and non-recipients (86%), among idiopathic RVOT symptomatic patients [11].

In contrast, no significant change in PVC prevalence was reported in 239 asymptomatic patients with normal left ventricle, over 5.6 years [12]. It should be noted that this study included patients with an initially diagnosed high PVC burden of 10%. Initiation point of follow-up is crucial since increased PVC burden is usually asymptomatic and remission, if ever occurring, this will take place in the first months.

PVCs have consistently been associated with adverse cardiovascular outcomes among patients with pre-existing structural heart disease. The association between PVCs and increased mortality in the context of ischemic heart disease is well established, as numerous historical studies provide relevant data ^[13][14][15][13,14,15]. Initial efforts for pharmacological suppression of PVCs in survivors of myocardial infarction, using class IC antiarrhythmics, led to detrimental effects on total mortality [16], now known to stem from the untoward interplay between abnormal substrate (scar and ischemia) and pharmacodynamics of this particular class. Concerning non-ischemic systolic heart failure, a sub-group analysis of the DANISH study, among patients with left ventricle ejection fraction (LVEF) ≤ 35%, high PVC burden (defined as more than 30 PVCs per hour) was associated with a 38% higher risk of death from any cause and a 78% higher risk of cardiovascular mortality [17].

The association between the presence of PVCs in patients with apparently normal hearts and adverse cardiovascular outcomes has been a matter of debate. A hallmark study in 1985 reported no difference in prognosis between 70 asymptomatic, healthy participants with ventricular ectopy and the general population [18]. In the first meta-analysis of prospective cohort studies of participants without clinically apparent heart disease, the presence of PVCs was associated with worse cardiovascular outcomes [19]. However, the exclusion of structural heart disease was not based on advanced tests, and the risk was also correlated with presence of cardiovascular risk factors.

The Cardiovascular Health Study (CHS) was a landmark study of 1429 24 h ambulatory ECG recipients that demonstrated a 31% increased risk of death and a 48% increased risk for incident heart failure in the upper quartile of PVC frequency compared to those in the lowest quartile [20].

In the context of resolving this discrepancy, cardiac magnetic resonance (CMR) has emerged as a pivotal tool in the assessment of PVCs prognosis. In a cohort of 518 patients in whom PVCs were deemed as asymptomatic after negative routine diagnostic workup, subjects with myocardial abnormalities on CMR were at increased risk for the composite outcome of sudden cardiac death, resuscitated cardiac arrest and episodes of ventricular fibrillation-ventricular tachycardia [21]. Patients with multifocal PVCs and non-left bundle branch block morphology had increased incidence of abnormal CMR findings.

In the modern era, an absence of structural heart disease has to be confirmed by CMR. In a single-center prospective study of patients with significant PVC burden, (>1.000 but <10.000, or presence of NSVT) and normal findings at echocardiography, structural heart disease was diagnosed in 25.5% (mostly myocarditis) and non-specific abnormal findings were present in 20% [22].

The mechanism of idiopathic frequent PVCs is not related to myocardial scarring, suggesting either an increased triggered activity or the presence of a micro-reentry ^[23][24][23,24]—also explaining the tendency to flare up during lower heart rates. The sites of successful catheter ablation of idiopathic PVC origins have been progressively elucidated and include both the endocardium and, less commonly, the epicardium. Idiopathic PVCs usually originate from specific anatomical structures such as the ventricular outflow tracts, aortic root, atrioventricular annuli, papillary muscles, Purkinje network, and exhibit characteristic electrocardiograms based on their anatomical background [25].

With respect to PVCs originating specifically from the right ventricular outflow tract, subclinical myocarditis not detectable with current CMR techniques seems to be the underlying mechanism. In the case of aortic root, extensive fibrous tissue presents between the base the cusps and LV myocardium appears as the most plausible factor [26].

An increasing body of evidence has revealed that frequent PVCs can lead to impairment of ventricular function (PVC-induced cardiomyopathy), which is a potentially reversible condition after PVC elimination [27]. PVC burden has been shown to be the strongest independent predictor of PVC-induced cardiomyopathy in several studies ^[27][28][29][27,28,29].

The cut-off value that separates those at high risk of PVC-induced cardiomyopathy ranges from 16% to 26%, in different studies ^[29][30][31][29,30,31]. Current guidelines report that a PVC burden of 10% seems to be the minimal threshold for development of LV dysfunction, with higher risk when the PVC burden is >20% ^[27][29][27,29].

Other risk factors include PVC-QRS width of >150 ms [32], asymptomatic status [33], and interpolated PVCs [34]. Male sex and epicardial origin of the arrhythmia are also independent predictors of PVC-induced myocardial dysfunction [35]. Elimination of PVCs often leads to improvement or resolution of cardiomyopathy ^[29][31][29,31]. Interestingly, therapeutic benefit of PVC suppression extends to patients with concomitant, but causally unrelated, structural heart disease [36]. A wider QRS during SR is a poor prognostic marker for EF recovery following PVC catheter ablation [37].