Premature Ventricular Complexes

Rakesh Latchamsetty and Frank Matthias Bogun

Premature ventricular contractions (PVCs) are increasingly recognized not merely as a marker of structural cardiac disease, but often as a potential cause. The decisions of when to pursue therapy to eliminate or diminish PVCs and whether to use pharmacotherapy or catheter ablation can be challenging ones. This chapter discusses the diagnosis and prognosis of frequent PVCs in the presence or absence of other structural heart disease, and describes a treatment strategy for idiopathic frequent PVCs.

Mechanism

Initiation of PVCs is dependent on the underlying cardiac substrate and, similar to other arrhythmias, can be explained by reentry, automaticity, or triggered activity. The most likely mechanism of PVCs in patients without structural heart disease is triggered activity. Reentry has been found and described in postinfarction animal models only.¹

The potential for frequent idiopathic PVCs to result in cardiomyopathy has been established on the basis of reversibility of cardiomyopathy with successful elimination of the PVCs demonstrated in observational studies. However, the mechanism responsible for development of cardiomyopathy is still under investigation. On the basis of short-term animal studies, a fibrotic process seems unlikely.² Potential mechanisms include chronic dyssynchrony and impaired Ca²⁺ homeostasis, for example, impaired Ca²⁺ handling or decreased Ca²⁺ transient.

Epidemiology

History

Irregularities in pulse and their association with poor outcomes have been hypothesized for centuries. The Chinese physician Pien Ts’Io, who lived approximately in the sixth century BC, taught that occasional pulse irregularities did not predict an adverse outcome; however, frequent irregularities (1 in 10 beats) were linked with an ominous prognosis (often resulting in death within a year).³ Reliable differentiation of PVCs from other arrhythmias became possible only in the past century. An investigation in patients with minimal or no structural heart disease demonstrated that the risk of death in patients with frequent PVCs was low.⁴ This study is often cited as showing that PVCs are benign arrhythmias. More recently, however, frequent idiopathic PVCs have been linked with a form of cardiomyopathy that can be reversed by elimination of the PVCs.^5,6

Interpreting the prevalence and frequency of PVCs is dependent on the patient population studied and the duration of monitoring. Prevalence in the normal, healthy population can range from less than 1% in healthy populations monitored for just 48 seconds ⁷ to 62% in those monitored for 6 hours.⁸ Different definitions have been used to describe the prevalence of PVCs. In patients with prior myocardial infarction, a PVC burden greater than 10 PVCs/hour was defined as frequent and was associated with increased mortality.⁹ A much higher PVC burden is required for PVC-induced cardiomyopathy.¹⁰ The prevalence of PVCs depends on the presence or absence of structural heart disease, and in healthy subjects, they have been reported to occur in up to 75% of the general population. However, in most healthy subjects, the burden is fewer than 100 PVCs/day.¹¹ A higher burden of 60 PVCs or more per hour has been described in 1% to 4% of the population.⁴ The definition of high-frequency PVCs is therefore variable and depends on the context of the patient and the purpose of evaluation.

Prognosis

Factors used to determine cardiac prognosis in patients with frequent PVCs include the presence of underlying cardiac disease and the nature of the PVCs. In postinfarction patients, predischarge documentation of more than 10 PVCs per hour correlated with increased 6-month mortality.¹² A direct link between postinfarction ventricular tachycardia (VT) and PVCs was established in a mapping study of patients with previous myocardial infarctions.¹³ PVCs were mapped to the scar, and the site of origin of the PVCs was often correlated with the VT exit site of an inducible VT. Elimination of the PVCs often permanently eliminated the VTs with the shared exit site.

Frequent PVCs (>30/hour) have been associated with increased mortality in men without coronary disease.¹⁴ The primary risk in patients with idiopathic frequent PVCs seems to be progression to cardiomyopathy rather than sudden death. Factors associated with increased risk of cardiomyopathy include frequency of PVCs, duration of PVCs, lack of symptoms, interpolation of PVCs, epicardial location, and increased PVC-QRS width.^10,15–17

Although a PVC burden of >24% has been associated with impaired left ventricular (LV) function (sensitivity 79%, specificity 78%),¹⁰ it is important to note that cardiomyopathy has also developed with considerably less frequent PVCs and has been reported with a burden as low as 4%.¹⁸ Furthermore, about 20% of patients with a PVC burden >24% did not develop cardiomyopathy.¹⁰ Therefore, factors other than the PVC burden affect the development of cardiomyopathy. Longer duration of PVCs is believed to be contributory to the development of LV dysfunction, and patients who are asymptomatic and seek medical attention later may fall victim to this scenario. Two other factors—epicardial location and an increased QRS duration (>150 milliseconds) of PVCs¹⁷—are associated with a greater likelihood of causing a cardiomyopathy; the reasons why are not definitively known but may be related to increased LV dyssynchrony associated with PVCs originating from those sites.