Frequent ventricular extrasystoles: significance, prognosis and treatment

It is a relatively common occurrence for cardiovascular clinicians to see patients with frequent premature ventricular contractions. They may appear in patients without any overt cardiovascular disease, in which case pathogenesis can be considered idiopathic. However, although largely asymptomatic, patients with PVCs can experience upsetting symptoms, and there are occasions when the presence of PVCs signifies susceptibility towards more sinister arrhythmias, especially when heart disease is present. Premature ventricular contraction in certain patients is triggered by the same mechanisms that give rise to ventricular tachycardia, which may be cured with catheter ablation. Appropriate clinical evaluation and investigations are important in assessing patients so that effective treatment can be targeted.

I - Prevalence and Prognosis

Premature ventricular contractions have been described in 1% of clinically normal people as detected by a standard ECG and 40–75% of apparently healthy persons as detected by 24–48 hour ambulatory (Holter) ECG recordings. Kennedy et al demonstrated that frequent (>60/h or 1/min) and complex PVCs could occur in apparently healthy subjects, with an estimated prevalence of 1–4% of the general population.(1) Further to demonstrationg that frequent and complex ventricular ectopy could occur in healthy subjects, they also showed it could be associated with a benign prognosis.
Additionaly, both the incidence and complexity of PVCs is increased in almost all heart disease, and could be 90% in coronary artery disease and dilated cardiomyopathy. (2,3) Other studies such as MRFIT (4) and data from the Framingham Heart Study (5) have linked the frequent occurrence of PVCs with an increased risk of sudden cardiac death and death from any cause. However, these studies have been criticised for the lack of rigorous measures to exclude underlying heart disease confounded, which can halve the outcome regarding death.
These irregularities did not interfere with normal lifespan when they were occasional, but an ominous prognosis was implied if they were frequent. This was shown to be so in more recent times where patients who have had a myocardial infarction were more prone to sudden death if they had frequent PVCs (5).
Nevertheless, recent studies have documented that the LV dysfunction in patients with frequent PVCs could recover after elimination of the PVCs by medical treatment or catheter ablation therapy in certain cases. (6-10)

II - Clinical Features

The length and morphology of PVCs are highly variable and depend on the place of origin, the presence of structural heart disease and treatment with antiarrhythmic drugs. In general, QRS duration is mostly longer than 120 ms because the activation spread occurs from a ventricle to the contralateral one through the nonspecialised myocardium (figure 1). However, when activation comes from one of the fascicles through a specific conduction system, both ventricles could be activated 'synchronously', which may result in a QRS complex of less than 120 ms. (11)
Premature ventricular contractions can be classified in various ways, depending on: 1) coupling interval (early and delayed); 2) QRS duration (wide and narrow); 3) morphology; and 4) complexity. The morphology of PVCs is of great importance in patients susceptible to being treated by catheter ablation because the 12-lead EKG can identify the origin of PVCs with a certain degree of precision. As a general rule, PVCs originating in the left ventricle have right bundle branch block morphology, and PVCs originating in the right ventricle have a left bundle branch block pattern.
Frequent PVCs can also be observed in patients with hypertension. (12) In the MRFIT population cohort of over 10, 000 men aged 35-57 years, the level of systolic blood pressure was linked with the prevalence of PVCs. More recent data in the Atherosclerosis Risk in Communities (ARIC) Study (13) of more than 15,000 white and African- American men and women presented extended findings that showed frequent or complex PVCs that are also associated with hypertension. The Framingham Heart Study has indicated that patients with left ventricular hypertrophy by electrocardiographic criteria are at greater risk of sudden death and acute myocardial infarction than subjects with a normal heart. The ARIC Study also demonstrated that the prevalence of PVCs Increases with the electrocardiographic Increases of left ventricular mass.

In some cases, PVCs may be the first manifestation of underlying structural heart disease. For this reason, in all patients with PVCs, the clinician must perform a detailed clinical history of 12-lead EKG and chest X-ray. Although the relationship between frequent PVCs originating from the ventricular outflow tract and arrhythmogenic right ventricular cardiomyopathy was once suggested. (14) The indication of a record EKG-Holter, a stress test or echocardiogram, depends on whether PVCs persist after the initial evaluation of suspected structural heart disease or the development of complex forms of ventricular arrhythmias.
For more than 20 years now, it has been accepted that the presence of PVCs in the absence of structural heart disease entails a favorable benign prognosis, even when they arise frequently. For this reason and because of the proarrhythmic potential of antiarrhythmic drugs (see later), the physician does not need to treat PVCs in this clinical setting, except when the PVCs are responsible for many symptoms. Nevertheless, in some cases very frequent PVCs can produce ventricular dilation and dysfunction (tachycardiomyopathy), the latter being an indication for treatment (ablation or antiarrhythmic drugs), even in the absence of symptoms. However, the clinical importance of frequent PVCs in patients without any LV dysfunction is still unclear.
The prognostic significance of PVCs in ischemic heart disease is less benign. Indeed, in patients who have suffered a myocardial infarction, the presence of PVCs has been associated with an increase of up to three times the risk of sudden death. (2,3,15)

There are conflicting results as to the meaning of PVCs in stress testing. Frolkis et al. demonstrated that the presence of frequent PVCs during recovery from exercise testing is a better predictor of the risk of sudden death than the isolated presence of PVCs reached during the effort. (16)
Caffeine is a central stimulant which can increase sympathetic activity. Clinical impressions and anecdotes that often associate arrhythmias with consumption of caffeine, alcohol and tobacco have been widely practised in managing patients with palpitations despite the relative lack of direct evidence. Animal studies have shown that caffeine administration at high doses could induce and increase the frequency of PVCs. Some epidemiological data exist with an association between PVCs activity and caffeine intake, but experimental human studies have not produced consistent results to establish this link.

III - Management

The thinking behind the necessity to suppress PVCs was studied in the Cardiac Arrhythmia Suppression Trial (CAST).(17) This study hypothesised that the suppression of asymptomatic PVCs, or minimally symptomatic after myocardial infarction, would reduce arrhythmic deaths. The authors concluded that treatment with Flecainide and Encainide was an independent risk factor for arrhythmic cause death, cardiac death and non-arrhythmic mortality. This excess mortality was independent of time post-AMI. This further study highlights the proarrhythmic effect of these drugs in patients with heart disease and disputes the notion of using drugs simply for the sake of suppressing PVCs.

PVCs originating from the RVOT have been associated with malignant ventricular arrhythmias. The ability of frequent PVCs originating from a focal source in triggering idiopathic ventricular fibrillation (VF) in seemingly normal hearts was first reported by Haissaguerre et al. (18) The PVCs were mapped to sites at the RVOT and also along the distal Purkinje system in both left and right ventricles. Catheter ablation was shown to be effective in acutely eliminating VEBs and reducing the incidence of further VF recurrence. Similar triggers have been shown in selected patients with long QT and Brugada syndromes with reports of successful elimination of PVCs with catheter ablation. Further studies in large numbers of patients with longer follow-up are required to assess the full prognostic benefit of this approach. Progressive PVCs are induced with exercise or stress which can cause syncope or sudden death with polymorphic VT or VF. Treatment is usually with b blockers and ICD implantation.

Summary of the treatment of patients with premature ventricular contractions (PVCs) (19)

1. Ventricular ectopic beats (PVCs) are frequently seen in daily clinical practice and are usually benign.
2. Presence of heart disease should be sought and, if absent, indicates good prognosis in patients with PVCs.
3. There is no clear evidence that caffeine restriction is effective in reducing PVCs frequency, but patients with excessive caffeine intake should be cautioned and appropriately advised if symptomatic with PVCs.
4. Unifocal PVCs arising from the right ventricular outflow tract are common and may increase with exercise and cause non-sustained or sustained ventricular tachycardia. Catheter ablation is effective and safe treatment for these patients.
5. B-blockers may be used for symptom control in patients where PVCs arise from multiple sites. It should also be considered in patients with impaired ventricular systolic function and/or heart failure.
6. Risk of sudden cardiac death from malignant ventricular arrhythmia should be considered in patients with heart disease who have frequent PVCs. An implantable cardioverter defibrillator may be indicated if risk stratification criteria are met.
7. PVCs have also been shown to trigger malignant ventricular arrhythmias in certain patients with idiopathic ventricular fibrillation and other syndromes. Catheter ablation may be considered in some patients as adjunctive treatment.

Figure 1 : 55-year-old patient with frequent and asymptomatic premature ventricular contractions.

Conclusion:

It is a relatively common occurrence for cardiovascular clinicians to see patients with frequent premature ventricular contractions. Frequent and apparently idiopathic PVCs are usually considered a benign condition that can be managed with conservative measures. B-blockers are usually very effective. Radiofrequency catheter ablation has generally been reserved for patients with frequent PVCs whose quality of life is disturbed by bothersome symptoms, or for patients with sustained VT. Most of the remaining patients exhibit no severe clinical symptoms, and so the condition of those patients with frequent PVCs without any overt symptoms is believed to be relatively benign.