Different treatment options and prevention of SCD in athletes with frequent ventricular extrasystoles

Introduction

Ventricular extrasystoles (VES) can be present in the general population and also in athletes. In the general population, the percentage rate of VES ranges between 40% and 75% of healthy individuals undergoing 24-hour ambulatory electrocardiogram (Holter) monitoring. Frequent (N60/hr) or complex VES (repetitive, polymorphic, R-on-T phenomenon) occur in 1% to 4% of healthy persons [1]. However, until now, published studies that favour the occurrence of an increased number of VES in highly trained individuals vs. non-athletes are inconclusive. One study, which compared competitive athletes (n=40) to non-athletes, found premature ventricular contractions (PVCs) in 70% of athletes vs. 55% of non-athletes and complex ectopy in 25% of athletes vs. 5% of non-athletes [2]. Various other studies, however, have found PVC prevalence to be similar between athletes and non-athletic individuals [3,4].

Background

In the majority of trained athletes and/or non-athletic individuals, ventricular extrasystoles are asymptomatic and often a random finding on regular medical systematic review [3]. The morphology of PVCs most frequently originates from the right and/or left outflow tract and is a recognised idiopathic and benign entity [5,6]. However, in athletes, very frequent PVCs can be a manifestation of underlying heart disease. In a study by Biffi et al, workup revealed a structural heart disease in 30% of the high PVC group compared with 5% in the moderate group and none in the low PVC group [7]. As a result of this and several other studies with similar results, recommendations from the European Society of Cardiology (ESC) suggest thorough evaluation to rule out underlying heart disease. These evaluations should include both imaging modalities and electrophysiological assessment [8].

Recommendations

If we carefully review all of the above-mentioned information concerning VES in competitive athletes, current recommendations are only partially clear. Competitive athletes who present with less frequent PVCs (<2,000/24hr) and no exercise-induced increase of PVC or related symptoms (without or with treatment) are allowed to continue with competitive and leisure time sports. Of course, performing a yearly follow-up for re-evaluation (or earlier if symptoms reoccur) is strongly advised [9]. On the other hand, things are more complicated in athletes with more frequent PVCs (>2,000/24hr), polymorphic PVCs and increasing VES during exercise. More thorough evaluations should be initiated, including history, physical examination, echocardiography, exercise testing, and 24-hr Holter monitoring. Family history is relevant in order to exclude the presence of SCD or familial arrhythmogenic cardiac conditions, as well as the presence of symptoms, particularly during exertion. If we cannot find any structural heart disease, ESC recommendations propose 3-6 months of deconditioning (with or without medical therapy). If, after such a period, the PVCs decrease or resolve, yearly follow-ups for re-evaluation are recommended [9].

Figure 1. Recommendations from the European Society of Cardiology for participation in competitive and leisure time physical activity in patients with PVCs [8].

However, in athletes with suspected heart disease, thorough testing (such as magnetic resonance imaging [MRI], coronary angiography, endomyocardial biopsy) may be required to rule out underlying disease. Deconditioning and re-evaluation every six months is recommended [9]. As we know, the incidence of SCD is higher in competitive and leisure activity athletes. The annual incidence of SCD in young athletes (<35 years) is estimated to range from 0.7 to 3.0 per 100,000 athletes [10]. In older athletes, the incidence is higher and is expected to increase with age. The intensity of the activity and the age of the athlete are core risk factors [11].

The most frequent cause for SCD in athletes is inherited arrhythmogenic disorders (cardiomyopathies and channelopathies) and coronary artery disease (CAD) (both congenital and acquired). According to the ESC, pre-participation screening for underlying structural and/or genetic heart disease should be an effective measure [12]. This screening should be associated with the age of the athlete. In younger athletes, the focus of the screening should be inheritable cardiomyopathies and channelopathies and, in older athletes, CAD as the most common cause of SCD [13]. However, we should also bear in mind the possible setbacks of screening strategies, as the still undefined number of “false positives” misses the unknown percentage of affected cases (“false negatives”). Following this, further work is needed to collect quantitative data on the cost/benefit profile of performing electrocardiogram (ECG) screening in different populations and in different healthcare systems and settings [14].

Medical therapy, pros and cons (a way of treatment or a major headache)

Medical therapy can be used effectively for the treatment of VES in athletes as well as in non-athletes. Unfortunately, we must bear in mind that various antiarrhythmic medications have a significant potential to cause severe adverse events. Antiarrhythmic drugs have their pros and cons in relation to the type of the VES and possible underlying heart disease. In randomised clinical trials (RCTs), with the exception of beta-blockers, currently available antiarrhythmic drugs have not been shown to be effective in the primary management of patients with life-threatening ventricular tachyarrhythmias or in the prevention of SCD [14]. However, this section will focus on the medical treatment (antiarrhythmic drugs) of different types of PVCs in competitive athletes, not on primary prevention.

It is known that beta-blockers are competitive antagonists that block the receptor sites for adrenaline and noradrenalin of the sympathetic nervous system, which mediates the fight-or-flight response. Several studies have shown that intensive endurance training has shifted autonomic modulation from parasympathetic to sympathetic predominance, and of course frequent PVCs with it as a result [15]. If we believe that this could be the true mechanism of VES, then beta-blockers can occasionally reduce the percentage of PVCs. However, the mechanism of VES is often more complex; therefore, more RCTs are needed to define the right medical approach. As mentioned previously, the morphology of PVCs often suggests an origin from the right and, less frequently, left outflow tract (OT) [5,6]. Beta-blockers and verapamil (and/or a short period of deconditioning) can be very effective in the long-term management of PVCs from the OT. Of course, beta-blockers have their cons. One clinical trial explored changes in heart rate and its connection with ventricular ectopic beats. That same study showed that sinus bradycardia could facilitate the emergence of PVCs, especially in younger patients [16,17]. If this could be the potential cause (mechanism) of VES, beta-blockers and/or verapamil can only worsen the situation. Other adverse effects of using beta-blockers could be bronchospasm, hypotension, sinus bradycardia, atrioventricular (AV) block, fatigue, depression and sexual disturbances [14].

Several medications or antiarrhythmic drugs can be used for the treatment of PVCs in competitive athletes after termination of competitive sports, usually in patients with the presence of underlying structural heart disease.

It is also said that these patients should avoid any sudden bursts of activity and should have regular three- to six-month follow-ups. Amiodarone is a class III antiarrhythmic drug and one of the previously mentioned medications that can also be used for treatment of VES, especially in athletes with underlying structural heart disease, but also in athletes with PVCs in a structurally normal heart. Possible adverse effects are pulmonary fibrosis, hypothyroidism and hyperthyroidism, neuropathies, corneal deposits, photosensitivity, skin discoloration, hepatotoxicity, sinus bradycardia, QT prolongation and occasional torsade de pointes (TdP). Occasionally, studies with amiodarone have shown positive results in terms of the prevention of SCD, but this is not a consistent finding [18].

Another medication that can be used in the treatment of PVCs in athletes with underlying structural disease is disopyramide. With its negative inotropic effect on ventricular myocardium, it can be a drug of choice for PVCs in patients with hypertrophic (obstructive) cardiomyopathy (HCM). The pro-arrhythmogenic effect is a serious setback for antiarrhythmics in this group. It is worth mentioning that the class IC antiarrhythmic drugs–flecainide and propafenon - can be used for the treatment of PVCs from the OT, with a short period of deconditioning or without, with regular follow-ups during regular activities. According to the ESC guidelines for the management of ventricular arrhythmias and prevention of SCD, these drugs can be initiated in patients with more than 25% of PVCs from the OT on 24-hr Holter monitoring, especially in those with a left-sided origin [14].

Flecainide can also be proarrhythmogenic; therefore, regular ergometry tests should be made to assess QRS, QT duration and morphology. However, we should mention that, in the series by Biffi et al, the proportion of athletes with partial or complete reversal of ventricular arrhythmias was similar in those taking cardioactive drugs to those without medication [19]. It is also very important to mention drug treatment rules and regulations for athletes.

All competitive athletes are subject to the rules and regulations of the World Anti-Doping Agency.  If the medication or method an athlete requires to treat an illness or condition happens to fall under the World Anti-Doping Agency prohibited list, a therapeutic use exemption (TUE) may give that athlete the authorisation to take the needed medicine or method. However, we must add that the use of most of the effective antiarrhythmic drugs is not permitted in competitive sports.

Catheter ablation is the preferred line of therapy in athletes without underlying structural heart disease and with frequent PVCs from OT, fascicular and papillary muscle origin. It should be mentioned again that these types of VES are the most common and that catheter ablation can be very successful in these cases, with a very low complication rate in high-volume electrophysiology (EP) centres. In addition, it can be very helpful for the early restarting of regular activities in athletes [14].

Deconditioning (recommended treatment)

Biffi et al (2002) showed that intense athletic conditioning may be associated with the occurrence of frequent and/or complex ventricular tachyarrhythmias on ambulatory (Holter) ECG [7]. The series by Biffi et al demonstrated that deconditioning can reverse this process, whether or not structural cardiovascular abnormalities are present. Frequent and/or complex ventricular tachyarrhythmias, examined in 70 highly trained athletes, were particularly sensitive to short periods of deconditioning (average of 19 weeks). This included complete reversibility in about one fourth and partial reversibility in almost one half of patients [19]. We compared the results from this and several other studies on this subject, showing the effectiveness of deconditioning in highly trained athletes. Results were gained by comparing the results (PVCs, couplets and non-sustained ventricular tachycardia [NSVT]) from 24-hr Holter monitoring.

Table 1. Effects of deconditioning on premature ventricular contractions (PVCs), ventricular couplets, and bursts of non-sustained ventricular tachycardia (NSVT) in highly trained athletes. [19, 20, 21, 22]

The mechanism that explains the reduction of PVCs during the period of deconditioning can be strongly connected with the changes in the autonomic nervous system associated with high-intensity training and detraining. Intensive training has been shown to shift autonomic modulation from parasympathetic to sympathetic predominance [15], which may be a trigger for electrical instability and eventually ventricular tachyarrhythmias. To explain this possible mechanism, it may be said that during the deconditioning period in highly trained athletes there is a parasympathetic predominance. One study by Peter et al showed that parasympathetic activity is substantially greater in yoga practitioners [23]. This means that yoga can also possibly be used as a deconditioning method or even used between periods of conditioning, so that the psychological stress (disappointment) from the deconditioning period can be bypassed.

In the study by Biffi et al, deconditioning, even in athletes with underlying heart disease, reduced the number of PVCs and prevented SCD. Conversely, in athletes without cardiovascular abnormalities, the reversibility of ventricular extrasystoles (and the absence of cardiac events in the follow-up period) supports the benign clinical nature of these arrhythmias as another possible expression of an athlete’s heart [19].

Conclusion

There are various possible theories each proposing an explanation of the true mechanisms of ventricular tachyarrhythmia’s in competitive athletes. However, we also showed that most of these arrhythmias have a benign course and can be reversed. Short periods of deconditioning can be the most effective treatment for PVCs in athletes with structurally normal hearts. Of course several other options for non-invasive medical and invasive (EP) therapy can be used in the small number of athletes in whom deconditioning is not completely effective. In conclusion, more RCTs are needed so that we can completely understand the true mechanism of PVCs and plan for their treatment.