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Long-Term Effect of Continuing Sports Activity in Competitive Athletes With Frequent Ventricular Premature Complexes and Apparently Normal Heart

      The long-term outcome of athletes with frequent ventricular premature complexes (VPCs) and apparently normal heart has not been fully clarified. To evaluate the clinical and prognostic significance of VPCs and the influence of continuing sports activity during follow-up, we studied 120 healthy athletes (96 men; median age 16 years) in whom frequent VPCs (>100 VPCs/24 hours) were discovered by chance during preparticipation screening. All athletes were followed up for a median of 84 months. During follow-up, 96 underwent serial 24-hour Holter recording and 62 underwent serial echocardiography. The median number of VPCs/24 hours on basal Holter was 3,760. During follow-up, 81 athletes continued sports activity, whereas 39 did not. No athlete died or developed overt heart disease. The median number of VPCs/24 hours decreased in both athletes who continued sports activity and those who did not (from 3,805 to 1,124, p <0.0001 and from 5,787 to 1,298, p <0.0001, respectively). During follow-up, left ventricular ejection fraction slightly decreased to <55% in 9 of 62 athletes who, in respect to the remaining 53, had more VPCs/24 hours both in the basal state (12,000 vs 3,880) and during follow-up (10,702 vs 1,368), and a longer follow-up (95 vs 36 months). In conclusion, (1) frequent VPCs in athletes without heart disease have a long-term benign prognostic significance, (2) sporting activity does not modify this benign outcome, (3) during follow-up, the burden of VPCs decreases whether or not subjects continue sports activity, and (4) in 14.5% of athletes, ejection fraction slightly decreases over time.
      Frequent ventricular premature complexes (VPCs) may be discovered by chance in otherwise healthy athletes during preparticipation screening.
      • Biffi A.
      • Pelliccia A.
      • Verdile L.
      • Fernando F.
      • Spataro A.
      • Caselli S.
      • Santini M.
      • Maron B.J.
      Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes.
      • Delise P.
      • Guiducci U.
      • Zeppilli P.
      • D'Andrea L.
      • Proto C.
      • Bettini R.
      • Villella A.
      • Caselli G.
      • Giada F.
      • Pelliccia A.
      • Penco M.
      • Thiene G.
      • Notaristefano A.
      • Spataro A.
      Cardiological guidelines for competitive sport eligibility.
      • Maron B.J.
      • Zipes D.P.
      36th Bethesda Conference: eligibility recommendations for competitive athletes with cardiovascular abnormalities.
      • Pelliccia A.
      • Fagard R.
      • Bjørnstad H.H.
      • Anastassakis A.
      • Arbustini E.
      • Assanelli D.
      • Biffi A.
      • Borjesson M.
      • Carrè F.
      • Corrado D.
      • Delise P.
      • Dorwarth U.
      • Hirth A.
      • Heidbuchel H.
      • Hoffmann E.
      • Mellwig K.P.
      • Panhuyzen-Goedkoop N.
      • Pisani A.
      • Solberg E.E.
      • Van-Buuren F.
      • Vanhees L.
      Recommendations for competitive sports participation in athletes with cardiovascular disease.
      As the long-term outcome of these subjects has not been fully clarified, in this study, we evaluated their clinical prognosis and the influence of continuing sports activity on the complexity of arrhythmias during a follow-up of several years.

      Methods

      We analyzed 205 competitive athletes, <35 years old, consecutively referred to the arrhythmologic center of our division of cardiology from several sports medicine centers in Italy, after the discovery of ventricular premature beats during screening for eligibility for sport. Cases were collected from 1979 to 2008.
      In accordance with the Italian screening program, all athletes had undergone medical examination, standard 12-lead electrocardiography (ECG), and submaximal exercise testing. When enrolled in our center, all athletes underwent echocardiography, 24-hour Holter monitoring, and maximal exercise testing. Further instrumental evaluations were decided on a clinical basis.
      Forty-five subjects were excluded from the study because they presented ≥1 of the following: family history of juvenile (<40 years) sudden death or hereditary cardiomyopathies, syncope, hypertension, or any kind of heart disease such as right ventricular cardiomyopathy, mitral valve prolapse with significant valvular insufficiency, hypertrophic cardiomyopathy, or dilated cardiomyopathy. Furthermore, subjects were excluded if they had sustained (>30 seconds) ventricular tachycardia (SVT), rapid (shortest RR <300 ms) nonsustained ventricular tachycardia (NSVT), or iterative right or left ventricular outflow tract tachycardia. The criteria used for the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy, mitral valve prolapse, ventricular outflow tract tachycardia, and so forth are those commonly recommended.
      • Biffi A.
      • Maron B.J.
      • Verdile L.
      • Fernando F.
      • Spataro A.
      • Marcello G.
      • Ciardo R.
      • Ammirati F.
      • Colivicchi F.
      • Pelliccia A.
      Impact of physical deconditioning on ventricular tachyarrhythmias in trained athletes.
      • Biffi A.
      • Maron B.J.
      • Culasso F.
      • Verdile L.
      • Fernando F.
      • Di Giacinto B.
      • Di Paolo F.M.
      • Spataro A.
      • Delise P.
      • Pelliccia A.
      Patterns of ventricular tachyarrhythmias associated with training, deconditioning and retraining in elite athletes without cardiac abnormalities.
      • Corrado D.
      • Pelliccia A.
      • Heidbuchel H.
      • Sharma S.
      • Link M.
      • Basso C.
      • Biffi A.
      • Buja G.
      • Delise P.
      • Gussac I.
      • Anastasakis A.
      • Borjesson M.
      • Bjørnstad H.H.
      • Carrè F.
      • Deligiannis A.
      • Dugmore D.
      • Fagard R.
      • Hoogsteen J.
      • Mellwig K.P.
      • Panhuyzen-Goedkoop N.
      • Solberg E.
      • Vanhees L.
      • Drezner J.
      • Estes III, N.A.M.
      • Iliceto S.
      • Maron B.J.
      • Peidro R.
      • Schwartz P.J.
      • Stein R.
      • Thiene G.
      • Zeppilli P.
      • McKenna W.J.
      Recommendations for interpretation of 12 lead electrocardiogram in the athlete.
      • Ouyang F.
      • Fotuhi P.
      • Ho S.Y.
      • Hebe J.
      • Volkmer M.
      • Goya M.
      • Burns M.
      • Antz M.
      • Ernst S.
      • Cappato R.
      • Kuck K.H.
      Repetitive monomorphic ventricular tachycardia originating from the aortic sinus cusp. Electrocardiographic characterization for guiding catheter ablation.
      • Sarkozy A.
      • Brugada P.
      Sudden cardiac death and inherited arrhythmia syndromes.
      All these athletes were excluded from sport activity and entrusted to their respective clinical cardiologists.
      Of the remaining 160 athletes, 20 were excluded because they had <100 VPCs/24 hours on Holter monitoring. Another 20 were excluded because they had been enrolled <1 year before the date of the last follow-up examination. Thus, 120 athletes (96 men; median age 16 years, interquartile range [IQR] 13 to 26) took part in the study (Figure 1). Most athletes played soccer (42%); the remainder played volleyball (14%), basketball (11%), or other sports (33%). All athletes played competitively.
      Figure thumbnail gr1
      Figure 1Flow chart showing inclusion and exclusion criteria used in this study design. FU = follow-up; IQ = interquartile; SD = sudden death; VT = ventricular tachycardia.
      All had a normal electrocardiogram according to Corrado et al.
      • Corrado D.
      • Pelliccia A.
      • Heidbuchel H.
      • Sharma S.
      • Link M.
      • Basso C.
      • Biffi A.
      • Buja G.
      • Delise P.
      • Gussac I.
      • Anastasakis A.
      • Borjesson M.
      • Bjørnstad H.H.
      • Carrè F.
      • Deligiannis A.
      • Dugmore D.
      • Fagard R.
      • Hoogsteen J.
      • Mellwig K.P.
      • Panhuyzen-Goedkoop N.
      • Solberg E.
      • Vanhees L.
      • Drezner J.
      • Estes III, N.A.M.
      • Iliceto S.
      • Maron B.J.
      • Peidro R.
      • Schwartz P.J.
      • Stein R.
      • Thiene G.
      • Zeppilli P.
      • McKenna W.J.
      Recommendations for interpretation of 12 lead electrocardiogram in the athlete.
      Specifically, early repolarization patterns, negative T wave limited to V1, and high voltages in V5 and V6 in endurance athletes were regarded as normal findings. All participants also had normal echocardiogram and maximal effort test results.
      The morphology of VPCs was defined as left bundle branch block (LBBB) and right bundle branch block (RBBB)-like. In the presence of QRS duration of <0.12 second with LBBB or RBBB morphology (with or without anterior or posterior fascicular block), a fascicular morphology was defined, suggesting an origin within the conduction system (Figure 2).
      Figure thumbnail gr2
      Figure 2Different QRS morphologies encountered in the athletes studied. LBBB morphology with inferior (A) and horizontal axes (B). Fascicular morphology (C). RBBB morphology with inferior (D) and superior (E) axes.
      In subjects with >1 morphologic pattern, the prevalent morphology was considered. After evaluation, we suggested to give eligibility to sport to all athletes, on the basis of the absence of heart disease and malignant arrhythmias. However, the final decision was made by the individual sports medicine doctors who had sent us the athletes. All participants were scheduled in our center and invited to undergo periodic (if possible, annual) examinations. All athletes were called for a final clinical-instrumental examination from 2008 to 2011. All 120 subjects were available for the final clinical follow-up examination. During follow-up, 96 athletes underwent serial (≥2) 24-hour Holter recordings. In addition, 62 athletes underwent serial (≥2) echocardiography.
      Statistical analyses were made using the SYSTAT 13 (2009, Systat Software, Chicago, Illinois) packages. For continuous variables, comparisons among groups were made by Student t test or analysis of variance. Pearson chi-square test was used for categorical variables. Log transformations were used to correct for positive-skewed distributions, as appropriate. Cut-off values were obtained using receiver operating characteristic curve analysis. Data are presented as median and interquartiles for continuous measures and as proportion for categorical variables. All p values are 2-tailed, and statistical significance was established as p <0.05.

      Results

      Despite normal electrocardiogram, echocardiogram, and effort testing, generally after the enrollment during follow-up, 18 athletes (15%) underwent further instrumental examinations: cardiac magnetic resonance imaging (14) right ventricular CARTO (Biosense Webster, Yokneam, Israel) mapping (5), right ventriculography (2), and coronary angiography (2). In all cases, these additional examinations proved normal.
      Basal characteristics of Holter monitoring are listed in Table 1. In brief, the median number of VPCs/24 hours on basal 24-hour Holter monitoring was >3,700. 35.8% had couplets and 14% had NSVT. The median RR intervals of couplets and NSVT were 400 and 450 ms, respectively, whereas the shortest RR intervals were 300 and 320 ms, respectively. The median number of beats of NSVT was 4 (IQR 2 to 6).
      Table 1Basal characteristics of athletes included in the study (n = 120)
      CharacteristicValue
      No. of athletes120
      Men/Women96/24
      Age
       Median16
       IQR13–26
      VPCs/24 h
       Median3,760
       IQR1,340–8,141
      Morphology of VPCs
       LBBB (LBBB + RAD)83 (50)
       RBBB7
       Fascicular24
       Not available6
      Couplets
       No. of athletes (%)43 (35.8)
       Median/24 h in 43 athletes14
       IQR4–60
      NSVT
       No. of athletes (%)17 (14)
       Median/24 h in 17 athletes1
       IQR1–2
      RAD = right axis deviation.
      The prevalent morphology of VPCs on 12-lead electrocardiogram was precisely identified in 114 cases (Table 1). The prevalent morphology (72.8%) was LBBB, followed by fascicular morphology (21%) and RBBB (6.1%). The 2 prevalent morphologies (i.e., LBBB and fascicular) did not correlate with gender (p = 0.40 and p = 0.47, respectively), basal number of VPCs (p = 0.27 and p = 0.69, respectively), couplets (p = 0.29 and p = 0.09, respectively), or NSVT/24 hours (p = 0.20 and p = 0.23, respectively). In contrast, subjects with fascicular morphology were younger than the remaining subjects (median 13, IQR 11 to 17 vs median 17, IQR 13 to 26, p = 0.01), whereas subjects with LBBB morphology were older than the remaining subjects (median 18, IQR 13 to 27 vs median 13, IQR 11 to 18, p = 0.01).
      During effort testing at increasing loads, VPCs disappeared in 72% of cases and reappeared during recovery; in 24% of cases, VPCs remained stable during the test, whereas in 4%, they increased.
      All athletes were called for a final clinical examination.
      The median duration of clinical follow-up was 84 months (IQR 48 to 156), that is, 7 years. In 49 athletes (40.8%), follow-up continued for ≥10 years. Ninety-six athletes underwent at least 2 Holter recordings during follow-up (median 3, IQR 2 to 4). The remaining 24 subjects, after basal evaluation, declined to undergo further instrumental examinations. Among the former, the last Holter recording was performed a median of 36 months (IQR 19 to 71) after enrollment.
      Comparison between basal and last Holter recordings is listed in Table 2. In brief, the median number of VPCs/24 hours significantly decreased, and in 29 athletes (30%), VPCs either totally disappeared (12) or became sporadic (<100 ventricular premature beats/24 hours). Subjects in whom VPCs disappeared or became sporadic during follow-up did not differ significantly in terms of gender, age, morphology, or the number of VPCs on basal Holter from those who continued to have >100 VPCs/24 hours (Table 3). The only difference was the longer follow-up in the former and, obviously, the median number of VPCs/24 hours during follow-up.
      Table 2Variability of ventricular arrhythmias during follow-up in 96 athletes who underwent serial Holter recordings
      BasalFollow-Up, Median 36 mo (IQR 19–71)p
      No. of VPCs/24 h
       Median4,1981,240<0.0001
       IQR1,730–9,24315–7,255
      <100 VPCs/24 h029
      Couplets
       No. of athletes35350.15
       Median/24 h1540.63
       IQR4–601–20
      NSVT
       No. of athletes16110.31
       Median/24 h110.32
       IQR1–21–1
      The Holter data recorded at the baseline and at the end of follow-up are shown.
      Table 3Differences between subjects in whom ventricular premature complexes (VPCs) disappeared or significantly decreased (<100 VPCs/24 hours) during follow-up and subjects in whom frequent VPCs (>100 VPCs/24 hours) persisted
      CharacteristicVPCs/24 h During Follow-Upp
      <100, n = 29>100, n = 67
      Women (%)28180.28
      Age
       Median14160.55
       IQR12–2313–24
      Follow-up duration (mo)
       Median50360.02
       IQR33–8714–60
      Basal VPCs/24 h
       Median3,3004,3570.33
       IQR1,549–7,9391,760–10,232
      FU VPCs/24 h
       Median23,699<0.0001
       IQR0–111,055–9,750
      Morphology (%)
       LBBB vs all others34310.76
       Fascicular vs all others24240.97
      FU = follow-up.
      Couplets were present in the basal state and at the end of follow-up in a similar number of athletes, but the median number of couplets decreased. The number of athletes with sporadic NSVT decreased at the end of follow-up. On considering all Holter recordings, no subject developed SVT.
      Of the 96 athletes who underwent serial Holter monitoring during follow-up, 58 were still practicing sport at the time of the last Holter recording, whereas 38 had discontinued sport activity at least 4 months earlier (median 12, IQR 5 to 28).
      The trends in arrhythmias in these 2 groups of subjects, from the baseline to the end of follow-up, are listed in Table 4. From the baseline to the last Holter recording during follow-up, the median number of VPCs/24 hours significantly decreased in both athletes who continued sporting activity and those who did not (Figure 3). In addition, the percentage of subjects in whom VPCs disappeared or became sporadic (<100 VPCs/24 hours) during follow-up was similar in both groups (31% vs 29%).
      Table 4Influence of continuing sports activity on arrhythmias during follow-up
      Sport Yes (58)Sport No (38)
      BasalEnd FUpBasalEnd FUp
      No. of VPCs/24 h
       Median3,805
      Basal VPCs/24 hours: sport yes versus sport no, p = 0.67.
      1,124
      FU VPCs/24 hours: sport yes versus sport no, p = 0.69.
      <0.00015,787
      Basal VPCs/24 hours: sport yes versus sport no, p = 0.67.
      1,298
      FU VPCs/24 hours: sport yes versus sport no, p = 0.69.
      <0.0001
       IQR1,800–7,89311–7,0601,556–10,30018–7,452
      No. of athletes with <100 VPCs/24 h018
      Number of subjects with <100 VPCs/24 hours during FU: sport yes versus sport no, p = 0.82.
      (31%)
      011
      Number of subjects with <100 VPCs/24 hours during FU: sport yes versus sport no, p = 0.82.
      (29%)
      Couplets
       No. of athletes17
      Number of subjects with couplets in basal state: sport yes versus sport no, p = 0.85.
      23
      Number of subjects with couplets during FU: sport yes versus sport no, p = 0.51.
      0.1818
      Number of subjects with couplets in basal state: sport yes versus sport no, p = 0.85.
      12
      Number of subjects with couplets during FU: sport yes versus sport no, p = 0.51.
      0.35
       Median/24 h1740.521330.43
       IQR5–1011–204–311–20
      NSVT
       No. of athletes10
      Number of subjects with NSVT in basal state: sport yes versus sport no, p = 0.85.
      12
      Number of subjects with NSVT during FU: sport yes versus sport no, p = 0.81.
      0.096
      Number of subjects with NSVT in basal state: sport yes versus sport no, p = 0.85.
      4
      Number of subjects with NSVT during FU: sport yes versus sport no, p = 0.81.
      0.36
       Median/24 h110.17110.32
       IQR1–31–11–11–1
      FU = follow-up.
      Basal VPCs/24 hours: sport yes versus sport no, p = 0.67.
      FU VPCs/24 hours: sport yes versus sport no, p = 0.69.
      Number of subjects with <100 VPCs/24 hours during FU: sport yes versus sport no, p = 0.82.
      § Number of subjects with couplets in basal state: sport yes versus sport no, p = 0.85.
      Number of subjects with couplets during FU: sport yes versus sport no, p = 0.51.
      Number of subjects with NSVT in basal state: sport yes versus sport no, p = 0.85.
      ∗∗ Number of subjects with NSVT during FU: sport yes versus sport no, p = 0.81.
      Figure thumbnail gr3
      Figure 3Behavior of the median number of VPCs/24 hours during follow-up in subjects who continued sporting activity and in those who did not. The number of VPCs/24 hours decreased significantly in both groups.
      The number of patients with couplets and the number of couplets did not significantly change during follow-up in either group. Likewise, the number of patients with NSVT and the number of NSVT/24 hours did not significantly change during follow-up in either group. Sixty-two athletes underwent serial echocardiographic evaluations.
      All athletes had a normal echocardiogram in the basal state. At the last echocardiographic evaluation (after a median of 48 months, IQR 24 to 72), 53 athletes (85.5%) had a normal echocardiogram, whereas in 9 (14.5%), a reduced ejection fraction (EF; <55%) was detected (median 54%, IQR 50 to 55). All 9 of these athletes had LBBB morphology of VPCs. Four were still engaged in sports activity, whereas 5 had discontinued it.
      Comparison between athletes with a reduced EF during follow-up (n = 9) and those with a normal EF (n = 53) revealed that the number of VPCs was higher in the former both in the basal condition (median 12,000, IQR 6,928 to 18,104 vs median 3,891, IQR 1,430 to 7,919, p = 0.002) and during follow-up (median 10,702, IQR 174 to 27,150 vs median 1,368, IQR 4 to 7,518, p = 0.01; Figure 4). The best cutoffs to predict low left ventricular EF at the end of follow-up, based on receiver operating characteristic curve analysis of the number of basal and final VPCs, were 5,873 and 10,436 VPCs/24 hours, respectively (Figure 5). Finally, athletes with a reduced EF during follow-up compared with those with a normal EF were older (median 18 years, IQR 13 to 31 vs median 14 years, IQR 12 to 20, p = 0.05) and had a longer follow-up (median 96 months, IQR 53 to 157.5 vs median 72 months, IQR 51 to 123, p = 0.006).
      Figure thumbnail gr4
      Figure 4Median number of VPCs in the basal condition and during follow-up in subjects who had a normal (>55%) or abnormal (≤55%) EF at the end of follow up. FU = follow-up.
      Figure thumbnail gr5
      Figure 5Receiver operating characteristic curve analysis of basal VPCs (A) and final VPCs (B) versus low left ventricular EF at the end of follow-up. Cutoffs result respectively 5,873 VPCs/24 hours and 10,436 VPCs/24 hours.
      At the end of follow-up, 81 subjects were still practicing sporting activity, whereas 39 were not. Among the former, 33 were engaged in competitive sport, whereas 48 practiced noncompetitive but continual sporting activity (at least 3 sessions of at least 1 hour/week). The remaining 39 had discontinued sporting activity. During follow-up, no athlete died. Furthermore, no athlete presented with major arrhythmias or clinical events or developed overt heart disease.

      Discussion

      The chance discovery of frequent VPCs in competitive athletes constitutes a major problem when deciding on eligibility for sport,
      • Delise P.
      • Guiducci U.
      • Zeppilli P.
      • D'Andrea L.
      • Proto C.
      • Bettini R.
      • Villella A.
      • Caselli G.
      • Giada F.
      • Pelliccia A.
      • Penco M.
      • Thiene G.
      • Notaristefano A.
      • Spataro A.
      Cardiological guidelines for competitive sport eligibility.
      • Maron B.J.
      • Zipes D.P.
      36th Bethesda Conference: eligibility recommendations for competitive athletes with cardiovascular abnormalities.
      • Pelliccia A.
      • Fagard R.
      • Bjørnstad H.H.
      • Anastassakis A.
      • Arbustini E.
      • Assanelli D.
      • Biffi A.
      • Borjesson M.
      • Carrè F.
      • Corrado D.
      • Delise P.
      • Dorwarth U.
      • Hirth A.
      • Heidbuchel H.
      • Hoffmann E.
      • Mellwig K.P.
      • Panhuyzen-Goedkoop N.
      • Pisani A.
      • Solberg E.E.
      • Van-Buuren F.
      • Vanhees L.
      Recommendations for competitive sports participation in athletes with cardiovascular disease.
      first of all because VPCs may be a sign of an underlying dangerous heart disease of which the athletes themselves may be unaware.
      Indeed, in a series of 46 high-level symptomatic endurance athletes with frequent VPCs and/or NSVT or SVT, Heidbüchel et al
      • Heidbüchel H.
      • Hoogsteen J.
      • Fagard R.
      • Vanhees L.
      • Ector H.
      • Willems R.
      • Van Lierde J.
      High prevalence of right ventricular involvement in endurance athletes with ventricular arrhythmias. Role of an electrophysiologic study in risk stratification.
      found that 59% had a manifest ARVC and a further 30% a suspected form.
      In addition to ARVC, other structural heart diseases can be complicated by frequent VPCs: hypertrophic cardiomyopathy, acute and subacute myocarditis, dilated cardiomyopathy, and so forth.
      • Heidbüchel H.
      • Hoogsteen J.
      • Fagard R.
      • Vanhees L.
      • Ector H.
      • Willems R.
      • Van Lierde J.
      High prevalence of right ventricular involvement in endurance athletes with ventricular arrhythmias. Role of an electrophysiologic study in risk stratification.
      • Takemoto M.
      • Yoshimura H.
      • Ohba Y.
      • Matsumoto Y.
      • Yamamoto U.
      • Mohri M.
      • Yamamoto H.
      • Origuchi H.
      Radiofrequency catheter ablation of premature ventricular complexes from right ventricular outflow tract improves left ventricular dilatation and clinical status in patients without structural heart disease.
      • Taieb J.M.
      • Maury P.
      • Shah D.
      • Duparc A.
      • Galinier M.
      • Delay M.
      • Morice R.
      • Alfares A.
      • Barnay C.
      Reversal of dilated cardiomyopathy by the elimination of frequent left and right premature ventricular contractions.
      Furthermore, some channelopathies can be complicated by nonsustained ventricular arrhythmias such as long-QT syndrome, short-QT syndrome, and catecholaminergic ventricular tachycardia.
      • Sarkozy A.
      • Brugada P.
      Sudden cardiac death and inherited arrhythmia syndromes.
      Frequent VPCs arrhythmias may also be rarely observed in subjects with no apparent heart disease. According to Biffi et al,
      • Biffi A.
      • Pelliccia A.
      • Verdile L.
      • Fernando F.
      • Spataro A.
      • Caselli S.
      • Santini M.
      • Maron B.J.
      Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes.
      the prevalence of VPCs >2,000/24 hours in competitive athletes is 0.96%. Among these, some have idiopathic outflow tract ventricular tachycardia, a well-known benign arrhythmia due to automatic foci, which can be eliminated by catheter ablation.
      • Ouyang F.
      • Fotuhi P.
      • Ho S.Y.
      • Hebe J.
      • Volkmer M.
      • Goya M.
      • Burns M.
      • Antz M.
      • Ernst S.
      • Cappato R.
      • Kuck K.H.
      Repetitive monomorphic ventricular tachycardia originating from the aortic sinus cusp. Electrocardiographic characterization for guiding catheter ablation.
      However, apart from these and similar forms, in most cases, the substrate of frequent VPCs in healthy athletes is unknown.
      The discovery of frequent VPCs in otherwise healthy subjects raises many questions. The first is whether common noninvasive examinations (basal and effort ECGs and echocardiographies) are sufficient to exclude a heart disease and, further, whether, in the apparent absence of a heart disease, VPCs may be an early manifestation of a concealed evolving heart disease. The second question concerns the possibility that frequent VPCs may lead to the development of an arrhythmia-related cardiomyopathy, as suggested by some investigators.
      • Takemoto M.
      • Yoshimura H.
      • Ohba Y.
      • Matsumoto Y.
      • Yamamoto U.
      • Mohri M.
      • Yamamoto H.
      • Origuchi H.
      Radiofrequency catheter ablation of premature ventricular complexes from right ventricular outflow tract improves left ventricular dilatation and clinical status in patients without structural heart disease.
      • Taieb J.M.
      • Maury P.
      • Shah D.
      • Duparc A.
      • Galinier M.
      • Delay M.
      • Morice R.
      • Alfares A.
      • Barnay C.
      Reversal of dilated cardiomyopathy by the elimination of frequent left and right premature ventricular contractions.
      The final question is whether continuing sports activity can influence the number and complexity of VPCs, thereby increasing the risk of major ventricular arrhythmias.
      • Corrado D.
      • Basso C.
      • Rizzoli G.
      • Schiavon M.
      • Thiene G.
      Does sport activity enhance the risk of sudden death in adolescents and young adults?.
      To try to answer these questions, we analyzed 120 otherwise healthy competitive athletes with frequent VPCs, but without rapid repetitive NSVT or SVT, discovered during preparticipation screening.
      The presence of a heart disease was excluded on the basis of clinical examination and common noninvasive evaluations (basal ECG, maximal effort test, echocardiography, and Holter recording). Particular attention was paid to the basal electrocardiography, in accordance with suggestions by D. Corrado et al
      • Corrado D.
      • Pelliccia A.
      • Heidbuchel H.
      • Sharma S.
      • Link M.
      • Basso C.
      • Biffi A.
      • Buja G.
      • Delise P.
      • Gussac I.
      • Anastasakis A.
      • Borjesson M.
      • Bjørnstad H.H.
      • Carrè F.
      • Deligiannis A.
      • Dugmore D.
      • Fagard R.
      • Hoogsteen J.
      • Mellwig K.P.
      • Panhuyzen-Goedkoop N.
      • Solberg E.
      • Vanhees L.
      • Drezner J.
      • Estes III, N.A.M.
      • Iliceto S.
      • Maron B.J.
      • Peidro R.
      • Schwartz P.J.
      • Stein R.
      • Thiene G.
      • Zeppilli P.
      • McKenna W.J.
      Recommendations for interpretation of 12 lead electrocardiogram in the athlete.
      Indeed, in some heart diseases (e.g., in hypertrophic cardiomyopathy, ARVC) electrocardiographic anomalies can precede echocardiographic signs. Consequently, subjects with an anomalous ECG were excluded, even if the echocardiogram was normal. Only in a minority of cases were additional instrumental evaluations (in particular magnetic resonance imaging) performed to confirm the absence of a heart disease. The main reason is that athletes were enrolled many years ago when magnetic resonance imaging was not available.
      VPCs morphology was variable. As suggested by many investigators,
      • Biffi A.
      • Pelliccia A.
      • Verdile L.
      • Fernando F.
      • Spataro A.
      • Caselli S.
      • Santini M.
      • Maron B.J.
      Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes.
      • Corrado D.
      • Pelliccia A.
      • Heidbuchel H.
      • Sharma S.
      • Link M.
      • Basso C.
      • Biffi A.
      • Buja G.
      • Delise P.
      • Gussac I.
      • Anastasakis A.
      • Borjesson M.
      • Bjørnstad H.H.
      • Carrè F.
      • Deligiannis A.
      • Dugmore D.
      • Fagard R.
      • Hoogsteen J.
      • Mellwig K.P.
      • Panhuyzen-Goedkoop N.
      • Solberg E.
      • Vanhees L.
      • Drezner J.
      • Estes III, N.A.M.
      • Iliceto S.
      • Maron B.J.
      • Peidro R.
      • Schwartz P.J.
      • Stein R.
      • Thiene G.
      • Zeppilli P.
      • McKenna W.J.
      Recommendations for interpretation of 12 lead electrocardiogram in the athlete.
      • Rosenbaum M.B.
      Classification of ventricular extrasystoles according to form.
      • Gaita F.
      • Giustetto C.
      • Di Donna P.
      • Richiardi E.
      • Libero L.
      • Brusin M.C.
      • Molinari G.
      • Trevi G.
      Long-term follow up of right ventricular monomorphic extrasystoles.
      the most common was LBBB morphology (frequently with vertical axis), followed by fascicular and RBBB morphology.
      No athlete had any symptoms or any limitation on their sporting activity. The median number of VPCs was high (3,760/24 hour), whereas 37% also had couplets and 14% had sporadic short episodes of low-rate NSVT. In most cases, VPCs disappeared during effort.
      After our cardiologic evaluation, most athletes continued competitive or noncompetitive sporting activity. All athletes were available for a median clinical follow-up of 7 years, and 49 (40.8%) were followed up for ≥10 years. During follow-up, the median number of VPCs/24 hours significantly decreased. In 30% of cases, VPCs disappeared or became sporadic (<100 ventricular premature beats/24 hours).
      On comparing subjects who continued sporting activity with those who did not, we did not observe a different behavior in the trend of VPCs, which decreased in both groups. Furthermore, the number of subjects in whom VPCs disappeared or became sporadic was also similar in both groups (31% vs 29%).
      Clinical variables (age and gender) or the basal number of VPCs could not predict subjects in whom VPCs disappeared or became sporadic. In other words, the continuation or discontinuation of sporting activity did not influence the long-term outcome of the arrhythmic phenomenon.
      Our data are partially in contrast with those reported in 2 reports by Biffi et al
      • Biffi A.
      • Maron B.J.
      • Verdile L.
      • Fernando F.
      • Spataro A.
      • Marcello G.
      • Ciardo R.
      • Ammirati F.
      • Colivicchi F.
      • Pelliccia A.
      Impact of physical deconditioning on ventricular tachyarrhythmias in trained athletes.
      • Biffi A.
      • Maron B.J.
      • Culasso F.
      • Verdile L.
      • Fernando F.
      • Di Giacinto B.
      • Di Paolo F.M.
      • Spataro A.
      • Delise P.
      • Pelliccia A.
      Patterns of ventricular tachyarrhythmias associated with training, deconditioning and retraining in elite athletes without cardiac abnormalities.
      that suggested a proarrhythmic effect of sport. Indeed, those 2 studies found a reduction in frequent VPCs in athletes after a detraining period of 3 to 6 months and an increase in VPCs after retraining, respectively. Furthermore, they showed that, during a similar period of observation, the number of VPCs/24 hours did not change in a control group of subjects who continued sports activity.
      These data were not confirmed in a recent study by our group,
      • Delise P.
      • Lanari E.
      • Sitta N.
      • Centa M.
      • Allocca G.
      Influence of training on number and complexity of frequent VPB's in healthy athletes.
      in which, during a similar short-term period of observation, no differences emerged between deconditioned and nondeconditioned athletes. The discrepancies between our studies and those of Biffi et al
      • Biffi A.
      • Maron B.J.
      • Verdile L.
      • Fernando F.
      • Spataro A.
      • Marcello G.
      • Ciardo R.
      • Ammirati F.
      • Colivicchi F.
      • Pelliccia A.
      Impact of physical deconditioning on ventricular tachyarrhythmias in trained athletes.
      • Biffi A.
      • Maron B.J.
      • Culasso F.
      • Verdile L.
      • Fernando F.
      • Di Giacinto B.
      • Di Paolo F.M.
      • Spataro A.
      • Delise P.
      • Pelliccia A.
      Patterns of ventricular tachyarrhythmias associated with training, deconditioning and retraining in elite athletes without cardiac abnormalities.
      may be probably explained with the different populations analyzed. Indeed, we excluded from our evaluation subjects with repetitive outflow tract tachycardia, whereas these subjects were enrolled by Biffi et al. Furthermore, the study by Biffi et al
      • Biffi A.
      • Maron B.J.
      • Verdile L.
      • Fernando F.
      • Spataro A.
      • Marcello G.
      • Ciardo R.
      • Ammirati F.
      • Colivicchi F.
      • Pelliccia A.
      Impact of physical deconditioning on ventricular tachyarrhythmias in trained athletes.
      examined Olympic top-ranking athletes, whereas our study enrolled younger subjects performing competitive sports at any level. Finally, Biffi et al
      • Biffi A.
      • Maron B.J.
      • Verdile L.
      • Fernando F.
      • Spataro A.
      • Marcello G.
      • Ciardo R.
      • Ammirati F.
      • Colivicchi F.
      • Pelliccia A.
      Impact of physical deconditioning on ventricular tachyarrhythmias in trained athletes.
      studied the effect of detraining during a short-term period of few months but did not analyze the variability of the burden of VPCs over a long-term follow-up in subjects who continued or discontinued sporting activity.
      Our data suggest that, at least in our population, sport probably is not the cause of frequent VPCs in athletes. Consequently, frequent VPCs cannot be interpreted as a manifestation of athlete's heart.
      • Maron B.
      • Pelliccia A.
      The heart of trained athletes. Cardiac remodelling and the risks of sports, including sudden death.
      This conclusion is supported by not only the present data but also the observation that if frequent VPCs were a manifestation of athlete's heart they would be a common and not a rare finding.
      • Biffi A.
      • Pelliccia A.
      • Verdile L.
      • Fernando F.
      • Spataro A.
      • Caselli S.
      • Santini M.
      • Maron B.J.
      Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes.
      The reduction of VPCs over time is not easy to explain, although the phenomenon of a regression to the mean should be considered. VPCs in our population of healthy athletes appear as an isolated electric dysfunction, although a concealed disease (e.g., a subclinical myocarditis) cannot be excluded.
      The variable morphology of VPCs suggests different sites of origin: the right ventricle and particularly the right ventricular outflow tract (LBBB morphology with vertical axis), the left ventricle (RBBB morphology), or the conduction system (fascicular morphology). It follows that the substrate, and possibly the electrogenesis of VPCs in healthy athletes, is not homogenous. The younger age of subjects with fascicular VPCs suggests the possibility of increased automaticity of an immature conduction system.
      According to Biffi et al,
      • Biffi A.
      • Pelliccia A.
      • Verdile L.
      • Fernando F.
      • Spataro A.
      • Caselli S.
      • Santini M.
      • Maron B.J.
      Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes.
      we also observed a benign long-term clinical outcome. Indeed, none of our athletes had adverse events. No athlete died or presented with malignant arrhythmias and none developed overt heart disease. This favorable outcome was observed in both athletes who continued sporting activity and those who did not. This latter evaluation has not been made by other investigators.
      Despite the good clinical outcome, 14.5% of athletes developed during follow-up a reduction in EF, which however was slight (from 50% to 55%). To explain this phenomenon, we can hypothesize either an evolving cardiomyopathy (of which VPCs were an early manifestation) or an arrhythmia-related cardiomyopathy induced by VPCs.
      • Takemoto M.
      • Yoshimura H.
      • Ohba Y.
      • Matsumoto Y.
      • Yamamoto U.
      • Mohri M.
      • Yamamoto H.
      • Origuchi H.
      Radiofrequency catheter ablation of premature ventricular complexes from right ventricular outflow tract improves left ventricular dilatation and clinical status in patients without structural heart disease.
      • Taieb J.M.
      • Maury P.
      • Shah D.
      • Duparc A.
      • Galinier M.
      • Delay M.
      • Morice R.
      • Alfares A.
      • Barnay C.
      Reversal of dilated cardiomyopathy by the elimination of frequent left and right premature ventricular contractions.
      The second hypothesis is supported by the comparison between subjects who experienced this phenomenon and those who did not. Indeed, the former had a higher number of VPCs both in the basal state (about 12,000 vs 3,880/24 hours) and during follow-up (10,720 vs 1,368/24 hours). Moreover, they had a longer follow-up (95 vs 36 months). Cutoffs to predict a reduction of EF during follow-up resulted 5,873 and 10,436 VPCs/24 hours, respectively, when considering basal VPCs and VPCs during follow-up (Figure 5).
      The latter data further suggest that subjects with about 6,000 VPCs/24 hours in the basal state are at highest risk, in which during follow-up, VPCs continue to increase up to 10,000 VPCs/24 hours. As to the mechanism of this ventricular dysfunction, the LBBB morphology of VPCs suggests that the asynchronous activation of the left ventricle may play a role, as occurs in patients with LBBB or with a pacemaker with right ventricular stimulation. Finally, as 4 of these 9 subjects continued to practice sport whereas 5 did not, it follows that left ventricular dysfunction is probably not related to sporting activity.

      Disclosures

      The authors have no conflicts of interest to disclose.

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