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Relation Between Training-Induced Left Ventricular Hypertrophy and Risk for Ventricular Tachyarrhythmias in Elite Athletes
Relation Between Training-Induced Left Ventricular Hypertrophy and Risk for Ventricular Tachyarrhythmias in Elite Athletes Alessandro Biffi, MDa,*, Barry J. Maron, MDb, Barbara Di Giacinto, MDa, Paolo Porcacchia, MDa, Luisa Verdile, MDa, Fredrick Fernando, MDa, Antonio Spataro, MDa, Francesco Culasso, MDc, Maurizio Casasco, MDa, and Antonio Pelliccia, MDa The aim of this study was to analyze the relation between the magnitude of traininginduced left ventricular (LV) hypertrophy and the frequency and complexity of ventricular tachyarrhythmias in a large population of elite athletes without cardiovascular abnormalities. Ventricular tachyarrhythmias are a common finding in athletes, but it is unresolved as to whether the presence or magnitude of LV hypertrophy is a determinant of these arrhythmias in athletes without cardiovascular abnormalities. From 738 athletes examined at a national center for the evaluation of elite Italian athletes, 175 consecutive elite athletes with 24-hour ambulatory (Holter) electrocardiographic recordings (but without cardiovascular abnormalities and symptoms) were selected for the study group. Echocardiographic studies were performed during periods of peak training. Athletes were arbitrarily divided into 4 groups according to the frequency and complexity of ventricular arrhythmias during Holter electrocardiographic monitoring. No statistically significant relation was evident between LV mass (or mass index) and the grade or frequency of ventricular tachyarrhythmias. In addition, a trend was noted in those athletes with the most frequent and complex ventricular ectopy toward lower calculated LV mass. In conclusion, ventricular ectopy in elite athletes is not directly related to the magnitude of physiologic LV hypertrophy. These data offer a measure of clinical reassurance regarding the benign nature of ventricular tachyarrhythmias in elite athletes and the expression of athlete’s heart. © 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;101:1792–1795) Left ventricular (LV) hypertrophy as a consequence of intense and systematic physical training is a common and prominent feature of “athlete’s heart” syndrome.1,2 Such LV hypertrophy evident in athletes is adaptive and reversible with deconditioning.3 Frequent and complex ventricular tachyarrhythmias on ambulatory (Holter) electrocardiography are also part of the clinical constellation of athlete’s heart.4 However, it is unresolved as to why only some athletes without cardiovascular disease express ventricular arrhythmias during Holter monitoring (about 30%), whereas most (about 70%) do not,5 and whether the magnitude of training-induced LV hypertrophy is a determinant of these arrhythmias. Therefore, in the present study, we analyzed a large population of elite athletes without evidence of cardiovascular disease to assess the relation between traininginduced LV hypertrophy (as assessed by echocardiography) and the frequency and complexity of ventricular tachyarrhythmias identified during 24-hour ambulatory (Holter) electrocardiographic monitoring.
a Institute of Sports Medicine and Science, Italian Olympic Committee, Rome, Italy; bHypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota; and cUniversity of Rome “La Sapienza,” Department of Statistics, Rome, Italy. Manuscript received October 9, 2007; revised manuscript received and accepted February 10, 2008. *Corresponding author: Tel: 39-06-3685-9185; fax 39-06-4746050. E-mail address: [email protected] (A. Biffi).
0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2008.02.081
Methods From May 2005 to February 2006, 738 athletes were examined at the Institute of Sports Medicine and Science in Rome, a national center for the evaluation of elite Italian athletes. Of the 738 athletes, 175 were selected for the study group on the basis of the absence of cardiovascular abnormalities and/or symptoms and elite levels of training and competition (Olympic or world-class athletes). Cardiovascular evaluation was performed during periods of peak training. Each athlete was studied during a 24-hour period of ambulatory (Holter) electrocardiographic monitoring, which included a conditioning session (an average of 1 hour in duration), consistent with that usually performed by the athlete. The remaining time was occupied by usual daily activities, which could include noncompetitive and recreational physical activities. No athlete was taking antiarrhythmic or other cardioactive medications. All athletes underwent routine screening for performance-enhancing drugs in accord with the World Anti-Doping Agency list6 of the International Olympic Committee (including steroids, amphetamines, cocaine, growth hormone, and erythropoietin), with negative results. The mean age of the athletes was 23 ⫾ 6 years (range 15 to 43), and 108 (62%) were male. Subjects were engaged in 35 sports, most commonly rowing (n ⫽ 24 [14%]), track and field (n ⫽ 20 [11%]), and swimming (n ⫽ 16 [9%]). Echocardiographic studies were performed using a Hewlett-Packard 77020 AC (Hewlett-Packard Corporation, Palo Alto, California) or a Sonos 5500 (Philips Medical Systems, Andover, Massachusetts). Images of the heart www.AJConline.org
Miscellaneous/Athlete’s Heart and Ventricular Arrhythmias
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Table 1 Demographic, clinical, and echocardiographic data from 175 elite athletes with ambulatory Holter electrocardiograms Variable
Age (yrs) Men/women Heart rate at rest (beats/min) PVCs Couplets NSVT Ventricular septum (mm) Posterior wall thickness (mm) LV end diastolic diameter (mm) LV mass (g) LV mass index (g/m2)
Total (n ⫽ 175)
23.6 ⫾ 6 108/67 48.8 ⫾ 6 802 ⫾ 2,308 23 (13%) 8 (5%) 9.4 ⫾ 1.3 9.2 ⫾ 1.2 53.6 ⫾ 5 92 ⫾ 57 99 ⫾ 21
PVCs
p Value
Group A 0 (n ⫽ 40)
Group B 1–100 (n ⫽ 71)
Group C 101–1,000 (n ⫽ 33)
Group D ⬎1,000 (n ⫽ 31)
23.4 ⫾ 5.4 23/17 49.3 ⫾ 5.5 0 0 0 9.4 ⫾ 1.4 9.3 ⫾ 1.3 52.9 ⫾ 4.1 188 ⫾ 56 98.5 ⫾ 21
24.1 ⫾ 6.1 42/29 47.4 ⫾ 5.4 21 ⫾ 27 5 (7%) 4 (5%) 9.4 ⫾ 1.7 9.4 ⫾ 1.3 53.7 ⫾ 5.7 195 ⫾ 66 100 ⫾ 24
23.8 ⫾ 6 21/12 49.6 ⫾ 7 364 ⫾ 254 9 (28%) 2 (6%) 9.5 ⫾ 1 9.2 ⫾ 1.1 53.6 ⫾ 5.3 191 ⫾ 19 99 ⫾ 19
23.1 ⫾ 5.5 22/9 48.6 ⫾ 5.1 4.390 ⫾ 4.116 9 (30%) 2 (7%) 9.3 ⫾ 1.1 8.93 ⫾ 1 54.5 ⫾ 3.9 188 ⫾ 43 98 ⫾ 19
0.41 0.01* 0.62 0.001 0.01† 0.89 0.11 0.10 0.12 0.59 0.62
Data are expressed as mean ⫾ SD or as number (percentage). * Groups A and B versus group D. † Groups C and D versus groups A and B.
were obtained in multiple cross-sectional planes using standard transducer positions. LV cavity dimensions, anterior ventricular septal and posterior free wall thicknesses, and left atrial dimensions were obtained from M-mode echocardiograms. To enhance the accuracy of LV wall thickness measurements, these dimensions were verified from the 2-dimensional images. LV mass was calculated by the formula of Devereux and normalized to body surface area7 in men and women. Age is expressed as mean ⫾ SD. For all other variables, frequency distributions are reported. Differences between subgroups and multiple-test analysis were assessed using Kruskal-Wallis analysis. A 2-tailed p value ⬍0.05 was considered evidence of statistical significance. Statistical analysis was performed using Program 3S (BMPD Software, Los Angeles, California). Athletes were arbitrarily divided into 4 groups according to the frequency and complexity of ventricular tachyarrhythmias during 24-hour Holter monitoring (Table 1) as follows: (1) no premature ventricular complexes (PVCs; n ⫽ 40): without PVCs, multiform PVCs, couplets, or nonsustained ventricular tachycardia (NSVT); (2) 1 to 100 PVCs (n ⫽ 71): a mean of 21 ⫾ 27 PVCs in 24 hours (5 also had multiform PVCs, 5 had couplets, and 4 had NSVT); (3) 101 to 1,000 PVCs (n ⫽ 33): a mean of 364 ⫾ 254 PVCs in 24 hours (8 also had multiform PVCs, 9 had couplets, and 2 had NSVT); and (4) ⬎1,000 PVCs (n ⫽ 31): a mean of 4,390 ⫾ 4,116 PVCs in 24 hours (range 1,060 to 20,579) (10 also had multiform PVCs, 9 had couplets, and 2 had NSVT).
athletes (14%), 16 men and 9 women, had LV hypertrophy, defined as an LV mass index ⱖ134 g/m2 in men and ⱖ110 g/m2 in women.7 No statistically significant differences were evident between LV mass (or mass index) and the grade or frequency of ventricular tachyarrhythmias (Table 1). Athletes with more frequent ventricular arrhythmias did not show parallel increases in LV mass, and athletes with the greatest LV mass did not demonstrate more frequent ventricular arrhythmias than athletes with lesser or normal mass. Of note, athletes with the most frequent and complex ventricular ectopy (those with ⬎1,000 PVCs) showed the lowest calculated LV masses and mass indexes, although this relation did not achieve statistical significance (Figure 1). Athletes with and without LV hypertrophy did not differ with respect to the total number of PVCs (p ⫽ 0.58), couplets (p ⫽ 0.63), and NSVT (p ⫽ 0.61). Furthermore, athletes with only uniform and isolated PVCs (n ⫽ 130) and those also with complex forms of ectopy (multiform PVCs, couplets, or runs of NSVT; n ⫽ 45) showed no statistical difference in LV mass index (97.9 ⫾ 21 vs 102.9 ⫾ 22 g/m2, p ⫽ 0.2). No relation was evident between sinus bradycardia at rest (⬍60 beats/min) and arrhythmia frequency (r ⫽ 0.22) in the overall study group, as well as the 4 subgroups with different frequencies of PVCs in 24 hours (no PVCs: 49 ⫾ 5 beats/min; 1 to 100 PVCs: 47 ⫾ 5 beats/min; 101 to 1,000 PVCs: 50 ⫾ 7 beats/min; ⬎1,000 PVCs: 49 ⫾ 5.1 beats/ min; p ⫽ 0.64). Discussion
Results Ventricular septal and LV posterior wall thicknesses were 9.4 ⫾ 1.3 mm (range 7 to 13) and 9.2 ⫾ 1.2 mm (range 7 to 13), respectively; 10 athletes (6%) had maximum LV wall thickness of 13 mm. The mean LV end-diastolic diameter was 53.6 ⫾ 5 (range 43 to 66), the mean LV mass was 195 ⫾ 56 g (range 93 to 388), and the mean LV mass index was 98.7 ⫾ 21 g/m2 (range 52 to 156). Twenty-five
Previously, we have shown that in elite athletes, frequent and complex ventricular ectopy documented by 24-hour ambulatory (Holter) electrocardiographic monitoring is not uncommon.4,5 In the present study, we found that ventricular tachyarrhythmias identified in elite athletes without cardiovascular abnormalities are largely unrelated to the presence or magnitude of training-induced LV hypertrophy. Indeed, paradoxically, those athletes with the highest fre-
1794
The American Journal of Cardiology (www.AJConline.org)
Figure 1. Relation between the frequency of ventricular tachyarrhythmias on 24-hour Holter electrocardiographic monitoring and LV mass index in 175 elite athletes without cardiovascular disease.
quency of ventricular arrhythmias during Holter monitoring showed a trend toward lower calculated LV mass and mass index. Furthermore, those athletes with LV hypertrophy showed ventricular arrhythmias less frequently than athletes without hypertrophy. These observations show that ventricular tachyarrhythmias in trained athletes (without cardiovascular abnormalities) arise largely independent of training-related LV remodeling and are also consistent with our previous observation that athletes experience similar LV remodeling, whether or not ventricular arrhythmias are reversed by deconditioning.8 This circumstance differs from that in pathologic forms of LV hypertrophy (such as in hypertrophic cardiomyopathy),9 in which greater LV mass and ventricular tachyarrhythmias are linked.10,11 Therefore, our data appear to dispute the suggestion that cellular electrophysiologic changes induced by cardiac hypertrophy in trained athletes account for many of the abnormalities on athletes’ electrocardiograms, including high-grade ventricular ectopy, or sudden cardiac death.12 Given the finding that LV hypertrophy and remodeling do not represent the substrate for the ventricular tachyarrhythmias that not infrequently occur in elite athletes without cardiovascular disease, the underlying determinants of this ectopy remain unresolved. However, other potential causes include specific autonomic nervous system alterations induced by training and bradycardia-dependent ectopy.13 Intensive physical training has been reported to shift cardiovascular autonomic modulation from parasympathetic toward sympathetic dominance, thereby enhancing cardiovascular performance at peak training.14 The predominance of sympathetic tone could be responsible for increased ventricular irritability and explain the clinical occurrence of ventricular arrhythmias in some athletes.15 In this regard, we have previously proposed that autonomic dysfunction is a possible mechanism by which ventricular tachyarrhythmias in elite athletes were diminished or abolished with deconditioning.8 Also, sinus bradycardia, which is a common finding in elite athletes, did not show any relation to arrhythmia frequency, excluding the possibility that a bra-
dycardia-dependent phenomenon explained the genesis of ventricular tachyarrhythmias in our elite athletes. Finally, it should be noted that the magnitude of traininginduced LV hypertrophy in this cohort of elite athletes was relatively mild. Only about 15% of our athletes were defined as having LV hypertrophy on the basis of an LV mass index ⱖ134 g/m2 in men and ⱖ110 g/m2 in women. Nevertheless, this proportion is consistent with that previously reported in other populations of highly trained athletes.16 –18 Athletes identified as having structural heart disease (including those with pathologic forms of LV hypertrophy such as hypertrophic cardiomyopathy) were previously excluded from sports participation, and this may also help to explain the mild degree of exercise-induced hypertrophy documented in this cohort of elite Italian athletes.19,20 In conclusion, ventricular ectopy in elite athletes is unrelated to the magnitude of training-induced LV hypertrophy. These data further underscore the benign nature of ventricular tachyarrhythmias in highly trained athletes without cardiovascular abnormalities. 1. Huston P, Puffer JC, MacMillan RW. The athletic heart syndrome. N Engl J Med 1985;315:24 –32. 2. Maron BJ, Pelliccia A. The heart of trained athletes: cardiac remodeling and the risks of sports, including sudden death. Circulation 2006;114:1633–1644. 3. Maron BJ, Pelliccia A, Spataro A, Granata M. Reduction in left ventricular wall thickness after deconditioning in highly trained Olympic athletes. Br Heart J 1993;69:125–128. 4. Biffi A, Pelliccia A, Verdile L, Fernando F, Spataro A, Caselli S, Santini M, Maron BJ. Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes. J Am Coll Cardiol 2002;40:446 – 452. 5. Italian Society of Sports Cardiology. Standards of dynamic electrocardiography (Holter) in top-ranking athletes of different sports. In: Lubich T, Venerando A, Zeppilli P, eds. Sports Cardiology. 2nd ed. Bologna, Italy: Aulo Gaggi, 1989:355–361. 6. Striegel H, Rossner D, Simon P, Niess AM. The World Anti-Doping Code 2003: consequences for physicians associated with elite athletes. Int J Sports Med 2005;29:1–14. 7. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertro-
Miscellaneous/Athlete’s Heart and Ventricular Arrhythmias
8.
9. 10. 11. 12. 13.
14.
phy: comparison with necropsy findings. Am J Cardiol 1986;57:450 – 458. Biffi A, Maron BJ, Verdile L, Fernando F, Spataro A, Marcello G, Ciardo R, Ammirati A, Colivicchi F, Pelliccia A. Impact of deconditioning on ventricular tachyarrhythmias in trained athletes. J Am Coll Cardiol 2004;44:1053–1058. Adabag AS, Maron BJ. Implication of arrhythmias and prevention of sudden death in hypertrophic cardiomyopathy. Ann Noninvasive Electrocardiol 2007;12:171–180. Spirito P, Watson RM, Maron BJ. Relation between extent of left ventricular hypertrophy and occurrence of ventricular tachycardia in hypertrophic cardiomyopathy. Am J Cardiol 1987;60:1137–1142. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk for sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342:1778 –1785. Hart G. Exercise-induced cardiac hypertrophy: a substrate for sudden death in athletes? Exp Physiol 2003;88:639 – 644. Sapoznikov D, Luria MH, Gotsman MS. Changes in sinus RR interval patterns preceding ventricular ectopic beats: assessment in rate enhancement and dynamic heart rate trends. Int J Cardiol 1999;69:217– 224. Iellamo F, Legramante JM, Pigozzi F, Spataro A, Norbiato G, Lucini D, Pagani M. Conversion from vagal to sympathetic predominance
15.
16.
17.
18. 19.
20.
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with strenuous training in high performance world-class athletes. Circulation 2002;105:2719 –2724. Chen LS, Zhou S, Fishbein MC, Chen PS. New perspectives on the role of autonomic nervous system in the genesis of arrhythmias. J Cardiovasc Electrophysiol 2007;18:123–127. Pelliccia A, Maron BJ, Spataro A, Proschan MA, Spirito P. The upper limit of physiologic cardiac hypertrophy in highly trained elite athletes. N Engl J Med 1991;324;295–301. Pelliccia A, Maron BJ, Culasso F, Spataro A, Caselli G. Athlete’s heart in women. Echocardiographic characterization of highly trained elite female athletes. JAMA 1996;276:211–215. Pelliccia A, Culasso F, Di Paolo FM, Maron BJ. Physiologic left ventricular cavity dilatation in elite athletes. Ann Intern Med 1999;130:23–31. Corrado D, Basso C, Pavei A, Michieli P, Schiavon M, Thiene G. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. JAMA 2006;296:1593–1601. Pelliccia A, Di Paolo FM, Corrado D, Buccolieri C, Quattrini FM, Pisicchio C, Spataro A, Biffi A, Granata M, Maron BJ. Evidence for efficacy of the Italian national pre-participation screening programme for identification of hypertrophic cardiomyopathy in competitive athletes. Eur Heart J 2006;27:2196 –2200.
a Institute of Sports Medicine and Science, Italian Olympic Committee, Rome, Italy; bHypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota; and cUniversity of Rome “La Sapienza,” Department of Statistics, Rome, Italy. Manuscript received October 9, 2007; revised manuscript received and accepted February 10, 2008. *Corresponding author: Tel: 39-06-3685-9185; fax 39-06-4746050. E-mail address: [email protected] (A. Biffi).
0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2008.02.081
Methods From May 2005 to February 2006, 738 athletes were examined at the Institute of Sports Medicine and Science in Rome, a national center for the evaluation of elite Italian athletes. Of the 738 athletes, 175 were selected for the study group on the basis of the absence of cardiovascular abnormalities and/or symptoms and elite levels of training and competition (Olympic or world-class athletes). Cardiovascular evaluation was performed during periods of peak training. Each athlete was studied during a 24-hour period of ambulatory (Holter) electrocardiographic monitoring, which included a conditioning session (an average of 1 hour in duration), consistent with that usually performed by the athlete. The remaining time was occupied by usual daily activities, which could include noncompetitive and recreational physical activities. No athlete was taking antiarrhythmic or other cardioactive medications. All athletes underwent routine screening for performance-enhancing drugs in accord with the World Anti-Doping Agency list6 of the International Olympic Committee (including steroids, amphetamines, cocaine, growth hormone, and erythropoietin), with negative results. The mean age of the athletes was 23 ⫾ 6 years (range 15 to 43), and 108 (62%) were male. Subjects were engaged in 35 sports, most commonly rowing (n ⫽ 24 [14%]), track and field (n ⫽ 20 [11%]), and swimming (n ⫽ 16 [9%]). Echocardiographic studies were performed using a Hewlett-Packard 77020 AC (Hewlett-Packard Corporation, Palo Alto, California) or a Sonos 5500 (Philips Medical Systems, Andover, Massachusetts). Images of the heart www.AJConline.org
Miscellaneous/Athlete’s Heart and Ventricular Arrhythmias
1793
Table 1 Demographic, clinical, and echocardiographic data from 175 elite athletes with ambulatory Holter electrocardiograms Variable
Age (yrs) Men/women Heart rate at rest (beats/min) PVCs Couplets NSVT Ventricular septum (mm) Posterior wall thickness (mm) LV end diastolic diameter (mm) LV mass (g) LV mass index (g/m2)
Total (n ⫽ 175)
23.6 ⫾ 6 108/67 48.8 ⫾ 6 802 ⫾ 2,308 23 (13%) 8 (5%) 9.4 ⫾ 1.3 9.2 ⫾ 1.2 53.6 ⫾ 5 92 ⫾ 57 99 ⫾ 21
PVCs
p Value
Group A 0 (n ⫽ 40)
Group B 1–100 (n ⫽ 71)
Group C 101–1,000 (n ⫽ 33)
Group D ⬎1,000 (n ⫽ 31)
23.4 ⫾ 5.4 23/17 49.3 ⫾ 5.5 0 0 0 9.4 ⫾ 1.4 9.3 ⫾ 1.3 52.9 ⫾ 4.1 188 ⫾ 56 98.5 ⫾ 21
24.1 ⫾ 6.1 42/29 47.4 ⫾ 5.4 21 ⫾ 27 5 (7%) 4 (5%) 9.4 ⫾ 1.7 9.4 ⫾ 1.3 53.7 ⫾ 5.7 195 ⫾ 66 100 ⫾ 24
23.8 ⫾ 6 21/12 49.6 ⫾ 7 364 ⫾ 254 9 (28%) 2 (6%) 9.5 ⫾ 1 9.2 ⫾ 1.1 53.6 ⫾ 5.3 191 ⫾ 19 99 ⫾ 19
23.1 ⫾ 5.5 22/9 48.6 ⫾ 5.1 4.390 ⫾ 4.116 9 (30%) 2 (7%) 9.3 ⫾ 1.1 8.93 ⫾ 1 54.5 ⫾ 3.9 188 ⫾ 43 98 ⫾ 19
0.41 0.01* 0.62 0.001 0.01† 0.89 0.11 0.10 0.12 0.59 0.62
Data are expressed as mean ⫾ SD or as number (percentage). * Groups A and B versus group D. † Groups C and D versus groups A and B.
were obtained in multiple cross-sectional planes using standard transducer positions. LV cavity dimensions, anterior ventricular septal and posterior free wall thicknesses, and left atrial dimensions were obtained from M-mode echocardiograms. To enhance the accuracy of LV wall thickness measurements, these dimensions were verified from the 2-dimensional images. LV mass was calculated by the formula of Devereux and normalized to body surface area7 in men and women. Age is expressed as mean ⫾ SD. For all other variables, frequency distributions are reported. Differences between subgroups and multiple-test analysis were assessed using Kruskal-Wallis analysis. A 2-tailed p value ⬍0.05 was considered evidence of statistical significance. Statistical analysis was performed using Program 3S (BMPD Software, Los Angeles, California). Athletes were arbitrarily divided into 4 groups according to the frequency and complexity of ventricular tachyarrhythmias during 24-hour Holter monitoring (Table 1) as follows: (1) no premature ventricular complexes (PVCs; n ⫽ 40): without PVCs, multiform PVCs, couplets, or nonsustained ventricular tachycardia (NSVT); (2) 1 to 100 PVCs (n ⫽ 71): a mean of 21 ⫾ 27 PVCs in 24 hours (5 also had multiform PVCs, 5 had couplets, and 4 had NSVT); (3) 101 to 1,000 PVCs (n ⫽ 33): a mean of 364 ⫾ 254 PVCs in 24 hours (8 also had multiform PVCs, 9 had couplets, and 2 had NSVT); and (4) ⬎1,000 PVCs (n ⫽ 31): a mean of 4,390 ⫾ 4,116 PVCs in 24 hours (range 1,060 to 20,579) (10 also had multiform PVCs, 9 had couplets, and 2 had NSVT).
athletes (14%), 16 men and 9 women, had LV hypertrophy, defined as an LV mass index ⱖ134 g/m2 in men and ⱖ110 g/m2 in women.7 No statistically significant differences were evident between LV mass (or mass index) and the grade or frequency of ventricular tachyarrhythmias (Table 1). Athletes with more frequent ventricular arrhythmias did not show parallel increases in LV mass, and athletes with the greatest LV mass did not demonstrate more frequent ventricular arrhythmias than athletes with lesser or normal mass. Of note, athletes with the most frequent and complex ventricular ectopy (those with ⬎1,000 PVCs) showed the lowest calculated LV masses and mass indexes, although this relation did not achieve statistical significance (Figure 1). Athletes with and without LV hypertrophy did not differ with respect to the total number of PVCs (p ⫽ 0.58), couplets (p ⫽ 0.63), and NSVT (p ⫽ 0.61). Furthermore, athletes with only uniform and isolated PVCs (n ⫽ 130) and those also with complex forms of ectopy (multiform PVCs, couplets, or runs of NSVT; n ⫽ 45) showed no statistical difference in LV mass index (97.9 ⫾ 21 vs 102.9 ⫾ 22 g/m2, p ⫽ 0.2). No relation was evident between sinus bradycardia at rest (⬍60 beats/min) and arrhythmia frequency (r ⫽ 0.22) in the overall study group, as well as the 4 subgroups with different frequencies of PVCs in 24 hours (no PVCs: 49 ⫾ 5 beats/min; 1 to 100 PVCs: 47 ⫾ 5 beats/min; 101 to 1,000 PVCs: 50 ⫾ 7 beats/min; ⬎1,000 PVCs: 49 ⫾ 5.1 beats/ min; p ⫽ 0.64). Discussion
Results Ventricular septal and LV posterior wall thicknesses were 9.4 ⫾ 1.3 mm (range 7 to 13) and 9.2 ⫾ 1.2 mm (range 7 to 13), respectively; 10 athletes (6%) had maximum LV wall thickness of 13 mm. The mean LV end-diastolic diameter was 53.6 ⫾ 5 (range 43 to 66), the mean LV mass was 195 ⫾ 56 g (range 93 to 388), and the mean LV mass index was 98.7 ⫾ 21 g/m2 (range 52 to 156). Twenty-five
Previously, we have shown that in elite athletes, frequent and complex ventricular ectopy documented by 24-hour ambulatory (Holter) electrocardiographic monitoring is not uncommon.4,5 In the present study, we found that ventricular tachyarrhythmias identified in elite athletes without cardiovascular abnormalities are largely unrelated to the presence or magnitude of training-induced LV hypertrophy. Indeed, paradoxically, those athletes with the highest fre-
1794
The American Journal of Cardiology (www.AJConline.org)
Figure 1. Relation between the frequency of ventricular tachyarrhythmias on 24-hour Holter electrocardiographic monitoring and LV mass index in 175 elite athletes without cardiovascular disease.
quency of ventricular arrhythmias during Holter monitoring showed a trend toward lower calculated LV mass and mass index. Furthermore, those athletes with LV hypertrophy showed ventricular arrhythmias less frequently than athletes without hypertrophy. These observations show that ventricular tachyarrhythmias in trained athletes (without cardiovascular abnormalities) arise largely independent of training-related LV remodeling and are also consistent with our previous observation that athletes experience similar LV remodeling, whether or not ventricular arrhythmias are reversed by deconditioning.8 This circumstance differs from that in pathologic forms of LV hypertrophy (such as in hypertrophic cardiomyopathy),9 in which greater LV mass and ventricular tachyarrhythmias are linked.10,11 Therefore, our data appear to dispute the suggestion that cellular electrophysiologic changes induced by cardiac hypertrophy in trained athletes account for many of the abnormalities on athletes’ electrocardiograms, including high-grade ventricular ectopy, or sudden cardiac death.12 Given the finding that LV hypertrophy and remodeling do not represent the substrate for the ventricular tachyarrhythmias that not infrequently occur in elite athletes without cardiovascular disease, the underlying determinants of this ectopy remain unresolved. However, other potential causes include specific autonomic nervous system alterations induced by training and bradycardia-dependent ectopy.13 Intensive physical training has been reported to shift cardiovascular autonomic modulation from parasympathetic toward sympathetic dominance, thereby enhancing cardiovascular performance at peak training.14 The predominance of sympathetic tone could be responsible for increased ventricular irritability and explain the clinical occurrence of ventricular arrhythmias in some athletes.15 In this regard, we have previously proposed that autonomic dysfunction is a possible mechanism by which ventricular tachyarrhythmias in elite athletes were diminished or abolished with deconditioning.8 Also, sinus bradycardia, which is a common finding in elite athletes, did not show any relation to arrhythmia frequency, excluding the possibility that a bra-
dycardia-dependent phenomenon explained the genesis of ventricular tachyarrhythmias in our elite athletes. Finally, it should be noted that the magnitude of traininginduced LV hypertrophy in this cohort of elite athletes was relatively mild. Only about 15% of our athletes were defined as having LV hypertrophy on the basis of an LV mass index ⱖ134 g/m2 in men and ⱖ110 g/m2 in women. Nevertheless, this proportion is consistent with that previously reported in other populations of highly trained athletes.16 –18 Athletes identified as having structural heart disease (including those with pathologic forms of LV hypertrophy such as hypertrophic cardiomyopathy) were previously excluded from sports participation, and this may also help to explain the mild degree of exercise-induced hypertrophy documented in this cohort of elite Italian athletes.19,20 In conclusion, ventricular ectopy in elite athletes is unrelated to the magnitude of training-induced LV hypertrophy. These data further underscore the benign nature of ventricular tachyarrhythmias in highly trained athletes without cardiovascular abnormalities. 1. Huston P, Puffer JC, MacMillan RW. The athletic heart syndrome. N Engl J Med 1985;315:24 –32. 2. Maron BJ, Pelliccia A. The heart of trained athletes: cardiac remodeling and the risks of sports, including sudden death. Circulation 2006;114:1633–1644. 3. Maron BJ, Pelliccia A, Spataro A, Granata M. Reduction in left ventricular wall thickness after deconditioning in highly trained Olympic athletes. Br Heart J 1993;69:125–128. 4. Biffi A, Pelliccia A, Verdile L, Fernando F, Spataro A, Caselli S, Santini M, Maron BJ. Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes. J Am Coll Cardiol 2002;40:446 – 452. 5. Italian Society of Sports Cardiology. Standards of dynamic electrocardiography (Holter) in top-ranking athletes of different sports. In: Lubich T, Venerando A, Zeppilli P, eds. Sports Cardiology. 2nd ed. Bologna, Italy: Aulo Gaggi, 1989:355–361. 6. Striegel H, Rossner D, Simon P, Niess AM. The World Anti-Doping Code 2003: consequences for physicians associated with elite athletes. Int J Sports Med 2005;29:1–14. 7. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertro-
Miscellaneous/Athlete’s Heart and Ventricular Arrhythmias
8.
9. 10. 11. 12. 13.
14.
phy: comparison with necropsy findings. Am J Cardiol 1986;57:450 – 458. Biffi A, Maron BJ, Verdile L, Fernando F, Spataro A, Marcello G, Ciardo R, Ammirati A, Colivicchi F, Pelliccia A. Impact of deconditioning on ventricular tachyarrhythmias in trained athletes. J Am Coll Cardiol 2004;44:1053–1058. Adabag AS, Maron BJ. Implication of arrhythmias and prevention of sudden death in hypertrophic cardiomyopathy. Ann Noninvasive Electrocardiol 2007;12:171–180. Spirito P, Watson RM, Maron BJ. Relation between extent of left ventricular hypertrophy and occurrence of ventricular tachycardia in hypertrophic cardiomyopathy. Am J Cardiol 1987;60:1137–1142. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk for sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342:1778 –1785. Hart G. Exercise-induced cardiac hypertrophy: a substrate for sudden death in athletes? Exp Physiol 2003;88:639 – 644. Sapoznikov D, Luria MH, Gotsman MS. Changes in sinus RR interval patterns preceding ventricular ectopic beats: assessment in rate enhancement and dynamic heart rate trends. Int J Cardiol 1999;69:217– 224. Iellamo F, Legramante JM, Pigozzi F, Spataro A, Norbiato G, Lucini D, Pagani M. Conversion from vagal to sympathetic predominance
15.
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