Article

Sudden death in competitive athletes: does a circadian variation in occurrence exist?

05:59 PM; and evening, 06:00-11:59 PM). Group A was analyzed applying partial Fourier series, by means of a chronobiologic software that selects the harmonic(s) best explaining the variance of the data [14]. The percentage of rhythm (PR: percentage of the overall variability of data about the arithmetic mean) and the F test statistic are used to test the hypothesis of zero amplitude null hypothesis (absence of periodicity). The software also calculates the acrophase (peak) of each single harmonic and the peak and trough times of the overall best fitted curve. Significance was assumed for P b .05. Group B was analyzed by means of ?2 test goodness of fit [15].

Thirty-seven athletes with SD were included in group A (Table), and a total of 63 were included in group B (age, 18-37 years; mean, 26.6 +- 4.8 years). As for group A, chronobiologic analysis yielded a significant Circadian variation, characterized by a bimodal frequency peak. The main circadian peak (periodicity, 24 hours; PR, 52.5%; P b .001) was registered at 04:58 PM (95% confidence limits [CL], 15:32-18:24 PM), and a smaller accessory peak (periodicity, 12 hours; PR, 14.7%; P =

.029) was found at 08:29 AM/PM (96% CL, 06:34-09:18).

Overall, the circadian rhythm (peak at 07:00 PM, trough at 2:56 AM) was highly significant (PR, 67.3%; P b

.001) (Fig. 1). For group B, ?2 test showed a statistically significant difference (?2, 10.0; P = .024), with highest frequency of cases in the evening (n = 25, 39.7%) and lowest during night time (n = 7, 11.1%) (Fig. 2).

This preliminary study shows that also in athletes, SD exhibits a circadian pattern of onset, characterized by 2 frequency peaks. Muller et al [6] first revealed a prominent circadian morning incidence of SCD, with low nocturnal incidence [6], remarkably similar to that reported for nonfatal MI [4]. After adjustment for individual wake time, the onset of events was higher during the first 3 hours after awakening [16]. A same pattern was confirmed also for cardiac arrests [17-19], and further studies revealed the existence of a second peak in the afternoon-evening hours, maybe attri- butable to arrhythmias. Arrhythmic events exhibit circadian rhythm, also in apparently healthy subjects [20]. Arntz et al

[21] reported a marked circadian variation in the occurrence of SD with a primary morning peak and a secondary afternoon peak. The subgroup of patients with ventricular

Athlete

Age

Hour

Sport discipline

Date

Country

1

24

5:45

PM

Soccer

05/10/2000

Romania

2

24

11:50

AM

Boxing

25/10/2000

USA

3

33

2:37

PM

Baseball

02/06/2002

USA

4

28

7:41

PM

Soccer

26/06/2003

Cameroon

5

24

10:30

PM

Soccer

25/01/2004

Hungary

6

30

10:14

PM

Soccer

27/10/2004

Brasil

7

24

9:00

AM

Soccer

28/11/2004

Argentina

8

28

3:30

PM

Soccer

12/04/2005

UK

9

37

4:15

PM

Cycling

15/06/2005

Italy

10

25

9:15

PM

Boxing

01/04/2007

Philippines

11

22

8:30

PM

Soccer

25/08/2007

Spain

12

28

8:46

AM

Marathon

03/11/2007

USA

13

35

5:18

PM

Soccer

29/12/2007

UK

14

27

0:00

AM

Cycling

11/03/2008

Portugal

15

24

11:51

AM

Soccer

03/04/2008

Croatia

16

33

9:00

PM

Soccer

07/07/2008

Romania

17

19

5:03

PM

Hockey

13/10/2008

Russia

18

21

5:30

PM

Cycling

05/02/2009

Belgium

19

36

9:30

AM

Marathon

20/08/2009

USA

20

26

10:30

AM

Marathon

20/08/2009

USA

21

19

11:30

PM

Soccer

22/10/2009

Italy

22

24

5:10

PM

Basketball

26/10/2009

Portugal

23

25

12:13

PM

Soccer

15/11/2009

Italy

24

31

3:30

AM

Soccer

16/11/2009

Mexico

25

26

7:20

PM

Hockey

08/12/2009

Sweden

26

26

8:21

AM

Football

17/01/2010

USA

27

25

8:53

PM

Soccer

06/03/2010

Nigeria

28

32

6:05

PM

Soccer

06/05/2010

Croatia

29

26

7:00

PM

Soccer

08/05/2010

Brasil

30

31

1:15

PM

Soccer

27/10/2010

Spain

31

23

10:45

PM

Football

27/04/2011

USA

32

34

1:06

PM

Soccer

04/08/2011

Japan

33

30

4:10

PM

Soccer

13/11/2011

Belgium

34

27

2:43

PM

Soccer

15/03/2012

India

35

23

7:11

PM

Soccer

17/03/2012

UK

36

20

3:50

PM

Soccer

18/03/2012

Italy

37

37

10:00

PM

Volleyball

24/03/2012

Italy

fibrillation as initially documented arrhythmia showed a

Table Cases of sudden death of competitive athletes with precise time of death

similar circadian variation, whereas patients with asystole or 5

pulseless bradyarrhythmias were more evenly distributed

during the daytime. Moreover, patients older than 65 years 4

had a monophasic distribution, whereas younger patients

had morning and afternoon peaks. Two peaks, approxi- 3

mately of the same size (8-11 AM, 4-7 PM) were confirmed

N

in a large cohort, out-of-hospital cardiac arrests [22]. The 2

evening peak was attributed primarily to the patients found

in ventricular fibrillation, whereas arrests with other 1

arrhythmias exhibited mainly a morning peak. Because

previous studies could be exposed to the selection bias 0

of excluding nocturnal unwitnessed deaths, Tofter et al

TIME (hours)

[23] studied patients with implanted cardioverter/defibrilla- tor and confirmed that a higher proportion of Ventricular tachyarrhythmias began in the late morning. Again, Behrens

Fig. 1 circadian distribution of cases of sudden death in competitive athletes during competition with precise (+- 30 minutes) time of death (n = 37). Superimposed is the best fitting curve.

20

18

16

14

12

10

N

8

6

4

2

0

NIGHT

MORNING

AFTERNOON EVENING

Anna Maria Malagoni MD, PhD

Fabio Manfredini, MD Vascular Diseases Center University of Ferrara

Italy E-mail addresses: [email protected]

[email protected]

Roberto Manfredini MD

Clinica Medica University of Ferrara

Italy E-mail address: [email protected]

Fig. 2 Circadian distribution of cases of sudden death in

competitive athletes during competition with both precise and

probable (within 6-hour period) time of death (n = 63).

et al [24] found that shock episodes terminating potentially life-threatening ventricular tachyarrythmias exhibited a primary morning peak and a secondary one, much smaller, between 4 and 8 PM. Regular exercise reduces the incidence of CHD and MI [25], but vigorous activity may enhance the risk of MI and SD among patients with occult or overt CHD [26,27]. Although with the limitations of small sample size and the possible conditioning effect of competition time schedule, it is interesting that the circadian pattern of SD onset in athletes resembles that of common people, with evening and morning peaks. It is possible that, in addition to vigorous exercise during competition, temporally related physiologic changes deter- mining electrical myocardial vulnerability may also play a triggering role. Further studies on larger databases will test these preliminary data and provide useful insights for prevention.

Alfredo De Giorgi MD

Clinica Medica University of Ferrara

Italy E-mail address: [email protected]

Federica Achilli La Nuova Ferrara Ferrara, Italy

E-mail address: [email protected]

Fabio Fabbian MD Marco Pala MD

Alessandra Mallozzi Menegatti

Clinica Medica University of Ferrara

Italy E-mail addresses: [email protected]

[email protected] [email protected]

doi:10.1016/j.ajem.2012.04.027

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