I have financial relationships to disclose Consultant for: st Jude, Boston, Sorin, Biotronik, Medtronic, Sanofi, Merck,

Menarin Research support from: st Jude, Boston, Sorin, Biotronik, Medtronic, Sanofi,

Merck, Menarin

Atrial Fibrillation and Sports.

Hospital Clinic. Universitat de Barcelona

• 1777 competitive athletes without heart disease

• Mean age 24± 6 years

• Mean age at most recent assessment 33±6

• mean time of sports involvement 6 years

• 61 % continued with the training during FU

Pellicia et al. JACC 2005

Pellicia et al. JACC 2005

In the thirties < 0.5%

Pellicia et al. JACC 2005

Lone atrial fibrillation in Marathon runners

Hospital Clinic. Thorax Institute. University of Barcelona,

Hospital del Mar. Autonomous University of Barcelona

Institut Municipal Investigacions Mèdiques IMIM. Barcelona.

Molina et al. Europace 2008

• 270 healthy men that ran the marathon in

Barcelona in 1993.

• Control group: 305 healthy sedentary men <

300 Kcal/day of physical activity, recruited at

the REGICOR study

Methods

Molina et al. Europace 08

In the forties 9/183 (5%)

Lone atrial fibrillation in Marathon runners

Adjusted for age and systolic blood pressure

Grimsmo J. Eur J Cardiovasc Prev Rehabil 17:100–105 2010

In the sixties 15-18%

Athletes or vigorous exercise?

Is there a threshold?

• 16921 participants at the Physicians

Health Study

• Healthy individuals

• 12 years follow up

• 70 patients with lone AF younger than 65y.

• Regular sport practice 65% among patients with

AF and 15% in the general male population of

individuals younger than 65 in Catalonia

(REGICOR study)

Hospital Clínic. University of Barcelona. Institut Municipal d’Investigacions Mèdiques de Barcelona.

Int J Cardiol 2005

Logistic Regression Analysis

Vagal Atrial Fibrillation

Cases/Controls OR (95% CI) P

Sport Practice 17/71 3.03 (0.8-11.0) 0.09

Current Sport

Practice

6/15 3.13 (1.02-9.6) 0.046

Lifetime hours

100-1560 hours

3/29

1.3 (0.25-7)

NS

1561-5668 hours 7/19 4.67 (1.08-20) 0.039

Current practice

> 1500 hours (3

hours/week, 10

years

6/14 5.06 (1.35-19) 0.016

Is sports related lone AF a

familial disease?

Familial Atrial Fibrillation and

sports: hypothesis • “Dose related risk” of AF in sports goes

against a familial disease

• Genetic forms have a high penetrance and

does not need the “trigger effect of sport”

• Familial forms of AF are very uncommon

and a family history is rarely seen.

• Athletes show deep structural changes, that

may explain AF withouth the need of other

etiologic factors.

Genetic Predisposition or Genetic

Disease

• Atrial fibrillation as a monogenic disease

• Atrial firillation associated with other

monogenic diseases

• Genetic predispostion to acquired atrial

fibrillation

• Wolff L. N Engl J Med. 1943

• Gould WL Arch Int Med 1957

• Phair WB Canad Med Ass 1963

• Derrida JP et al Nouv Pres Med 1976

• Wen-tai Y Chin Med J 1983

• Ardiaca A et al Rev Esp Card 1987

ATRIAL FIBRILLATION AS A MONOGENIC

DISEASE

Historical Perspective

I:1 I:2

FAMILIAL ATRIAL FIBRILLATION

REGION SHARED ON 10q2

AFFECTED

NON AFFECTED

DEAD

Brugada R et al NEJM, 1997

• Mean Age of Diagnosis 18 years

• Range in Age of Diagnosis in utero-35 years

• Echocardiogram Normal

• Patients with Chronic AF 51/52

• Asymptomatic 36/52

• Heart rate 80-140 bpm

FAMILIAL ATRIAL FIBRILLATION

CLINICAL FEATURES

Brugada R et al NEJM, 1997

Chen YH, et al. Science 2003

Hong et al. JCE, 2005 Gussak et al. Cardiology 2000

Clinical Implications

• Each family appears to have its own gene

• No change in clinical approach

• Penetrance appears high

Date of download: 8/18/2012 Copyright © 2012 American Medical

Association. All rights reserved.

From: Association Between Familial Atrial Fibrillation and Risk of New-Onset Atrial Fibrillation

JAMA. 2010;304(20):2263-2269. doi:10.1001/jama.2010.1690

Date of download: 8/18/2012 Copyright © 2012 American Medical

Association. All rights reserved.

From: Association Between Familial Atrial Fibrillation and Risk of New-Onset Atrial Fibrillation

JAMA. 2010;304(20):2263-2269. doi:10.1001/jama.2010.1690

Physical activity, height and left atrial size are

independent risk factors for lone atrial fibrillation in

middle aged healthy individuals

- Thorax Institute. Hospital Clinic, University of Barcelona

- IMIM. Institut Municipal de Investigació Mèdica. Barcelona

Mont L, Tamborero D, Elosua R, Molina I, Collvinent B,

Sitges M, Vidal B, Scalise A, Tejeira A, Berruezo and

Brugada J on behalf of the GIRAFA (Grup Integrat de

Recerca en FA) investigators

Mont et al. Europace 2008

Methods

• Design: Prospective, case-control study

• Population:

– 107 consecutive patients younger 18 to 65

– Recent onset Lone AF, seen at the emergency

room (> 48 hours).

• Controls: 1:1 age and sex matched controls

Patients

N=107

Controls

N= 107

Age (years) 48.0±11.6 47.6±10.2

Male sex (%) 74 (69%) 74 (69%)

Smoking (%) 53 (50%) 53 (50%)

Paroxysmal/Persistent AF (%) 61 (57%) / 46 (43%) --

Vagal AF (%) 75 (70%) --

First AF episode/ recurrent AF 46 (43%) / 61(57%) --

Number of AF episodes 4.5±6.9 --

AF duration (hours) 15.4±13.7 --

Demographic characteristics

Adjusted Odds ratios and 95% IC of lone AF form heavy physical

activity, height and LA AP diameter

Odds ratio

(95% confidence

interval)

P value

Cumulated intense physical activity

0 hours 1

1-563 hours 1.77 (0.22-14.26) 0.5900

564 -> hours 7.31 (2.33-22.96) 0.0006

Height

155- 1

165- 15.47 (2.23-107) 0.0056

177- 17.00 (1.51-192) 0.0220

Left atrial anteroposterior

diameter (mm) 1.51 (1.25-1.83)

0.0002

Sustained Endurance Training Creates a

Substrate for Atrial Fibrillation in Rats

Hospital Clínic. University of Barcelona

Montreal Heart Institute

Sophie Cardin

Yanfen Shi

Patrick Lawler

Ange Maguy

Jean-Claude Tardif

Nathalie L’Heureux

Chantal St-Cyr

Audrey Bonard

Stanley Nattel

Begoña Benito

Gemma Gay

Eduard Guasch

Valeria Sirenko

David Tamborero

Anna Serrano

Lluis Mont

Benito et al. Circulation 2011

Training Protocol

4 weeks

8 weeks

16 weeks

Rest for 3 days

Sacrifice

Echocardiographic data after 16

weeks of training

sedentary exercise

IVS thickness (cm)

3.0 ± 0.0 3.6 ± 0.1 ***

LV diameter (cm)

14.3 ± 0.3 16.4 ± 0.3 ***

LV mass (g) 18.1 ± 0.4 21.5 ± 0.7 ***

LA diam (SYST)

9.2 ± 0.2 11.5 ± 0.3 ***

LA diam (DIAST)

6.4 ± 0.2 7.6 ± 0.2 *

Adjusted for BSA

ECG parameters

16 weeks

CTL (n=18) Ex (n=17)

HR (bpm) 346 ± 9 312 ± 11 **

PR interval (ms) 56.4 ± 1.4 60.9 ± 1.8

QRS duration (ms) 23.1 ± 0.3 23.9 ± 0.4

QTc interval (ms) (Bazett’s)

224 ± 4 228 ± 4

EPS parameters

CTL (n=15) Ex (n=14)

EP parameters

Sinus cycle length

(ms) 199.1 ± 4.0 222.9 ± 5.8 **

SN recovery time (ms) 238.9 ± 7.4 252.4 ± 7.1

Anterograde Wenck

(ms) 123.4 ± 2.6 138.5 ± 4.5 **

Atrial refractory period

(ms) 42.9 ± 1.4 40.2 ± 1.0

Inducible arrhythmias

* Mean duration: 8.7 ± 2.0 min

• Protein expression of fibrotic markers in atria:

Mean ± SEM;* p<0.05 (n CTL=6, n Ex=8)

Atrial fibrosis

Ex

CTL

RA LA

Mean ± SEM. * p<0.05; ** p<0.01; *** p<0.001

Chronic high-level exercise

• Hemodynamic effects:

Atrial overload

Atrial enlargement

Atrial fibrosis

ATRIAL FIBRILLATION

• Increased vagal tone

Summary of mechanisms

Summary

• AF related to sports seems to be the

consequence of atrial remodelling and

increased vagal tone.

• Monogenic AF seems to be a high

penetrance and not particularly linked to

sport practice

• A genetic predisposition may be present in

certain individuals.