DECLARATION OF CONFLICT OF INTEREST. None

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1 DECLARATION OF CONFLICT OF INTEREST None

2 Controversies on marathon and beyond: Elevated biomarkers as a proof of cardiac damage: Contra Jürgen Scharhag, FACSM, FESC Internal Medicine III: Cardiology, Angiology and Pneumology Head: Prof. H. Katus University Clinic Heidelberg Germany

3 Neilan et al. Circulation 2006;114: Marathon and cardiac biomarkers Editorial Marathoner`s Heart? Paul D. Thompson, Fred S. Apple, Alan Wu Circulation 2006;114: decrease in LV diastolic function decrease in RV contractility increase in PASP (20 vs. 41 mmhg) and mpap (12 vs. 25 mmhg) relations between cardiac biomarkers and some parameters of cardiac function (E lat and A lat vs. NT-proBNP; mpap vs. ctnt)

4 Marathon Run 100 km Run MTB-Marathon 2,0 2,0 2,0 1,8 1,8 1,8 1,6 1,6 1,6 1,4 1,4 1,4 Troponin I [µg/l] 1,2 1,0 0,8 0,6 Troponin I [µg/l] 1,2 1,0 0,8 0,6 Troponin I [µg/l] 1,2 1,0 0,8 0,6 0,4 0,4 0,4 0,2 0,2 0,2 Troponin T [µg/l] 0,0 0,60 0,55 0,50 0,45 0,40 0,35 0,30 0,25 0,20 0,15 0,10 0,05 0,00 0,0 0,0 Before < 15 min post 3 h post 1 d post Before < 15 min post 3 h post Before < 15 min post 3 h post 1 d post 0,60 0,60 TnI > 0,04 ng/ml 74 % 0,55 0,55 0,50 0,50 0,45 0,45 0,40 0,40 0,35 0,35 0,30 0,30 TnT 0,01 ng/ml 47 % 0,25 0,25 Troponin T [µg/l] 0,20 0,15 0,10 0,10 0,05 0,05 NT-proBNP 0,00 84/154 pg/ml 0,00 77 % Before < 15 min post 3 h post 1 d post Before < 15 min post 3 h post Before < 15 min post 3 h post 1 d post Troponin T [µg/l] 0,20 0, * NT-proBNP [ng/l] * * NT-proBNP [ng/l] * * NT-proBNP [ng/l] * * Before < 15 min post 3 h post 1 d post Before < 15 min post 3 h post * * * Before < 15 min post 3 h post 1 d post Am Heart J 2005;150:

5 Endurance exercise and ctnt with longer exercise duration, less athletes were ctnt positive R. Shave et al. MSSE 2007:39:

6 ctnt during exercise 9 well trained men 42.2 km treadmill run ctnt: every 30 min Middleton et al. JACC 2008;52:

7 ctnt: Exercise intensity and duration? Fu and Nie. Int J Sports Med 2009;30:

8 Endurance exercise: ctnt vs. hstnt 6 finisher of the Badwater Ultra-Marathon examined on ctnt no increase in ctnt (below the detection limit) no myocardial damage in well-trained endurance athletes no cross-reactivities between ctnt and CK

9 Endurance exercise and hstnt Giannitsis E, Roth HJ, Leithäuser RM, Scharhag J, Beneke R, Katus HA. Clin Chem 2009;55(3):590-2.

10 hstnt after Marathon 85 marathon runners 47 yrs (45-52) 70 males, 15 females Before, < 1h, 24 h (n=23) The assay with the lowest LOD, the hs-ctnt assay, showed that almost all runners had increased ctn concentrations. The clinical implications of these findings require further investigation. Mingels et al. Clin Chem 2009;55(1):

11 Cardiac biomarkers in AH during and after exercise? Examination of exercised-induced increases in TnT (3rd gen.), hstnt and BNP and cardiac output (spiroergometry) in - endurance athletes with athlete s heart (14,2 ml/kg) - athletes without athlete s heart (12,2 ml/kg) - untrained healthy controls (10,3 ml/kg) at different intensities (70%, 90%, 110% IAT)

12 Standardized exercise in AH: hstnt Extensive Exercise (70 % IAS): 60 min Intensive Exercise (90 % IAS): 60 min High-Intensive Exercise (110 % IAS): ~ 30 min

13 Repeated exercise bouts: hstnt Scharhag-Rosenberger, Hess et al. in preparation

14 Circulation 2007;116:

16 Hypothesis: Troponin Release Bound ctni-c Troponin ctnt-i-c ctnt Free Troponin ctni 24 kd 3-4% ctni + ctnc ctni-c ctnt 37 kd 6-8% ctnt Wu and Feng. Eur Heart J 1998;19(N): N25-N29 Scharhag, George, Shave et al. Med Sci Sports Exerc 2008 Shave, Baggish, George, Gaze, Scharhag, Whyte, Wood, Thompson. JACC 2010

17 Standardized exercise in AH: BNP Extensive Exercise (70 % IAS): 60 min Intensive Exercise (90 % IAS): 60 min High-Intensive Exercise (110% IAS): ~30min Increases BNP

18 BNP [ng/ml] Exercise-induced increases in BNP 110% IAS % IAS 110% IAS % IAS 90% IAS 90% IAS % IAS 70% IAS 70% IAS Rest Athletes with AH (n = 11) Athletes without AH (n = 10) Untrainied controls (n = 9) CO [l/min]

19 Physiological and pathological hypertrophy McMullen et al. Clin Exp Pharm Physiol 2007;34:

20 Cardic biomarkers and DE-MRI Eur J Cardiovasc Prev Rehabil 2006;13:

21 DE-MRI after Marathon Mousavi et al. (Am J Cardiol 2009;103: ) 14 marathon runners (33 ± 6 yrs) TnT, Myoglobin, CK echocardiography: transient changes in RV and LV parameters DE-MRI: no Late Enhancement Hanssen et al. (Clin Sci (Lond.) 2011; ) 46 marathon runners (40 ± 6 yrs) TnT and NT-proBNP before and after Marathon echocardiography (Doppler, TDI), MRI-Tagging (n = 46), LE-MRI (n = 28) increase in TnT, NT-proBNP DE-MRI: no Late Enhancement echocardiography und MRI-Tagging: diastolic function, Twisting

22 Cardiac MRI after Marathon O`Hanlon R,..., Whyte G, Prasad SK (J Cardiovasc Magn Res 2010;12:38) 17 male marathon runners (33 ± 7 yrs) MRI: before and 24 h after 11/17 TnI elevation above AMI cut-off cemri: reduced LV EDV and ESV, small increase in LV-EF, RV unch. in none of the athletes: myocardial inflammation or focal fibrosis... exercise induced cardiac biomarker release is not associated with any functional changes by CMR or any detectable myocardial inflammation or fibrosis. Trivax et al. (J Appl Physiol 2010;108: ) 12 male and 13 female marathon runners (39 ± 9 yrs) TnI and BNP increased after marathon increase in RA and RV index, LA and LV unchanged no morphological changes or evdience for ischemic injury by LGE... does not appear to result in ischemic injury in any chamber.

23 Long term results Life expectancy [yr] 80 Finnische Weltklassesportler (n=2.613) Finnish male world class athletes (Sarna et al.: Med Sci Sports Exerc 1993) Lebenserwartung Increased mean life expectancy mainly explained by decreased cardiovascular mortality (OR: EA = 0.59; TP = 0.61) 60 Ref. Kontrolle Group Power Kraft Athletes LA Team Kurz/Spiele Athletes End. Ausdauer Athletes

24 Long term results Sarna et al. Med Sci Sports Exerc 1993;25:

25 Conclusion Exercise-induced elevations of cardiac biomarkers seem to be a physiologic reaction in healthy hearts......, which also may be relevant for cardiac adaptation to endurance exercise.

27 Cardiac-MRI: Late enhancement Recreational marathon runners between 50 and 72 yrs (57 ± 6) Marathon runners are not automatically healthy subjects! Relation between Marathon und Late enhancement? Möhlenkamp et al. Eur Heart J 2008: 29: Breukmann et al. Radiology 2009 ;251:50-57

28 Eur J Echo 2009;2:

50 marathon runner: 22-59 years (46 ± 12) 28 marathon runner: 60-72 years (63 ± 3) increases in cardiac markers (TnT, NT-proBNP) in 54% of runners no decrease in LV systolic function LV function:

29 50 marathon runner: years (46 ± 12) 28 marathon runner: years (63 ± 3) increases in cardiac markers (TnT, NT-proBNP) in 54% of runners no decrease in LV systolic function LV function: reduction E/A-ratio, no change in E/E RV function: changes in tissue-doppler no relation between cardiac markers and cardiac function no differences in cardiac markers or cardiac function between older and younger marathon runners Knebel et al. JASE 2009;22:

30 Case report Scharhag et al. Dtsch Z Sportmed 2003;54:

31 EJCPR 2006;13: Reproducibility? Nr. Discipl. Age Competition 1 h Exercise 3 h Exercise TNI max TNT max BNP max TNI max TNT max BNP max EF pre EF post TNI max TNT max BNP max EF pre EF post 1 MTB 37 0,50 0, ,03 < 0, ,05 0, MTB 35 0,12 0, ,03 < 0, ,03 < 0, MTB 33 1,50 0, ,06 < 0, ,07 0, MTB 33 0,22 0, ,04 < 0, ,04 < 0, MTB 46 0,22 0, ,03 < 0, ,03 < 0, MTB 36 0,09 0, ,02 < 0, ,02 < 0, Marathon 36 0,10 0, ,06 0, ,04 < 0, MTB 47 0,14 0, ,04 < 0, ,04 < 0, Marathon 33 0,42 0, ,03 < 0, ,03 < 0, Marathon 47 0,19 0, ,06 0, ,04 < 0, Marathon 32 0,15 0, ,02 < 0, ,01 < 0, MTB 44 0,11 0, ,01 < 0, ,02 < 0, MTB 35 0,36 0, ,04 < 0, ,10 0, MTB 31 0,21 0, ,05 0, ,14 0, MTB 29 1,93 0, ,05 < 0, ,07 < 0, MTB 29 0,08 0, ,01 < 0, ,02 < 0, MTB 34 0,63 0, ,04 < 0, ,03 < 0, MTB 25 0,14 0, ,03 < 0, ,01 < 0, MTB 35 0,09 0, ,01 < 0,01 5, ,03 < 0, Marathon 48 0,08 0, ,04 < 0, ,03 < 0,

32 NT-proBNP in Athlete`s Heart th, 90th percentiles 25th, 75th percentiles Median 70 N-BNP [pg/ml] Endurance Athletes Untrained Subjects Scharhag et al. Heart 2004;90:

33 Almeida et al. Cardiology 2002 BNP in Athlete`s Heart cycling athletes young controls

34 BNP in cardiac hypertrophy Institute of Sports and Preventive Medicine McMullen et al. Clin Exp Pharm Physiol 2007;34:

Right ventricular adaptation in endurance athletes. António Freitas. No conflict of interest

The role of echocardiography in sports cardiology Right ventricular adaptation in endurance athletes. António Freitas Cardiology Department - Fernando Fonseca Hospital Lisbon Sports Medicine Centre - Lisbon