(Acute) Deleterious cardiac effects of exercise
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1 (Acute) Deleterious cardiac effects of exercise DR CHRISTOPHE HEDON CHU MONTPELLIER INTRODUCTION 1
2 Introduction Sedentarity = This lifestyle choice is the world's leading preventable cause of non-transmissible death World Health Organisation. World health Report INTRODUCTION 2
3 1- INTRODUCTION 3
4 Trends in United States race finishers (Data from Running USA.) 1- INTRODUCTION 4
5 Evidence from 25 years of Hawaii Ironman racing Lepers R et al. AGE (2013) 35: INTRODUCTION 5
6 Hippocrate All parts of the body, if used in moderation and exercised in labours to which each is accustomed, become thereby healthy and well developed and age slowly; but if they are unused and left idle, they become liable to disease, defective in growth and age quickly. Everything in excess is opposed to nature Hippocrate, 400 years before JC 1- INTRODUCTION 6
7 «Sport paradox» Philippides Philippides, 500 years before JC 1- INTRODUCTION 7
8 «Sport paradox» The sport paradox Philippides, 500 years before JC 1- INTRODUCTION 8
9 Plan 1- INTRODUCTION 2- HEART PHYSIOLOGY REMINDER 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 6- CONCLUSION 9
10 Plan 1- INTRODUCTION 2- HEART PHYSIOLOGY REMINDER 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 6- CONCLUSION 2- HEART PHYSIOLOGY REMINDER 10
11 Heart physiology reminder 2- HEART PHYSIOLOGY REMINDER 11
12 The Cardiac Cycle Ventricular diastole Relaxation Ventricular systole Contraction 2- HEART PHYSIOLOGY REMINDER 12
13 Electrical cardiac activity Potentiel de membrane (mv) Myocyte Automatique Potentiel de membrane (mv) Myocyte Contractile if Ca++ Ca++ 0 K+ Na+ -50 K ms ms R P T S AV H P P Q S HEART PHYSIOLOGY REMINDER
14 Plan 1- INTRODUCTION 2- HEART PHYSIOLOGY REMINDER 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 6- CONCLUSION 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 14
15 A. Acute cardiac adaptations during musclar exercise 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 15
16 A. Acute cardiac adaptations during HEART RATE STROKE VOLUME muscle exercise (bpm) (l/beat) CARDIAC OUTPUT (l/min) 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 16
17 Cardiac output adaptation factors v Myocardial autoregulation: Ø Frank-Starling Ø Heart rate v Nerve regulation by the ANS: Ø Sympathetic Ø Parasympathetic v Hormonal regulation: Catecholamines v Humoral regulation: Local metabolites 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 17
18 Acute cardiovascular adaptations to exercise Dynamic Isometric CO HR SV 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 18
19 B. Chronic Athlete s adaptations: heart: The athlete s chronic adaptations heart Sharma et al. European Heart Journal (2015) 36, ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 19
20 Morphological adaptations Dilatation harmonious and moderate hypertrophy of the four cavities Exercise-induced cardiac remodeling. Weiner RB, Baggish AL. Prog Cardiovasc Dis Mar-Apr; 54(5): ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 20
21 Electrical adaptations Athlete: 45bpm Sedentary: 85bpm 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 21
22 Functional adaptations HR SV The athlete saves his heart rate to the effort The athlete focuses his stroke volume on the effort 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 22
23 Functional adaptations Untrained Athletes VO2 Cardiac output during maximal effort 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 23
24 C. Beneficial cardiovascular effects of physical activity 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 24
25 Relative risks of cardiovascular diseases comparing most active with least active mec 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 25
26 Relative risks of cardiovascular mortality in physically active Vs inactive participants 35% of CV mortality 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 26
27 Benefits for every intensity Intensity Mortality 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 27
28 But for very high intensity? 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 28
29 Plan 1- INTRODUCTION 2- HEART PHYSIOLOGY REMINDER 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 6- CONCLUSION 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 29
30 A. Sudden Cardiac Death 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 30
31 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 31
32 Risk of sudden death in young : cardiomyopathy/channelopathy < 35Y It's not sport that kills but heart disease revealed by sport Corrado JACC ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 32
33 Franklin BA. The role of electrocardiographic monitoring in cardiac exercise programs. J Cardiopulm Rehabil. 1983;3: ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 33
34 Risk of sudden death in the older person: ischemic cardiopathy > 35Y Physical exercise: Hypercoagulation coronary flow Blood pressure Shear stress Myocardial infarction 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 34
35 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 35
36 B. Cardiac dysfunction and cardiac «fatigue» 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 36
37 Left Ventricular Ejection Fraction Left ventricular function immediately following prolonged exercise: A meta-analysis. Middleton N, Shave R, George K, Whyte G, Hart E, Atkinson G Med Sci Sports Exerc Apr; 38(4): MD: middle distance LD: long distance UD: ultra endurance > 9-10h 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 37
38 Left Ventricular Ejection Fraction A recovery of LVEF to pre exercise values is typically observed within 48 h after exercise The effects of prolonged strenuous exercise on left ventricular function: a brief review.mcgavock JM, Warburton DE, Taylor D, Welsh RC, Quinney HA, Haykowsky MJ. Heart Lung Jul-Aug; 31(4):279-92; quiz Left ventricular function immediately following prolonged exercise: A meta-analysis. Middleton N, Shave R, George K, Whyte G, Hart E, Atkinson G Med Sci Sports Exerc Apr; 38(4): MD: middle distance LD: long distance UD: ultra endurance > 9-10h 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 38
39 Left ventricular 23 triathletes strain echocardiography at rest before and immediately after an ultralong distance triathlon Nottin S, Doucende G, Schuster I, Tanguy S, Dauzat M, Obert P. Alteration in left ventricular strains and torsional mechanics after ultralong duration exercise in athletes. Circ Cardiovasc Imaging Jul;2(4): ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 39
40 Left ventricular relaxation alteration 29 subjects (age year) London marathon George K, Oxborough D, Forster J, Whyte G, Shave R, Dawson E, et al. Mitral annular myocardial velocity assessment of segmental left ventricular diastolic function after prolonged exercise in humans. J Physiol Nov 15;569(Pt 1): ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 40
41 Mechanisms? Ø In blood volume cardiac preload ventricular performance withoutdirectly altering cardiac contractility β-adrenoreceptor sensitivity Ø Myocardial dysfunction independent of volume changes Oxidative stress Mechanisms underpinning exercise-induced changes in left ventricular function. Scott JM, Warburton DE. Med Sci Sports Exerc Aug; 40(8): Role of left ventricular untwisting in diastolic dysfunction after long duration exercise. Nottin S, Ménétrier A, Rupp T, Boussuges A, Tordi N Eur J Appl Physiol Feb; 112(2): Prolonged strenuous exercise alters the cardiovascular response to dobutamine stimulation in male athletes.welsh RC, Warburton DE, Humen DP, Taylor DA, McGavock J, Haykowsky MJ J Physiol Nov 15; 569(Pt 1): ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 41
42 Right ventricle > Left ventricle? La Gerche A., Burns A.T., Mooney D.J. Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes. Eur Heart J. 2012;33(8): ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 42
43 C. Evidence of acute myocardial injury CPK MB CPK-MB 24h 4 days Creatine kinase elevations in marathon runners: relationship to training and competition. Siegel AJ, Silverman LM, Lopez RE. Yale J Biol Med Jul-Aug; 53(4): ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 43
44 Cardiac Troponin High-sensitivity cardiac troponin T (hs-ctnt) Concentrations before, immediately after, and 24 and 72 hours after marathon race Scherr J., Braun S., Schuster T. 72-h kinetics of high-sensitive troponin T and inflammatory markers after marathon. Med Sci Sports Exerc. 2011;43(10): ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 44
45 Cardiac Troponin High-sensitivity cardiac troponin T (hs-ctnt) Most studies have not demonstrated a relationship between ctn levels and LV dysfunction Concentrations before, immediately after, and 24 and 72 hours after marathon race Scherr J., Braun S., Schuster T. 72-h kinetics of high-sensitive troponin T and inflammatory markers after marathon. Med Sci Sports Exerc. 2011;43(10): ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 45
46 Mechanisms? Ø Cardiomyocyte membrane permeability by mechanical stress by the production of oxidative radicals by preload-induced increases in stretch-responsive integrins (transient and not affect myocyte viability) Ø Cardiac ischemia proteolysis of the ctn complex troponin degradation products to pass through the cellular membrane without changes in membrane permeability Ø Ischemia? Ø Temporary ischemia produces cell bubbles or blebs in hepatic cell membranes circulation with reperfusion produce increases in plasma ctn Pathobiology of troponin elevations: do elevations occur with myocardial ischemia as well as necrosis? White HD. J Am Coll Cardiol Jun 14; 57(24): ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 46
47 BNP et NT-proBNP Myocardial injury and ventricular dysfunction related to training levels among nonelite participants in the Boston marathon. Neilan TG, Januzzi JL, Lee-Lewandrowski E, Ton-Nu TT, Yoerger DM, Jassal DS, Lewandrowski KB, Siegel AJ, Marshall JE, Douglas PS, Lawlor D, Picard MH, Wood MJ. Circulation Nov 28; 114(22): ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 47
48 BNP et NT-proBNP 95 of 99 collapsed marathon runners demonstrated NT-proBNPlevels within their age-adjusted limits suggesting that exercise-induced elevations in BNP and NT-proBNP are a physiological phenomenon without direct clinical consequences. Cardiac biomarkers, electrolytes, and other analytes in collapsed marathon runners: implications for the evaluation of runners following competition.siegel AJ, Januzzi J, Sluss P, Lee-Lewandrowski E, Wood M, Shirey T, Lewandrowski KB. Am J Clin Pathol Jun; 129(6): Myocardial injury and ventricular dysfunction related to training levels among nonelite participants in the Boston marathon. Neilan TG, Januzzi JL, Lee-Lewandrowski E, Ton-Nu TT, Yoerger DM, Jassal DS, Lewandrowski KB, Siegel AJ, Marshall JE, Douglas PS, Lawlor D, Picard MH, Wood MJ. Circulation Nov 28; 114(22): ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 48
49 Plan 1- INTRODUCTION 2- HEART PHYSIOLOGY REMINDER 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 6- CONCLUSION 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 49
50 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 50
51 A. Atherosclerosis and coronary artery calcification (CAC)? 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 51
52 Regular marathon running does not protect runners from CAC CAC > 100: 35% Mohlenkamp et al. European Heart Journal (2008) 29, POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 52
53 B. Cardiac fibrosis? Endurance exercise athletes in studies fromaustralia (5/40: 13%) La Gerche A., Burns A.T., Mooney D.J. Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes. Eur Heart J. 2012;33(8): to 50% of healthy marathon runner > 50Y Breuckmann et al. Radiology. 2009;25: Endurance exercise athletes in United Kingdom (6/12: 50%) Diverse patterns of myocardial fibrosis in lifelong, veteran endurance athletes.wilson M, O'Hanlon R, Prasad S, Deighan A, Macmillan P, Oxborough D, Godfrey R, Smith G, Maceira A, Sharma S, George K, Whyte G. J Appl Physiol (1985) Jun; 110(6): POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 53
54 Elite middle-aged and veteran endurance athletes (45 75 yr old) who have exercised 10 yr at a competitive level and currently run 30 miles/wk compared with age-matched sedentary controls Plasma markers of collagen syntheses and degradation: Ø TIMP-1 Ø CITP Ø PICP Biochemical evidence of myocardial fibrosis in veteran endurance athletes. Lindsay MM, Dunn FG. Br J Sports Med Jul; 41(7): POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 54
55 D- Atrial fibrillation C. Arrythmias? Atrial fibrillation 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 55
56 655 athletes and 895 control 51±9Y and 93% men Relative Risk = 5,29 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 56
57 Ventricular arrytmias Biffi, et al., AJC POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 57
58 D. Continuum Athlete s heart - Cardiomyopathy 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 58
59 Arrhythmogenic right ventricular dysplasia (ARVC) Autosomal dominant genetic disease (desmosome) 1/1000 1/5000 M > W Adipose infiltration of the myocardium + fibrosis Thinning and localized +/- extensive aneurysms Right ventricular dilatation and dysfunction Ventricular arrhythmias and sudden deaths 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 59
60 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 60
61 87 ARVC with genetic mutation 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 61
62 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 62
63 ARVC and sport: Phenotypical aggravation Animal model (mouse) Kirchhof et al., Circulation POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 63
64 E. Others Doping Aortic size and root dilatation Aging Altitude / Hypoxia Diving Heat. 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 64
65 Plan 1- INTRODUCTION 2- HEART PHYSIOLOGY REMINDER 3- ACUTE AND LONG TERM PHYSIOLOGICAL CARDIAC ADAPTATIONS OF EXERCISE TRAINING 4- ACUTE EXERCISE-INDUCED CARDIOVASCULAR RISKS 5- POTENTIAL MALADAPTATIONS TO LIFELONG EXERCISE 6- CONCLUSION 6- CONCLUSION 65
66 Conclusion O Keef et al. Potential adverse cardiovascular effects from excessive endurance exercise. Mayo Clinic Proc 2012;87: Myocardial injury Adverse remodeling Philippides cardiopathy Arrythmias Sudden death risk Functional alteration Cardiac fatigue Cardiac fibrosis 6- CONCLUSION 66
67 Sharma S et al. Eur Heart J CONCLUSION 67
68 Transient SCD risk Sport paradox Protective effect of regular activity Screening ++, Athlete monitoring Surrounding Rules of good practice 6- CONCLUSION 68
69 Merci 6- CONCLUSION 69
70 To go further Eijsvogels TM, Fernandez AB, Thompson PD. Are there deleterious cardiac effects of acute and chronic endurance exercise? Physiol rev 2016 ;96 : CONCLUSION 70
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