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Return to Higher Level Activities for Cardiac Patients Niall M. Moyna, DCU Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Exercise Paradox! Evidence for transient elevation in risk with exercise, countered by a protective effect of regular exercise Aging and SCD Middle-aged and older athletes are at significantly higher risk for sudden cardiac death (SCD) compared with younger athletes SCD - Current Burden • 13 per 100,000 joggers/year • 0.8 to per 100,000 marathon runners (retrospective studies) General Population Annual incidence of 4.6 sports-related SCDs per 1 million residents Age and Sports-Related Sudden Deaths Overall population Competitive athletes Overwhelming majority of sports-related sudden deaths occur among those ≥ 35 years of age J Am Col Cardiol, 65, (5), 2015, 493 – 50, 2015 Circulation. 2011;124:672-681,2011 Eloi Marijon et al. Circulation. 2011;124:672-681, 2011 Sports Engaged at the time of Sudden Death N = 820 6% (50 of 820) of all cases of sports-related SCDs involved young, competitive athletes Primarily men US Athletes Completing Road Races State of the Sport - Part III: U.S. Race Trends. Running USA. July 9, 2014. http://www.runningusa.org/2014-state-of-the-sport-part-III-us-race-trends Exercise Paradox Long Term Protective Effect vs. Transient Risk of Exercise Risk of SCD during strenuous exercise 60 Relative Risk 50 56 Sedentary High Fit Men with the highest habitual level of PA have a 60% lower relative risk of global SCD compared with sedentary controls 40 30 20 10 0 5 Siscovick et al., N Engl J Med 311, 874-7, 1984 5-fold residual risk Overall RR = 16.9 SCD RR within 30 min of Vigorous Exercise 80 70 Relative Risk 74 60 <1/wk ≥ 5/wk 50 40 30 20 10 11 0 Albert et al., N Engl J Med 343, 1355-61, 2000 Myocardial Infarction RR During Exercise 120 Relative Risk 100 50-fold difference Sedentary 107 Active 80 60 40 20 2.4 0 Mittleman et al., N Engl J Med 329, 1677-83, 1993 Global Benefits of Exercise • Global mortality benefits of exercise far outweigh the risk • Regular exercise of mild to moderate intensity provides a 7-10 fold risk reduction for SCD • Regular exercise of mild to moderate intensity provides a 50-fold risk reduction for MI • Dose-related beneficial impact of regular exercise on global CV risk - independent of sex, ethnicity, and probably of age Nerve Fibres Skeletal Muscles B\rain Myostatin Liver IL-10 IL-6 IL-15 Adipose Tissue IL-1 IL-7 IL-4 SPARC IL-13 Follistatin Iriscin Myonectin Visfatin BDNF IGF/PI3K/Akt Endothelial Cells Heart SIRT1 IL-8 Spinal Cord sTNF-R Immune System Pituritary Gland Fat metabolism Neuroplasticity Motor unit regeneration Endothelial repair Endothelial function Revascularization Muscle growth Muscle repair Antiinflammatory Anti-obesogenic Insulin-sensitizing Thermogenesis Vasculogenesis Glucose metabolism Cancer cell proliferation Myocardial remodelling Endurance Exercise Physiological Cardiac Remodelling Efficient fuel handling Bi ventricular Hypertrophy Angiogenesis Coronary blood flow Hyperplasia Altered Ca2+ handling Improved EDD O2 extraction Capillary density Enhanced systolic function Enhanced diastolic function Mitochondrial Improved biogenesis contractility Exercise Induced Cardiac Remodeling Key Signaling Pathways Exercise-Induced SCD Mechanisms • • • • • • CAD account for up to 80% Hypertrophic cardiomyopathy Arrhythmogenic right ventricular dysplasia Myocarditis Valvular heart disease Small distinct subgroup - unexplained CAD Associated SCD Mechanisms Ischemic ventricular arrhythmia – final common pathway • Exercise related sympathetic activation – may sensitize vulnerable myocardium to ischemia and arrhythmias • Electrolyte and metabolic factors – prolonged exercise • Activation of haemostatic and thrombosis in response to plaque rupture • Hemodynamic effects of vulnerable coronary plaque CAD Associated SCD Mechanisms Plaque morphology in men whose death was temporally linked to physical or emotional stress versus men who did at rest Acute Plaque Rupture Intra Plaque Haemorrhage 80 70 80 68 70 Stress Rest 50 40 23 Stress 60 Percent Percent 60 30 71 50 Rest 41 40 30 20 20 10 10 0 0 Burke et al., JAMA, 281; 2015, 921-926, 1999 Plaque Rupture with Exertion and at Rest Characteristics Remote Vasa Vasorum Subjacent High Exercise Levels Potential Hazards • Quantified CAC in 108 experienced male marathon runners > 50 years of age • CAC score ≥100 was present in 36% of runners (not different from age-matched controls, even though the FRS was much lower) • CAC score exceeded controls matched for age and FRS • 12% had detectable LGE in patterns with diffuse myocardial scarring • Presence of myocardial LGE predicts cardiac events in patients with CAD • In marathon runners, such damaged myocardium may be a substrate for an susceptibility to cardiac arrhythmias in response to exercise-related catecholamine levels Estimates of Event-Free Survival by Extent of CAC 8% 14.3% Stefan Möhlenkamp et al. Eur Heart J 2008;29:1903-1910 Marathon Right Ventricle • Repeated RV insult, injury and fibrosis that can evolve late into substrate for ventricular arrhythmias • Elevated RV pressures and dimensions at conclusion of marathons • 2x elevation in B type-NP and Trop-T in 60% with 40% exceeding the threshold for diagnosis of MI • levels of biomarkers related to i) impaired LV diastolic function, ii) pulmonary artery pressure and iii) RV dysfunction • More severely effected in the least well-trained vs best Exercise Myocardial Ischemia Noel M, Eur Heart J. 28(13):1559-65, 2007 Compared intense and prolonged exercise training above the threshold for myocardial ischemia -1 mm ST-segment depression) Randomization Control (N = 9) Ischemia (n=11) • CR training 3 d/wk for 6 wk • CR training 3 d/wk for 6 wk • As per guidelines (i.e. 10 bpm < HR • 5-10 min warm-up @ light intensity @ 1 mm ST-segment depression • 20-60 min endurance exercise @ intensity = 1 mm but no more than 3 mm of STsegment depression • 15 min strength training • 10 min cool down • cTnT at 18-24 h after the first 20, 40, and 60 min of continuous training • Corresponded to the 1st, 12th, and 21st exercise sessions • cTnT again after the first 3 sessions that involved 60 min of end exercise Repeated Bouts of Exercise Induced Ischemia Patients with Stable IHD • • • • Well tolerated Not deleterious No malignant or significant arrhythmias while exercising No malignant or significant arrhythmias during Holter monitoring • No myocardial injury (cTnT levels) • No sustained LV systolic dysfunction • No change LV systolic & diastolic dimensions Results suggest that progressive exposure to repeated ischemic exercise periods is not pro-arrhythmic Exercise Above the Ischemic Threshold and Serum Markers of Myocardial Injury M. Juneau et al. 2009 Effects of a single session of exercise above the IT on biochemical markers of myocardial injury in stable coronary pts in response to exercise-induced ischemia Random order 72 hr Session 1 Session 2 Tm Exercise (20 min) HR < IT TM Exercise (20 min) (~10 bpm < HR associated with the appearance of an ST segment depression ≥1mm) (~10 bpm > HR associated with the appearance of an ST segment depression ≥1mm) CK CK-MB Troponin T CK CK-MB Troponin T HR > IT 6 h & 24 h after session No CK, CK-MB or troponin T Results Data presented as mean ± SD. Normal ranges: CK 24 U/L to 195 U/L; CK-MB isoenzyme 0 U/L to 30 U/L; troponin T < 0.1 ng/mL. No significant differences noted for all comparisons High-Intensity Interval Exercise (HIIE) Definition Series of repeated bouts of short duration ( 5 min) high intensity exercise (70 – 100% of maximal effort), alternated with periods of active or passive recovery Optimisation of High Intensity Interval Exercise in CAD T. Guiraud et al. Eur J Appl Physiol, 108, 733-740, 2009 • Compared 4 diff bouts of HIIE (cycling) on time to exhaustion, time spent near VO2max , and comfort and safety in pts (N = 20, Age = 65± 8, VO2max = 27.1± 6.7) with stable CAD • Hx of ≥ 70% arterial diameter narrowing of ≥ 1major coronary artery., prior MI and perfusion defect on exercise nuclear imaging • 8 min standardised warm up followed by 5 min passive recovery A C B D HIIE Modes Typical VO2 Response of a Participant During each HIIE Mode Acute Responses VO2max VO2max 95% 85% 80% 95% 80% 80% A B C D 15/15 15/15 60/60 60/60 Passive Recovery Active Recovery Passive Recovery Active Recovery ‡ ‡ A v C p<0.06 Reached VO2max: A= 13(68%); B = 17(89%); C= 15(79%); D= 14(73%) Acute Responses to High-Intensity Intermittent Optimisation of High Intensity Interval Exercise Exercise in CAD in CHD Patients T.T.Guiraud et al. MedEur Sci JSports 43, 108, 211-217, 2011 2009 Guiraud et al. Appl Exerc, Physiol, 733-740, • Compared the acute cardiovascular physiological responses between high intensity interval exercise (HIIE) and moderate intensity continuous exercise (MICE) of similar energy expenditure in men and women (N = 20, Age = 62±11, VO2max = 28.4± 9.1) with CHD • Compared the acute ST segment changes, ventricular arrhythmias, blood pressure and cardiac troponin T (cTnT) between HIIE and MICE of similar energy expenditure in CHD pts Max Relative Power MICE HIIE Relative Power 10 min 100% 10 min 70% 15 sec 15 sec 50% 10 min WU 4 min PR 5 min WD 27.8 min Time To Exhaustion Ventilation RPE Achieved 35 min of exercise Max Acute Responses to High-Intensity Intermittent Exercise in CHD Patients T. Guiraud et al. Med Sci Sports Exerc, 43, 211-217, 2011 Group Values are absolute number (%) and mean ± SD; ‡ p<0.001 vs HIIE HIIE MICE Ventricular arrythmias 0 0 Abnormal BP responses 0 0 Prolonged ischemia 0 0 >2mm ST depression 0 0 Demonstrable ST dep (< 2 mm)* 3 0 Maximal ST depression 1.2 ± 0.3 *ST segment normalising during 15 s recovery period Cardiac troponin C (mg/L) - rest < 0.04 < 0.04 Cardiac troponin C (mg/L) - 20 min < 0.04 < 0.04 Cardiac troponin C (mg/L) – 24 h < 0.04 < 0.04 49.8 ± 8.2 58.9 ± 14.2‡ 14 ± 2 16 ± 2 Values are means SD Ventilation (L/min) RPE HIIE Protocol Block 3 8 x 45 s HII 2 min Seated Rest 2 min Seated Rest Warm-Up %HRpeak 50% 2 min Seated Rest 90% Block 2 8 x 45 s HII 2 min Seated Rest Block 1 8 x 45 s HII Cool Down 10 min Total Session Time: 47 min Total HIIE: 18 min 5 min 45 s High-intensity Intervals 15 s Passive Recovery ECG Changes & Clinical Symptoms HIIE • HIIE – safe for study participants • ST-segment changes ranged from 1 – 3 mm, and returned to normal during passive recovery • None of the participants reported angina symptoms during the acute bout of SRE or HIIE • Ventricular ectopics – single and couplets Sept 2014 • Evaluated whether excessive exercise is associated with progressively lower mortality after a cardiac event in 2377 self-identified MI survivors • Estimated energy expended from running or walking • EE was measured as metabolic equivalents (3.5 mL O2/kg per min per day or metabolic equivalent of task-h/d [METh/d]) • 1 MET-h/d is the energy equivalent of running 1 km/d Sept 2014 1. 2. 3. 4. 5. 6. <1.07 MET-h/d 1.07 -1.8 MET-h/d 1.8 - 3.6 MET-h/d 3.6 - 5.4 MET-h/d 5.4 – 7.2 MET-h/d ≥7.2 MET-h/d Inadequately active Satisfies current PA recommendations (150 min MI or 75 min VI) Exceeds recommendations 1-2x Exceeds recommendations 2-3x Exceeds recommendations 3-4x (15-23 miles/wk) Exceeds recommendations ≥4x (23-30 miles/wk) Sept 2014 • Greater exercise EE by walking and running was associated with a significantly lower risk for CVD related mortality in proportion to the exercise dose through 7.2 MET-h/d • EE ~ equivalent to running 30 miles (50 km)/week or • Walking briskly 46 miles (75 km)/week • Increased risk relative to less active runners at EE > 30 miles/wk • Unrelated to traditional risk factors CVD Mortality N=2377 Energy Expenditure Harard Ratio 1.0 0.8 0.6 0.88 1 0.4 0.501 21% 0.2 0.0 0.764 0.786 <1.07 24% 1.07-1.8 1.8-3.6 Guidelines Williams et al., Mayo Clin Proc, 2014 50% 0.369 63% 3.6-5.4 5.4-7.2 15-23 23-30 Energy Expenditure (MET-h/d) >7.2 15.4% in risk for CVD related mortality per MET-h/d between 0 and 7.2 MET-h/d 2.62-fold risk for CVD related mortality per MET-h/d above 7.2 MET-h/d relative to the risk at 7.2 MET-h/d Williams et al., Mayo Clin Proc, 2014 Conclusions • Exercise induced Ischemia not always bad • Recommend short duration events • Aging combined to CAD may increase risk for MI and SCD • Individual approach • Common sense • More research needed!!!