適者生存： 心臟運動測試的新風貌 Survival of the fittest: A new look at cardiac exercise test

1. 適者生存：心臟運動測試的新風貌Survival of the fittest: A new look at cardiac exercise test 2007物理治療繼續再教育課程 中華民國物理治療學會主辦 慈濟技術學院物理治療系與研發中心承辦 講員：黃千惠

2. 主題大綱 • 傳統心臟運動測試（cardiac ex test，CET）介紹：歷史沿革與方法；強調『運動中』的變化 • 新近心臟運動測試發展：預測死亡率；強調『運動開始』『運動恢復』的變化，主要是心跳 • 文獻回顧：運動後心跳恢復率的預後意義 • 台灣資料：血管正常者之心跳恢復率

3. Cardiac exercise test: CET Cardiac pulmonary exercise test: CPET

4. 傳統心臟運動測試 • 起源：the discovery that exercise in p’t with coronary disease produced ST segment depression • Feil &Siegel (1928) exercised p’t with angina to bring about pain. • They performed stress test by sit-ups. • Master（1929） published paper using pulse and BP to evaluate the cardiac capacity. （His contribution : exercise protocol rather than use of ECG. ）

5. 傳統心臟運動測試重要沿革1 • Goldhammer & Scherf (1932): ST depression was present in 75% p’t with angina and proposed the use of exercise to confirm the diagnosis of coronary ischemia. • Katz & Landt (1935): lead 5 is better in terms of discrimination than lead 4. Use of anoxia to bring changes in ST segment.

6. 傳統心臟運動測試重要沿革2 • Missal (1938): having p’t run up 3-6 flights of stairs and he might be the first to use a max stress test and to the point of pain and emphasized the necessity of taking the recording as quickly as possible thereafter.

7. 傳統心臟運動測試重要沿革3 • Riseman et al (1940): the first to use continuous monitoring and discovered that ST depression appeared before the onset of pain and persisted for a time after the pain subsided. • They concluded that exercise was of little value because of its poor discrimination between the normal and the abnormal subjects.

8. 傳統心臟運動測試重要沿革4 • Johnson et al (1942): developed Harvard Step Test. Use pulse counts during recovery and provide an index of physical fitness. • Hellerstein & katz (1949): ST depression is primarily a diastolic injury current manifested during the TQ interval.

9. 傳統心臟運動測試重要沿革5 • Wood et al: Push the p’t to the max level of their capacity • The amount of work should not be fixed, but adjusted to the individual • The more strenuous work would produce a higher percentage of positive tests • Recommend the use of the stress test to uncover latent myocardial ischemia.

10. 傳統心臟運動測試重要沿革6 • Bruce (1956): work test performed on atreadmill and established guideline that would more or less group p’t into the NYHDC I through IV • Astrand & Ryhming: max oxygen uptake could be predicted by the HR at submax exercise

11. 傳統心臟運動測試重要沿革7 • Blackburn (1969):90% of the ischemic changes could be demonstrated in the CM5 or V5 lead. So spread the use of test outside the research lab. • Conventional exercise test, done with a treadmill, is being supplemented by many other techniques to improve the disgnostic certainty and help localize the disease vessels.

12. 新近心臟運動測試發展 • 功能量（functional capacity）預測死亡率；體適能越佳存活率越高 • 不正常的運動後心跳恢復率與死亡危險性有關 • 心跳加速不能（chronotropic imcompetence）與心跳保留量（heart rate reserve）在測試上的應用

13. 新近心臟運動測試發展1 • Greater fitness results in longer survival (Myers et al, NEJM 2002): • 3679 men with CVD V.S. 2534 men without CVD on treadmill max ET • After adjusting for age, peak exercise capacity measured in METs is the strongest predictor of the risk of death in both groups. • Absolute peak ex ca is a stronger predictor than age-predicted value achieved. • Risk of death doubled among those MET less then 5 when compared to whose MET more than 8

14. Exercise capacity is a more powerful predictor of mortality among men than other established risk factors for CV disease

16. 新近心臟運動測試發展2 • Abnormal heart rate recovery and risk of death • HRR after ex as a predictor of mortality（Cole et al, NEJM 1999） • Slow HRR after ex is associated with carotid atherosclerosis (Jae et al, Atherosclerosis) • Prognostic value of HRR in pt with HF (Arena, Am H J ) • HRR after ex is a predictor of mortality, independent of the angiographic severity of CD (Vivekananthan et al, J Am Col Cardio) • HRR improved as a result of ex training during CR (MacMillan et al, Heart Lung)

17. 運動後心跳恢復率的預後意義 Cole et al, NEJM 1999 12 bpm, 26% abnormal HRR, No further improvement for value above 20

18. A strong association between ↓ ex ca and ab HRR

19. 新近心臟運動測試發展3 • Chronotropic incompetence（心跳加速不能）：最快的心跳數不易達到預期之目標心跳數 • Peak HR is related to age: referred as CI when ＜85％ of the age-predicted HR is achieved. • HR reserve（心跳保留量, HRR）：安靜與最大心跳數之差異 • Azarbal et al found that failure to reach 85％ of the age-predicted maximum HR was predictive of death but that failure to use 80％of HRR was a stronger predictor of risk.

20. 女性功能量常模的預後價值 • The prognostic value of a normogram for ex ca in women(Gulati et al, NEJM 2005): • Ex ca: an independent predictor of mortality • 5721 asymptomatic women underwent a symptom-limited max ex test. • A nomogram established on the basis of age and ex ca • Use the nomogram to determine the % of original women and another 4471 women with CVD

21. ♀: 14.7-(0.13*age) ♂: 14.7-(0.11*age)

22. Active ♀:17.9-(0.16*age) Sedentary ♀: 14.7-(0.12*age)

24. 新近心臟運動測試發展3 • HR reserve approach should be used when assessing HR to ex • The ex test provides critical prognostic information beyond that provided by nuclear imaging • Azarbal et al also found that chronotropic response predicts outcome over and above functional capacity, one of the most powerful predictors of all-cause and cardiac death.

25. 傳統CET V.S. 現代CET

26. 傳統CET V.S. 現代CET

27. 運動後心跳恢復率的臨床意義: 緣起 • 傳統上重視運動中的心跳變化，現發現運動停止後的心跳恢復變化具顯著的臨床意義 • 運動中的心跳的上升變化是副交感退縮與交感興奮的合併結果；運動後的心跳降低則是副交感神經系統再活化的結果 • 因迷走活化的提高經常與死亡率降低相伴發生，研究開始朝向運動後的心跳率與預後因子的關係

28. 運動後心跳恢復率的臨床意義1: 初步發現 • Cole et al 1999：2428 subjects without HD history undergoing symptom-limited ex test. Heart rate recovery (HRR) was defined as the reduction in the HR from the peak ex to one min after the cessation of ex • An abnormal HRR was found using log-rank chi-square test statistic. HRR＜＝12 beats per min is considered abnormal

29. 運動後心跳恢復率的臨床意義2: 非關心疾 • 傳統上認為運動後快速的心跳回復是體適能好的表徵，現在則加上了預後的價值 • Rapid HRR is due to high vagal tone associated with fitness and good health • HRR is prognostic usually at 1 or 2 min after ex in populations related to ex test • Vivekananthan et al: HRR predicts mortality, independent of the angiographic severity of CD

30. 運動後心跳恢復率的臨床意義3: 應用於各類病人

31. 運動後心跳恢復率的臨床意義4: 尋求解釋 • 在心肌梗塞上發現自主神經異常與死亡的密切關係 • 自主神經不平衡（autonomic imbalance）：指迷走神經活動相對或絕對的降低或交感神經活動的升高 • 最普遍的現象是，一旦迷走降低，死亡危險性即升高 • 可證諸baroreflex sensitivity, heart rate variability, and heart rate recovery

32. 血管正常者之心跳恢復率：前言 • 根據先前國外研究結果，推論體適能水準與心跳恢復應有某程度相關（體適能及心跳恢復皆成功預測死亡率） • 肥胖程度與自主神經系統有關（Mona Lisa Hypothesis: most obesities known are low in sympathetic activity） • 副交感神經與脂肪儲存、胰島素釋放有關 • 基於以上結果，推論體適能與肥胖程度應會影響心跳恢復

33. 血管正常者之心跳恢復率：方法 • 本篇研究乃是以接受導管檢查者證實冠狀動脈正常未阻塞者為對象 • 受測者接受 symptom-limited maximal treadmill exercise（Bruce protocol），達90％ age-predicted maximal heart rate reserve者進入接下來之分析 • 將合格之受測者依體適能水準與肥胖程度各分為3組。

34. 血管正常者之心跳恢復率：方法 • 以雙因子變異數分析（two way ANOVA）探討體適能與肥胖（ BMI：body mass index）對心跳恢復的影響 • 體適能：分為below average（BA）, average (A), above average (AA) 三組 • 肥胖：分為NOR（BMI＜25）, OW（25 ≦BMI＜30 ）, OB（BMI≧30）三組 • 心跳恢復：運動停止後的第一分鐘、第三分鐘及第五分鐘之心跳率與運動中最大心跳率之差異，稱為HRR1, HRR3, HRR5

41. 血管正常者之心跳恢復率：結果 • 交互作用未達顯著 • 體適能因子呈顯著(F (2,45) =3.66, p<.05) ，LSD事後比較顯示AA組與A組之HRR1與 HRR3顯著高於BA組 • 肥胖水準因子未達顯著

44. 血管正常者之心跳恢復率：討論 • 本研究發現冠狀動脈血管正常者,體適能水準顯著影響運動後的心跳恢復率; 體適能高於,等於平均者有較高的心跳恢復率 • 與已知趨勢符合, 體適能高→心跳反應及時 • 雖本研究未探討死亡率, 但過去研究結果顯示,體適能高→死亡率低, 心跳恢復率高→死亡率低, 兩者方向一致

45. 血管正常者之心跳恢復率：討論 • 而肥胖的程度對心跳恢復率的影響在本研究中並無發現 • 肥胖對自主神經的影響不一,有的認為腹部脂肪影響較大 • 本研究所使用的肥胖指數為BMI, 無法從BMI得知肌肉骨骼脂肪之相對比例 • 另一思考方向, 所有危險因子的加總結果為血管正常, 亦即肥胖之效果為其他因子所抵銷 • 統計上因素, 肥胖組有較少的人

46. 血管正常者之心跳恢復率：結果 • 在導管證實冠狀動脈正常者之受試者身上, 接受最大運動測試, 達90% 年齡預測心跳保留量者發現, 體適能較佳者有較高之運動後心跳恢復率 • 但在以BMI分類的肥胖指數上, 不同的肥胖指數對運動後心跳恢復率並未造成影響 • 為台灣首度以冠動正常者為對象所完成的運動後心跳恢復率研究, 更多這方面的研究可以幫助我們更進一步了解機轉

47. 要運動多少才夠？ • The amount, intensity, and duration of physical activity required to reduce the risk of coronary heart disease is debated. • Harvard Alumni Study: no further reduction in events associated with CAD in men with an energy expenditure of more than 2000 Kcal per week. • Either a threshold effect or a progressive decline with progressive activity, possibly because of differences in the range of activity in the populations.

48. 要運動多少才夠？ • 大多數文獻將運動強度大於6MET定義為強烈，中度強烈則是產生輕微的喘及達到50％的最大運動強度。 • 一天一個小時中度以上運動即接近最佳狀況，而漸進增加運動量則導致漸進降低心臟危險性。 • ACSM的運動建議是謹慎的，當作一個最低的建議量。More vigorous exercise is probably more beneficial, but also carries a cardiovascular risk, especially for those who are usually inactive.

49. Survival of the fittest適者生存 • Cardiorespiratory fitness enables a person to perform physical activity and is influenced by several other factors, including age, sex, heredity, and medical status. • A nearly linear reduction in mortality was observed as fitness levels increased, and each increase of 1MET in exercise capacity conferred a 12% improvement in survival.

50. 結論 • The lowest threshold for a dose and an intensity that would confer specific survival and cardiovascular benefits is not known. • To compel the clinician to go beyond the identification of risk to the initiation of interventions, such as the prescription of increased physical activity and exercise to modify risk, particularly in patients with low levels of fitness.