Ischemic Myocardial Dysfunction

Optimizing CV Health with Physiology-Guided Therapy

Ischemic heart disease (IHD) is caused by either obstruction of the large epicardial arteries (macrovascular ischemia) or small vessel dysfunction (microvascular ischemia) or both.  Atherosclerosis affects all segments of the coronary arterial tree and in different ways in men and women.  The first step in the evaluation of IHD should be to assess for the presence of an ischemic burden during exercise.  The presence of an ischemic burden will result in a decline in LV function at work rates at or above the ischemic threshold (IT).  During a CPET, exercise-induced left ventricular (LV) dysfunction is detected by assessing cardiac output (VO2), stroke volume (VO2/HR) and HR response in real time during exertion 1, 2.   An abrupt decrease in cardiac output (abrupt decrease in the slope of VO2 uptake trajectory) results from a decreasing stroke volume with increasing work rate and concomitant steepening of HR response after the IT.  An abruptly steepening HR response proves the presence of a physiologically significant and hence clinically important ischemic burden because this is an indirect mechanism that is forced into play during exercise to compensate for a decreasing stroke volume after the onset of ischemia.  One principle has become clear the higher the underlying global ischemic burden, the more pronounced exercise-induced LV dysfunction becomes on CPET.

Mechanisms of Inducible Myocardial Ischemia

After the identification of a physiologically significant ischemic burden, the next question is the origin of the ischemia. CPET is exquisitely sensitive to the presence of ischemia at early stages but is not specific to the mechanism:

Non-atherosclerotic causes of Ischemia

    1. Hypertensive BP response (SBP > 220 mmHg)
    2. Valve disease   aortic stenosis
    3. Congenital heart disease    anomalous coronary anatomy, IHSS, myocardial bridging
    4. Hypertrophy (LVH)    subendocardial ischemia
    5. Coronary vasospasms

Atherosclerosis

    6. Macrovascular disease    obstructive macrovascular (epicardial) disease
    7. Microvascular disease    endothelial dysfunction & occlusive microvascular disease with impaired coronary reactivity

Ischemia detected by CPET reflects the net effect of all of these mechanisms during exertion. In our experience, macrovascular ischemic heart disease detected by CPET that is typically missed on myocardial perfusion studies (nuclear - MPI) includes “balanced ischemia”.  Balanced ischemia is typically caused by left main coronary disease & triple vessel disease. Such patients typically have high ischemic burdens and a poor short term prognosis,  especially when angina symptoms are present.  Other types of lesions detected include isolated RCA disease and stent occlusion.

Microvascular ischemia is confirmed at the time of cardiac catheterization by measuring the coronary flow reserve (CFR).  Reduced CFR can be due to endothelium and non-endothelium dependent mechanisms and confirms the presence of physiologically significant microvascular ischemia.  Contrary to earlier beliefs, microvascular ischemia is not a benign condition and has been demonstrated to result in increased cardiovascular events (myocardial infarction, stroke, hospitalization for heart failure and sudden cardiac death) 3-5.   The microvascular ischemic burden in society is grossly under-diagnosed and grossly under-treated, particularly in women, diabetics and CAD patients with chronic angina 6-10.  Current clinical cardiac tools are not adequate in identifying microvascular ischemia, which in turn is resulting in increased morbidity, mortality and cost to the healthcare system 6, 7.  Such patients respond well to potent anti-ischemic medical therapy and can safely undergo exercise rehabilitation as a treatment modality with a customized exercise prescription made possible through CPET (exercise at heart rates below the ischemic threshold).

Management

Patients with atherosclerosis must undergo aggressive lifestyle medication, medical therapy and exercise therapy to stop and reverse the atherosclerosis process and thus to decrease future CV events. Symptom control (anti-anginal therapy) should be customized based on peak HR and peak stroke volume response on the CPET study.  This  physiology-guided approach enables more effective customization of therapeutic regimens.

Serial CPET testing will enable close tracking of ischemic burden and clinical status. Complete reversal of ischemic burden will normalize an abnormal baseline CPET study and increase exercise capacity (peak VO2) 11.  A higher exercise capacity equates to a better prognosis.

Patients with non-atherosclerotic causes of inducible ischemia must be evaluated further based on history.  To learn how to use our expertise to more effectively evaluate and manage patients with ischemic heart disease, contact us.

Conclusion

The best fit for CPET is the first test in the cardiac evaluation of all patients to determine if a problem actually exists and to help determine the direction for further evaluation & management. A normal CPET study has powerful negative predictive value as the study has demonstrated that there is no physiologically significant cardiac dysfunction during exertion. Patients with normal cardiac physiology are not likely to have bad outcomes and further evaluation is likely to be unproductive. In patients with abnormal baseline studies, close clinical tracking will enable more precise management to ensure that disease treatment is headed in the right direction and that morbidity and mortality are reduced long term.

1. Gulati M, Cooper-DeHoff RM, McClure C, Johnson BD, Shaw LJ, Handberg EM; Zineh I; Kelsy SF, Arnsdorf MF, Black HR, Pepine CJ, Merz CN. Adverse Cardiovascular Outcomes in Women with Nonobstructive Coronary Artery Disease. Arch Intern Med. 2009; 169(9):843-850.

2. Sicari R, Rigo F, Cortigiani L, Gherardi L, Galderisi M, Picano E. Additive Prognostic Value of Coronary Flow Reserve in Patients with Chest Pain Syndrome and Normal or Near-Normal Coronary Arteries. Am J Cardiol 2009; 103:626-631.

3. Humphries KH, Pu A, Gao M, Carere RG, Pilote L. Angina with "normal" coronary arteries: sex differences in outcomes. Am Heart J 2008; 155:375-81

4. Merz, CN, Shaw LJ, Reis SE, et al. Insights from the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation (WISE) study. J Am Coll Cardiol 47, N0. 3 Supp S: 21S-9S.

5. Anita P, Shufelt C, Merz CN. Persistent Chest Pain and No Obstructive Coronary Artery Disease. JAMA. 2009; 301(14):1468-1474.

6. Bellardinelli B, et al. Exercise induced myocardial ischemia detected by cardiopulmonary exercise testing. European Heart Journal (2003); 24; 1304-1313.

7. J.-P. Schmid: Detection of exercise induced ischaemia: a new role for cardiopulmonary exercise testing. European Heart Journal (2003) 24: 1285-1286.

8. Belardinelli R: Cardiopulmonary exercise testing: the exercise stress test of the future? Italian Heart Journal Supplement (2005) Feb; 6(2): 77-84.

9. Chaudhry S, Ross A, Wasserman K, Hansen JE, Lewis GD, Myers J, Belardinelli R, Labudde B, Menasco N, Boden WE. The utility of cardiopulmonary exercise testing in the assessment of suspected microvascular ischemia. Int J Cardiol 2009.

10. Chaudhry S, Ross A, Wasserman K, Hansen JE, Lewis GD, Myers J, Chronos N, Boden WE. Exercise-induced myocardial ischemia detected by cardiopulmonary exercise testing. Am J Cardiol 2009; 103:615-619.

11. Chaudhry S, Arena R, Hansen JE, Lewis GD, Myers J, Sperling L, LaBudde B, Wasserman K. The Utility of Cardiopulmonary Exercise Testing to Detect and Track Early Stage Ischemic Heart Disease. Mayo Clin Proc. 2010;85(10):928-932.

12. Janand-Delenne B, et al. Silent Myocardial ischemia in patients with diabetes, who to screen. Diabetes Care 1999:22:1396-140.

13. Inoguchi T, Yamashita T, et al. High incidence of silent myocardial ischemia in elderly patients with NIDDM. Diabetes Research and Clinical Practice 2000:47;37-44.

14. Zafrir N, et al. Relation between aerobic capacity and extent of myocardial ischemia in patients with normal cardiac function. Am Heart J 1999;138:1088-1092.

15. Bussotti M, et al. Cardiopulmonary evidence of exercise-induced silent ischaemia. European Journal of Cardiovascular Prevention and Rehabilitation 2006; 13:249-253.

16. Contini M, et al. Cardiopulmonary exercise test evidence of isolated right coronary artery disease. International Journal of Cardiology 2005.09.033.

17. Klainman E, Kusniec J, Stern J, Fink G, Farbstein H. Contribution of cardiopulmonary indices in the assessment of patients with silent and symptomatic ischemia during exercise testing. Int J Cardiol 1996; 53:257–263.

18. Klainman E, et al. Assessment of functional results after percutaneous transluminal coronary angioplasty by cardiopulmonary exercise test. Cardiology 1998; 89:257-262.

19. Munhoz EC, Hollanda R, Vargas JP, Silveira CW, Lemos AL, Hollanda RM, et al. Flattening of oxygen pulse during exercise may detect extensive myocardial ischemia. Med Sci Sports Exerc 2007; 39:1221–1226.

20. Meyer K, Samek A, Pinchas A, Baier M, Betz P, Roskamm H. Relationship between ventilation threshold and onset of ischemia in ECG during stress testing. Eur Heart J 1995; 26:623–630.

21. Fortini A, Bonechi F, Taddei T, Gensini GF, Malfanti PL, Neri Serneri GG. Anaerobic threshold in patients with exercise-induced myocardial ischemia. Circulation 1991; 83 (Suppl):11–50.

22. Itoh H, Tajima A, Koike A, Osada N, Maeda T, Kato M, et al. Oxygen uptake abnormalities during exercise in coronary artery disease. In: Wasserman K, editor. Cardiopulmonary exercise testing and cardiovascular health. Armonk: Futura Publishing Company; 2002. pp. 165–172.

23. Takaki H, Sakuragi S, Nagaya N, Suzuki S, Goto Y, Sato T, et al. Post exercise VO2 Hump phenomenon as an indicator for inducible myocardial ischemia in patients with acute anterior myocardial infarction. Int J Cardiol 2006; 111:67–74.

24. Milani R, Lavie C, Spiva H. Limitations of estimating metabolic equivalents in exercise assessment in patients with coronary artery disease. Am J Cardiol 1995;75(14); 940-942.

25. Tajima A, Itoh H, Osada N, Omiya K, Maeda T, Ohkoshi N, Kawara T, Aizawa T, Wasserman K. Oxygen uptake kinetics during and after exercise are useful markers of coronary artery disease in patients with exercise electrocardiography suggesting myocardial ischemia. Circ J. 2009 Oct; 73(10):1795-6.

26. Pinkstaff S, et al. The Clinical Utility of Cardiopulmonary Exercise Testing in Suspected or Confirmed Myocardial Ischemia. Am J Lif Med 2009. doi:10.1177/1559827610362955.

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