Preventive Cardiology

The Role for CPET in the Primary & Secondary Management of Ischemic Heart Disease

Optimizing CV Health with Physiology-Guided Therapy

The role of exercise stress testing in managing patients with heart disease is well documented and essential. At least 25% of coronary patients have sudden death or non-fatal myocardial infarction without prior symptoms 1.  It has been demonstrated in numerous studies that in asymptomatic individuals, the presence of inducible ischemia during exercise is a much better predictor of CV events than symptoms alone 2. Early detection of inducible ischemia enables us to identify patients that will benefit most from more aggressive medical therapy, exercise and lifestyle modification with the goal to stop and reverse early stage heart disease.  This will help to maintain a good quality of life for patients as well as reduce morbidity and mortality.  A recent policy statement from the American Heart Association projects the cost of cardiovascular disease to triple to more than 800 billion dollars per year over the next 20 years.  The statement makes a clear call for more aggressive preventive approaches to contain this epidemic 3.  Targeting asymptomatic individuals with sub-clinical disease will be the only strategy likely to contain this problem from skyrocketing and straining the economy 4.  Chronic disease management ideally begins with an office based risk assessment program 5.

The role of stress testing should be not only to identify the presence of inducible ischemia and/or early stage heart failure but also be used to demonstrate efficacy of therapy with serial testing over time.  Cardiopulmonary exercise testing (CPET) offers this unique ability to not only identify patients with evidence of inducible ischemia and early stage heart failure but also to track disease progression via serial comparison.  The presence of functionally significant ischemia can be due to macrovascular disease or microvascular disease or both.  CPET functions to quantify the global ischemic burden regardless of mechanism and location of lesions.  Since the current data suggests that first line therapy should be medications, lifestyle changes and exercise; defining the exact coronary anatomy becomes less important.  The recently published Medicine, Angioplasty, or Surgery Study (MASS II) was the first randomized controlled clinical trial to report 5-year outcomes of nonsurgical patients with stable multi-vessel coronary artery disease treated with either bare-metal stent placement, coronary artery bypass grafting, or best medical treatment only.  That study showed that optimal medical therapy in patients with stable multi-vessel coronary artery disease resulted in similar long-term outcomes in terms of cardiac-related death or all-cause mortality.  The investigators concluded that “patients with mild to moderate angina can be safely managed medically, whereas PCI or coronary artery bypass grafting ( CABG) is appropriate if symptoms are not adequately controlled by medication or other high-risk features are apparent. 6” The COURAGE and BARI 2D trials also demonstrated no incremental benefit of revascularization on top of optimal medical therapy in patients with stable chronic angina and diabetics with known ischemic heart disease, respectively 7, 8.  However, both trials did find that ~1/3 patients had progression of symptoms despite optimal medical therapy.  Maintaining a low threshold for referring such patients when there is a change in symptom patterns will help to ensure that revascularization is performed at the appropriate time.

Our CPET reports document the ischemic threshold (IT) with a dark black arrow.  The presence of an IT equates to increased risk for cardiovascular events.  The goal of therapy will be to reverse the atherosclerotic process and “make the black arrow disappear” (click to view).  Improvement in heart function as a result of therapy (medication + exercise + lifestyle changes) can be demonstrated with serial testing: 4

  •   Onset of LV dysfunction (abrupt plateau or decrease in stroke volume) at a higher workload or no LV dysfunction noted at all
  •   The non-linear patterns of the cardiac output response (VO2 in panel 1), the stroke volume response (O2-pulse in panel 2) and HR response (panel 3) will normalize and become linear again (representing normalization of LV dysfunction in late exercise)
  •   Higher peak stroke volume (peak O2-pulse) and peak cardiac output (peak VO2) values as a result of decreased myocardial ischemia and improved LV function during exercise.  Peak stroke volume and peak cardiac output are proven independent predictors of mortality in patients with and without heart disease 9, 10.  Increasing peak stroke volume and peak cardiac output in heart disease equates to decreased morbidity and mortality.  These parameters can be used as surrogate markers for this purpose

Met-test offers a superior tool for the early detection and tracking of physiologically significant disease burden with serial testing   without the use of radiation.  Adherences to the customized exercise prescriptions will ensure patients with inducible ischemia are exercising at safe levels. Physiological ischemia (macro or microvascular in origin) is clinically relevant ischemia and must be treated aggressively to improve cardiovascular outcomes.  In that timing is everything, early detection and treatment will be the best cost containing measure over the long haul.  This approach is consistent with professional guidelines as well as the preventive care push currently gaining momentum by policy makers in Washington.

Important Points in Primary & Secondary Prevention of Ischemic Heart Disease 11

  •   “Fixing the plumbing” improves neither the short- nor long-term prognosis of patients with stable coronary heart disease, except for those with high-grade left main stenosis or severe proximal 3-vessel disease.  However, more recent outcomes data reveals that revascularization does not provide incremental cardiovascular benefit on top of optimal medical therapy in patients with multi-vessel coronary artery disease including left main and triple vessel disease 12.
  •   Although revascularization improves angina in CAD patients, it does not alter the incidence of MI or death compared with aggressive medical therapy alone
  •   In the COURAGE trial, optimal medical therapy resolved angina in 70% of subjects by the end of 5 years
  •   The BARI 2D trial found that aggressive medical therapy in type 2 diabetics was as effective as elective coronary revascularization for reducing death and CV events
  •   Arterial inflammation and endothelial dysfunction play central roles in determining prognosis and angina status of patients with stable angina and in patients with evidence of inducible ischemia on stress testing
  •   A combination of therapeutic lifestyle changes and multi-drug regimen can normalize and neutralize the atherogenic milieu thereby markedly decreasing the risk of adverse CV events and the need for revascularization.
  • Modifiable CV Risk Factors:
      1. Hypertension
      2. Dyslipidemia
      3. Diabetes
      4. Smoking
      5. Sedentary lifestyle
      6. Obesity
  • Treatment Modalities:
      1. Calcium Channel Blockers in HTN amlodipine
      2. Statins +/- Niacin (LDL < 70 and HDL > 50)
      3. Aspirin
      4. Omega-3 fatty acids (Fish Oil)
      5. Vitamin D
      6. Alcohol
      7. Diet
      8. Exercise: customized exercise prescription from CPET to improve endothelial dysfunction, collateral circulation and anti-inflammatory benefits at safe work loads
      9. Stress Management: meditation, yoga, pets, religion, etc.

1. Myerburg RJ, Kessler KM, Castellanos A. Sudden cardiac death: epidemiology, transient risk, and intervention assessment. Ann Intern Med. 1993; 119:1187-1197.

2. Gehi AK, Ali S, Na B, et al. Inducible ischemia and the risk of recurrent cardiovascular events in outpatients with stable coronary heart disease. The Heart and Soul study. Arch Intern Med 2008; 168:1423-1428.

3. Heidenreich et al. Forecasting the Future of Cardiovascular Disease in the United States: A Policy Statement from the American Heart Association. Circulation. 2011; 123:00-00.

4.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.

5. Smith SC, Greenland P, Grundy SM. AHA Conference Proceedings: Prevention conference V: beyond secondary prevention: identifying the high-risk patient for primary prevention: executive summary: AHA. Circulation. 2000; 101:111-116.

6. Hueb W, Lopes NH, Gersh BJ, Soares P, Machado LA, Jatene FB, Oliveira SA, Ramires JA. Five-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease. Circulation 2007; 115:10820-1089.

7. Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503-1516.

8. Frye RL et al for the BARI 2D Study Group. A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease. N Engl J Med 2009; 360:2503-2515.

9. Oliveira RB, Myers J, Ara jo CG, Abella J, Mandic S and Froelicher V. Maximal exercise oxygen pulse as a predictor of mortality among male veterans referred for exercise testing. Eur J Cardiovasc Prev Rehabil 2009; 16:358-364.

10. Oliveira RB, Myers J, Ara jo CG, Arena R, Mandic S, Bensimhon D, Abella J, Chase P, Guazzi M, Brubaker P, Moore B, Kitzman D, Peberdy MA. Does Peak Oxygen Pulse Complement Peak Oxygen Uptake in Risk Stratifying Patients With Heart Failure? Am J Cardiol 2009; 104:554-558.

11. O'Keefe JH, Carter MD, Lavie CJ. Primary and Secondary Prevention of Cardiovascular Diseases: A Practical Evidence-Based Approach. Mayo Clln Proc. 2009; 84(8):741-757.

12. Schouten O, Kuijk JP, Flu WJ, Winkel TA, Welten GM, Boersma E, Verhagen HJM, Bax JJ, Poldermans D. Long-Term Outcome of Prophylactic Coronary Revascularization in Cardiac High-Risk Patients Undergoing Major Vascular Surgery (from the Randomized DECREASE-V Pilot Study). Am J Cardiol 2009;103:897-901.

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