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


    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).


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.


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.

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