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Heberden coined the term of "angina
pectoris" and described during the late 18th century an entity of chest pain, palor,
sweating, etc. induced mainly by physical exercise. He himself did not relate these
symptoms to the heart but later this connection became gradually obvious. Early this
century, John Harrick from Chicago clinched this connection and made an entity of it
associated with acute myocardial infarction which may or may not terminate in death.
"Angina pectoris" became synonymous with pain induced by decreased blood
supply to the myocardium, due usually to atherosclerosis of the coronary arteries. The
clinical manifestation of this disease was mainly and above all the pain in the left chest
and without the pain, diagnosis of angina pectoris was not made.
This concept has changed with the introduction of continuous monitoring of the
electrocardiogram which demonstrated in the early 70s that episodic ST-depression can
occur during everyday activities frequently without any specific provocation and also
without pain1. The ischemic nature of such
ST-depression episodes was confirmed during the early 1980s by the landmark work of
Deanfield and co-workers, using positron emission tomography (PET) scanning2.
Radionucleide perfusion studies by thallium and later echocardiographically
demonstrated transient wall-motion abnormalities during physical or pharmacological stress
also confirmed that frequently there may be myocardial ischemia without pain3,4. Another benefit of the use of 24-hour monitoring is
our new understanding of the circadian variations in the various manifestations of
ischemia.
Not only do the "ischemic threshold", the frequency of ischemic episodes,
their magnitude etc., change during different periods of the day-and-night cycle5,6. Recently it has been shown that there is an increase
frequency of ischemic episodes between 6 a.m. and noon and the second peak much less
pronounced than the first appears in the late afternoon also ischemic parameters during
exercise testing have been shown to be more prominent during the afternoon hours, as
demonstrated by Dr. de Vries and co-workers7.
A similar early morning surge has been demonstrated in the sympathetic activity in the
plasma catecholamine level, in platelet aggregability and also in the vasomotor tone of
the coronary arteries. The ischemic threshold ie, the heart rate at 1 mm ST-depression was
also shown to peak at around noon, although the parallelism of the phenomenon with the
frequency of ischemic episodes is not perfect.
Holter monitoring enabled also to detect a modest increase in heart rate preceding by
a few minutes an ischemic ST-depression episode. This phenomenon points to an increased
sympathetic tone and consequent increase demand before the start of an ischemic attack in
many patients. Yeung and co-workers8 concluded that
this variety of ischemic episodes responds well to beta-blockers while calcium blockers
could be the therapy of choice in those in whom Holter monitoring does not disclose this
tachycardia phenomenon and in whom therefore a vasospastic mechanism is suspected.
The most investigated triggers of myocardial ischemia is physical exercise,
provocative testing to induce ischemia by exercising the patient are well known since the
1930s when Arthur Master introduced into clinical use his famous "two-step
test". This was followed by the use of a bicycle or treadmill for exercising the
patient. Although mental stress was generally acknowledged for many years to induce an
attack of angina pectoris, only in 1974 was it clearly shown that this can induce an
otherwise unprovoked ischemic episode, even without pain. Barry and co-workers9 and Rozanski et al10
investigated later the effect of mental stress in introducing ischemic episodes which were
mainly silent. Gottdiener and co-workers11 used five
different methods in their patients for introducing mental stress: arrhythmic test using
serial additions, public speaking, mirror tracing, reading and a type A-structured
interview. By any of these methods transient wall-motion abnormalities by echocardiography
could be demonstrated during the mental stress.
Recent studies have shown prognostic significance of the transient ischemic episode
demonstrated by Holter monitoring. Gill et al12 have
shown in the early post myocardial infarction period in 23.4% if the 406 patients studied
ischemic episodes during the monitoring. The presence of such episodes added additional
prognostic information even in those who had abnormal ejection fractions.
The multicenter NIH funded ACIP (asymptomatic cardiac ischemia pilot)13 demonstrated that daily life ischemia diagnosed before
the initial treatment assignment of the patients (angina guided, Holter guided or
revascularized) had independent two-year prognostic significance.
Hikita and co-workers14 studied 25 patients during
exercise testing, Holter and PTCA. The 10 patients with silent ischemia had higher
endorphin levels than the other 15 who had pain. Most interestingly all 10 patients who
were silent during PTCA had no pain also during a positive treadmill test. In line with
this are the results of Dr. Narins and co-workers15,
who showed both high and low somatic pain tolerance in patients having similar degrees of
myocardial ischemia on noninvasive testing. These findings point to the reasonable
postulate that it is not the degree of ischemia, but rather other mechanisms that are
decisive in determining whether or not ischemia is accompanied by pain.
Another mechanism to explain the silentness of ischemia came up with the conclusion
that the explanation lies in the function of the thalamus and the cortex16. Most probably both mechanisms ie, the changes of the
endorphin secretion as well as the reasons located with in the central nervous system as
well as changes in the sympathetic activity are at play in determining whether a patient
will or will not experience pain during an ischemic attack.
New aspects of myocardial ischemic have come to light in the investigation of Dr.
Kubota and his co-workers17, in which they were able to
demonstrate another "early" sign of myocardial ischemia - disturbed autonomic
nervous system function antecedent to a vasospastic episode in patients with variant
angina.
This is an interesting finding in itself that gains additional significance when
related to the report by Dr. Limbruno and co-workers18,
who described data showing the importance of the occlusion site during percutaneous
transluminal coronary angioplasty in eliciting ischemia-induced autonomic imbalance.
These studies further emphasize the ischemic-neural interaction and promote our
understanding of the pathogenesis of ventricular arrhythmias and even of sudden cardiac
death19.
In conclusion, it seems that electrocardiography can demonstrate ischemic episodes,
even without pain in patients with coronary artery disease, with an increased frequency
between 6 a.m. and noon. Mental stress has been shown increasingly the trigger of unproved
ischemic episodes, but silent ischemia is demonstrated also during the provocation of
physical exercise or pharmacologic stress. The prognostic significance of provoked and of
everyday ischemia seems to be well established.
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