Circulation. 2005;111:e435-e437
doi: 10.1161/CIRCULATIONAHA.105.550723
(Circulation. 2005;111:e435-e437.)
© 2005 American Heart Association, Inc.
Symptoms Other Than Chest Pain May Be Important in the Diagnosis of "Silent Ischemia," or "The Sounds of Silence"
Shlomo Stern, MD
From Hebrew University of Jerusalem, Jerusalem, Israel.
Correspondence to Dr Shlomo Stern, FAHA, 1 Shmuel Hanagid St, Jerusalem 94592, Israel. E-mail sh_stern{at}netvision.net.il
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Introduction
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"Silence like a cancer grows."
Paul Simon, ©1964
Case presentation: In 2001, on routine testing, a 58-year-old man with a family history of heart disease had an above-normal cholesterol level and high blood pressure. His medical recommendation was to eat fewer fast foods and to take anticholesterol medication, which was stopped when his cholesterol level became lower. His blood pressure problem was treated successfully. His stress test was successful, and he started to exercise 2 to 3 times per week, in addition to adopting the South Beach Diet. The patient did not complain about chest pain, and there was no recommendation for any further cardiac diagnostic testing. Acute shortness of breath and mild chest pain in 2004 prompted a coronary angiogram, which necessitated an immediate quadruple-bypass surgery. The patient later expressed his opinion that people with family history, high cholesterol, and high blood pressure ought to consider an angiogram even if they dont have symptoms.
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Background
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It is estimated that in the United States today, between 2 and
3 million people with stable coronary artery disease (CAD) have
evidence of asymptomatic ischemia. It is accepted that

20% of
the nonsudden cardiac deaths and nearly half of the sudden cardiac
deaths occur with preexisting but undiagnosed CAD.
1 An important
objective of contemporary clinical cardiology, therefore, should
be the uncovering of the silent and therefore unsuspected disease,
with the hope of reducing thereby the incidence of cardiovascular
events or even death in susceptible individuals. With this in
mind, the American Heart Association Prevention V Conference
2 proposed the use of office-based testing and additional noninvasive
procedures in selected patients.
It has become accepted that the presence of 1 or more of the classic risk factors of CAD, even without typical chest pain, and conversely, typical chest pain even without risk factors necessitates cardiac evaluation. There is concern, however, about those relatively younger people who do not have diagnosed risk factors and who do not present with chest pain. Are there other subjective manifestations that can or may be a symptom for subclinical coronary atherosclerosis inducing myocardial ischemia? Are there expressions other than pain that are imperative to call to the attention of the patient, of the primary care physician, and even more so, of the clinical cardiologist regarding the possibility of the presence of silent myocardial ischemia, requiring further testing?
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Dyspnea
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Shortness of breath is frequently considered by a physician
as not being a serious warning sign; it could be passed off
as undue physical exertion, emotional arousal, or even as the
result of a lung condition possibly induced by smoking. A direct
connection between dyspnea and an ischemic myocardium is not
fully recognized, and most frequently, this symptom is considered
related to heart failure. Dyspnea alone, without chest pain,
as a clear sign of a positive exercise test was described in
1968 by Phibbs and coworkers,
3 who found this symptom alone
in 25.6% of patients at the time of an ECG-positive exercise
test, whereas classic anginal pain was experienced by only 17.3%
of the examinees. In a large series of patients referred for
evaluation of dyspnea,
4 42% with this symptom alone had ischemia
on exercise echocardiography versus 19% who had chest pain.
During a 3-year follow-up, death and nonfatal infarction occurred
significantly more often in patients with dyspnea than in those
without. Hyperventilation may also be a "sound of silence,"
because it was included among the atypical symptoms evaluated
in an elderly population for angiographic CAD and was not different
from typical anginal pain for predicting the presence of CAD
in either gender.
5
Breathlessness alone can be the presenting symptom even for acute coronary syndrome and was found to be present in 26% of patients in the EuroHeart data set.6 Brieger and coworkers7 found that among the 8.4% of the patients who presented without chest pain, nearly half of them had dyspnea only. The patients with dyspnea or with other painless presentations of unstable angina had greater morbidity and a higher mortality. We8 have shown that atypical manifestations of the acute coronary syndrome, including dyspnea, become significantly more frequent with advancing age.
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Dyspnea in the Diabetic Patient
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Diabetic patients with shortness of breath as the predominant
symptom had a significantly worse outcome and a higher likelihood
of ischemic abnormalities on perfusion single-photon emission
computed tomography (SPECT) than those who had typical angina
pectoris or who were asymptomatic.
9 Di Carli and Hachamovitch
10 discussed the dilemma of screening for occult CAD among asymptomatic
diabetic patients and stressed the excellent yield of abnormal
SPECT findings in the setting of dyspnea. Exertional dyspnea,
however, is less specific for the diagnosis of ischemia in patients
with chronic kidney disease, as pointed out by Gupta and coworkers,
11 because it may be secondary to anemia, volume overload, and
several other factors associated with renal failure.
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Palpitations
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A patients subjective feeling of rapid heartbeat, sometimes
irregular, with a sense of trembling in the chest, experiencing
what we call palpitations, may not be recognized by the physician
as an indication of myocardial ischemia. This is despite the
well-known notion that ischemia is a significant harbinger of
cardiac arrhythmias, mainly of the ventricular variety,
12 especially
if a vasospastic mechanism is suspected to be the cause of silent
myocardial ischemia.
13 Ambulatory ECG monitoring has demonstrated
an increase in arrhythmias during transient ischemic episodes
14,15 and also that cardiac acceleration usually precedes and frequently
continues during a transient silent episode.
16 Tresch and Aronow
17 stressed that cardiac arrhythmia may be a manifestation of myocardial
ischemia in elderly patients. We know now that structural alterations
occur in the transiently ischemic myocardium.
18 Muscle fiber
hypertrophy and increased interstitial nonmuscular tissue develop,
especially in the endocardial layer, and the changed electrophysiological
properties of the myocardium create an arrhythmia-prone milieu
with life-threatening potential. Wit and coworkers
19 demonstrated
the marked influences of myocardial ischemia on the electrophysiological
properties of the myocardial cell. Although this association
between ischemia and arrhythmias appears obvious, there is no
documentation that the perception of transient rapid or irregular
heartbeats may be the sole expression of an otherwise silent
ischemic episode.
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Fatigue
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A patient may complain of a sudden limitation in the ability
to walk and of feeling "suddenly weak." Braunwald
20 considers
fatigue to be "among the most common symptoms in patients with
impaired cardiovascular function" and also "one of the most
nonspecific of all symptoms." He mentions, however, that fatigue
may be a "possible" symptom that may precede or accompany an
acute myocardial infarction. Thadani
21 pointed out that the
deterioration of the walking distance of a patient should call
the attention of the physician to ischemia if associated with
chest pain; without pain, however, this complaint will usually
point to the diagnosis of heart failure. Fatigue in diabetic
patients who are otherwise asymptomatic requires further testing
for CAD, according to the American Diabetes Association recommendations.
22 Despite the fact that coronary blood flow limitation that results
in myocardial ischemia is evidently a good reason to feel "weak,"
authoritative texts do not mention fatigue as a possible expression
of a transient ischemic episode.
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Erectile Dysfunction
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This symptom may be a potential marker to identify diabetic
patients who should be screened for silent CAD; the authors
of a study on this subject
23 also suggest that if silent CAD
is suspected in diabetic patients, especially if additional
cardiovascular risk factors are present, there is a need to
perform an exercise ECG before treatment for erectile dysfunction
is begun.
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Genetics
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Another important "sound" of harboring premature CAD may be
perceived from careful listening to the family history of a
person. A strong warning sign can be heard from the medical
history of a patients parents, and the warning is even
stronger if the doctor listens to the medical history of the
patients siblings. Nasir and coworkers
24 studied nearly
10 000 asymptomatic individuals, and the presence of premature
coronary disease in a parent was associated in males with a
64% prevalence of CAD and an even higher prevalence (78%) if
1 sibling had the premature disease. The corresponding figures
in females were 36% and 56%, respectively. This and other newly
gained information may be additional instruments for the family
risk score, applicable to population screening for identifying
families at risk who are possibly amenable to intervention.
25 One can only agree with ODonnell
26 that even if genome-wide
tests are available soon for genotyping or sequencing to identify
disease-associated genetic variants, an accurate family history
will likely still have an important role in clinical practice
for risk prediction and prevention.
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Guide for the Clinician
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As the Prevention V Conference emphasized,
2 risk assessment
begins in the physicians office. Whereas a patient may
misunderstand the cause and significance of a vague or ambiguous
cardiac sensation,
27 the ear of the physician should not miss
these "sounds" of ischemia, because this condition, if undiagnosed,
will certainly prolong the occult period of the disease, possibly
leading to serious consequences for the patient. Because many
new diagnostic procedures are available today to diagnose CAD,
they should be applied to a patient even in the absence of precordial
pain if other symptoms are potentially suggestive of ischemia.
These "sounds of silence" should be heard by us, even if they
are only "whispered." We should not miss using our advanced
diagnostic and therapeutic possibilities and should not let
silent ischemia "grow as cancer."
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Acknowledgments
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The author thanks Dr Golda Werman, Dr Robert Werman, and Liane
Herman for their excellent editorial help.
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