Clinical Sciences  Cardiology  Coronary Artery Disease

Introduction
Stable ischemic heart disease, coronary artery disease, and atherosclerosis We carefully distinguish between “angina” and “chest pain”—cardiac
of coronary arteries are all synonyms. They represent the progressive angina is often not human chest pain, and each patient will have their
growth of an atheromatic plaque (atheroma, lipid-laden plaque, lipid core anginal equivalent (see page 2).
with a fibrocollagenous cap) that induces the progressive narrowing of an
artery’s lumen. Once past critical stenosis (~ 70% obstructed), symptoms
will appear during times of increased demand, the heart beating faster and
harder, angina with exertion. This is called demand ischemia: symptoms
are provoked by increased exertion though the degree of stenosis remains
unchanged. The ischemia provokes symptoms. A reduction in the
demand (resting) relieves the ischemia, and thus the angina. The patient
experiences these things without a myocardial infarction, presents to the
clinic, and will not have symptoms at the time of presentation.

In this lesson, we discuss ischemic heart disease from the perspective of

slowly progressive stenosis of a coronary vessel. This information will
be relevant in the next lesson, where we discuss ischemic heart disease
from the perspective of the supply ischemia spectrum—unstable angina,
NSTEMI, and STEMI, collectively termed acute coronary syndrome,
referred to as the diagnosis myocardial infarction—where there is a
sudden and rapid occlusion of the already stenosed coronary artery
secondary to plaque rupture and thrombosis. The two states share the
same pathogenesis, treatment, and diagnostics—though we want to
build the story of chronic stable angina (this lesson) separately from
acute coronary syndrome (the next lesson).

We begin with the spectrum of disease, from chronic atherosclerotic plaque

progressively stenosing the vessel, through complete rupture and thrombosis.

The Spectrum of Coronary

When an angiogram is performed for another reason, luminal
Atherosclerosis = CAD = IHD irregularities are classified as obstructive vs nonobstructive.
Patients may have evidence of atherosclerosis but not know it. This is Obstructive means a compromise of >  50% stenosis and is not
asymptomatic ischemic heart disease.
synonymous with the 100% occlusion of rupture and thrombosis.
Stable angina is the presence of known IHD and demand ischemia, called
Stable Ischemic Heart Disease, SIHD. These patients have angina with
exertion. They will present outpatient, without elevation of the biomarkers
or ST segments, and will not be having angina at the time of the interview.

Unstable angina represents the nontotal occlusive form of rupture and

thrombosis. Cardiac enzymes will not be elevated and there will be no
ST segment changes. It is identified by angina at rest or provoked by
significantly less exertion.

NSTEMI, a non-ST-segment-elevation myocardial infarction, is also

a nonocclusive rupture and thrombosis. There are symptoms at rest and
the cardiac biomarkers are elevated, but the ECG will not demonstrate
ST-segment elevations.

STEMI, an ST-segment-elevation myocardial infarction, represents

the occlusive rupture and thrombosis of the atheroma, 100% occlusion
of the coronary vessel: transmural ischemia which will result in
transmural infarct if not intervened on. The patient will have angina
at rest, the biomarkers will eventually elevate if not elevated already,
and there will be ST-segment elevations in two or more anatomically
contiguous leads.

The urgency escalates from asymptomatic through STEMI, though

disposition is divided into outpatient (asymptomatic and stable),
inpatient (UA and NSTEMI), and cath lab (STEMI).

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Clinical Sciences  Cardiology  Coronary Artery Disease

What Is Angina = Clinical Reasoning 101

Angina means chest pain. Formerly, and because the first heavily studied
patient population was old veterans (old men), the classic illness script for
symptoms of myocardial ischemia were substernal chest pain radiating up
the jaw and down the left arm, in a patient who is cold, clammy, and with
a sense of impending doom. It is now known that there are many anginal
equivalents. Essentially any symptom, which OnlineMedEd presents in
the “associated symptoms” category, could be the only symptom. What
is most important is to know what the patient experienced during their
last ischemic event. Even though different arteries may be affected,
symptoms are usually the same in the same patient. The point is that
the symptoms are provoked when demand increases and are alleviated
when demand decreases. For that patient, stable angina symptoms will be
the same symptoms of a STEMI at rest. But if the patient is not already
known to have obstructive coronary artery disease, the only way to know
that the exertional symptom is truly that patient’s angina is to diagnose
that patient with coronary artery disease. You do that by combining all
the elements of the case—history, physical, risk factors, laboratories, and The path of clinical reasoning is the same for ischemic heart disease
imaging—before deciding on a diagnostic test. And which diagnostic test whether you use exertional chest pain, exertional chest tightness,
is chosen depends on the level of certainty of the diagnosis and the age exertional dyspnea, or exertional angina. Chest pain is not typical or
of the patient. Because this is the stable ischemic heart disease lesson, the atypical (Diamond-Forrester). Chest pain is not cardiac or noncardiac
atherosclerotic disease without rupture and thrombosis, the patient will (current American College of Cardiology guidelines). And considering
present without active symptoms, will not require acute diagnostics, and
that angina has equivalents, chest pain may not even be pain.
will not receive acute therapies.
Angina is a symptom, a singular component of a larger story which
Stable Angina = Stable Ischemic Heart ends in the diagnosis of coronary artery disease.
Disease = CAD
*We switch to chest pain—the symptom—and angina—the chest pain
Symptoms of chest pain are most likely to be angina if the patient has
had that symptom before, which was provoked by exertion and relieved
of myocardial ischemia—to be concrete. Know that the associated
by rest. Nitroglycerin is a venodilator that drops preload, reducing the symptoms could be the only symptoms and that patient’s angina
amount of work the heart must perform. Like rest, a decreased amount equivalent.
of work decreases the demand. A pain that improves with nitroglycerin
is more likely to be angina. For those familiar, this may sound like the Diamond-Forrester
classification of chest pain. However, Diamond-Forrester overlaps
Associated Symptoms. Common symptoms associated with the only in the concept that more myocardial oxygen demand makes the
chest pain of cardiac ischemia may be the only presenting symptom: angina worse, and less myocardial oxygen demand makes it better.
dyspnea, nausea and vomiting, and presyncope. If the chest pain and
the associated symptoms both respond to exertion and rest, the chances
of ischemia go up.

Risk Factors. The patient’s medical history influences the likelihood

of atherosclerosis. Nonmodifiable risk factors are a family history of
early infarction and age (45 and up for males, 55 and up for females).
Modifiable risk factors are the same as for atherosclerosis: hypertension,
dyslipidemia, obesity, smoking, diabetes, chronic kidney disease, and
atherosclerotic disease anywhere else (vasculopathy). The more of them,
the worse they are, the higher the risk.

Physical. The classic presentation of myocardial ischemia is chest pain

that is nontender, nonpositional, and nonpleuritic. However, because
chest pain is now no longer the only anginal equivalent, pain that is
tender, positional, and pleuritic only increases the probability of some
other cause, without reducing the probability of coronary ischemia.
The assumption is that, in this lesson, the patient presents with
Labs. Because they are not presenting with symptoms, a troponin-I and
a history of angina and not active symptoms. Even if it is a new
12-lead ECG are not necessary (though evidence of old infarcts on the
12-lead may be useful, there is no need to rule out a STEMI). Instead, the
diagnosis of CAD, if the patient presents with acute chest pain and is
patient must be interpreted as either low, intermediate, or high risk. Low- symptomatic, get a 12-lead ECG, and act as if the clinic is an urgent
risk patients should not receive testing. Intermediate-risk and high-risk care. For ease of communicating with you, we assume the patient in
patients get some form of noninvasive testing (anatomic or functional). this lesson is not actively symptomatic.
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Clinical Sciences  Cardiology  Coronary Artery Disease

Stress Testing and CCTA

If a patient has crossed the threshold—there is a high enough probability
of CAD that they need a diagnostic test—some diagnostic test is
performed. Because the patient does not have active symptoms and is
in the outpatient setting, the labs needed to diagnose acute coronary
syndrome are not needed here. The choice is between anatomical
testing with coronary CT angio (CCTA) and functional testing with a
stress test. There are more options, but these two illustrate the concepts.
CCTA is better at ruling out obstructive coronary artery disease, and,
when negative, carries a 2-year warranty against acute ischemic events.
CCTA is therefore best used in patients with nonobstructive lesions and
low chance of disease burden. As age is the single greatest risk factor
for atherosclerosis, choose CCTA to rule out younger patients (<  65
years old). Conversely, stress testing is more likely to positively diagnose
patients with obstructive disease and more likelihood of more disease
burden. For patients 65 and older, use a stress test.

A stress test involves some form of inducing increased myocardial

demand (stress) and evaluating the heart’s response to that demand
(test). Stress comes in the form of exercise or pharmacological induction.
Test can be a 12-lead ECG, echocardiogram, MRI, or nuclear scan.

The best test is an exercise treadmill 12-lead ECG. It is cheap, easy to

perform, and has no radiation exposure. The patient must be able to walk
on a treadmill as the stress, and endure a normal baseline 12-lead ECG
as the test. A positive test is the provocation of that patient’s angina and A negative exercise treadmill stress test says only that any atherosclerosis
ST-segment changes, both of which go away when the patient rests. has not reached critical stenosis. It does not rule out coronary artery
disease, only makes it very unlikely that there is a plaque nearing
Pharmacological induction could be via an increase in the heart rate
(dobutamine), induction of coronary steal (dipyramidole), or various
rupture and thrombosis.
other mechanisms you will not have to choose from. Use pharmacological
induction when the patient cannot walk.

Echocardiogram testing is used when the baseline 12-lead ECG is

abnormal but the ejection fraction is normal. It works on the premise
that dead things don’t move and ischemic myocardium acts like dead
tissue. At rest, healthy myocardium will contract and relax, while dead,
scarred tissue will not. With increased demand, at-risk tissue will
become ischemic and undergo myocardial stunning, and won’t move.
The area of the heart that contracted at rest, but does not move with
exertion is tissue that needs reperfusion, a positive test. Nuclear testing
is chosen when the 12-lead and the echo are both abnormal.

If any noninvasive test is positive, the patient goes to a confirmatory

invasive coronary angiogram, a left heart cath.
A negative nuclear stress test carries a 1-year warranty, as compared
Invasive Coronary Angiography (ICA) to the CCTA’s 2-year warranty, fitting with the concept that CCTA
ICA, left heart catheterization, angiography, and diagnostic cath are
rules out disease while a stress test rules in disease.
all synonyms. ICA is the insertion of a wire into an artery (radial or
femoral), the threading of that wire to the coronary ostia on the aortic
valve, and the injection of contrast dye into the coronary vessels.
The cardiologist watches in real time on a screen as the contrast fills
the vessels. Multiple views are obtained and contrast is injected into
each ostium. The objective is to identify the number and location of
obstructive lesions (> 50% stenosis), as well as the size of the artery
and how close to the ostia the lesion is. This information informs who
will treat, and how. For a small number of relatively small vessels that
are easily reached with a wire, an interventionalist will open the lesions
with angioplasty and stents. For a large number of vessels, or those that
are not easily reached, or a major proximal vessel, a surgeon will perform
a CABG. Only obstructive lesions should be corrected or bypassed.
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Clinical Sciences  Cardiology  Coronary Artery Disease

Percutaneous Coronary Intervention (PCI)

PCI, balloon angioplasty, stenting, and therapeutic cath are essentially All cardiologists are trained in ICA and can go to the coronary ostia.
synonyms. Via a guidewire, the interventionalist threads a balloon into But only an interventional cardiologist can enter the coronary arteries
the coronary ostium and to the site of a lesion. The balloon’s inflation with a wire—percutaneous coronary intervention (PCI).
smushes all the plaque-stuff into the wall of the artery, restoring the
lumen, which is confirmed by the absence of any stenosis after more
dye is injected. Inflation of the balloon is angioplasty—this restores the
lumen, but will not prevent the atheroma from reforming (the plaque-
stuff is still present after the balloon is removed). To keep the plaque-
stuff out of the lumen, a stent can be placed. A bare-metal stent (BMS),
a cage longer than the lesion, is left in place. Because the stent is foreign,
the immune system overgrows it as if it were an atheroma, essentially
recreating the stenosis caused by the plaque, called restenosis. This takes
time, but not as much time as the necrotic lipid core. To resist restenosis,
stents that counteract the immune system were created: drug-eluting
stents (DES).

In-stent thrombosis, essentially rupture and thrombosis because of the

stent, is prevented with antiplatelets: aspirin and the P2Y12 inhibitors.
When used together, they are called dual antiplatelet therapy (DAPT).
For BMS, DAPT is required for one month. For DES, DAPT is
required for one year. The benefit of preventing in-stent thrombosis
and the risk of bleeding are balanced on an individual basis. If there
DAPT after 1 year continues if no bleeding/risk of bleed.
is no bleeding and low risk for bleeding, continue DAPT beyond 12
months. DAPT can be discontinued before the 12 months if there is a
DAPT may be converted to monotherapy early if bleeding or bleeding
bleed or bleeding risk is high. DAPT to monotherapy with aspirin has risk. @6 mo to ASA, @3 mo to P2Y12.
been shown safe at 6 months, and DAPT to monotherapy with a P2Y12
shown safe at 3 months.

Coronary Artery Bypass Graft (CABG) Lite

CABG is covered in Subspecialty Surgery in greater detail. A CABG
is performed for multiple vessels or for one large important one. The
reason for that is the left internal mammary artery (LIMA) is used to
bypass the most important blockage. This requires only one anastomosis
and results in perfusion of that coronary vessel in systole, as opposed to
diastole. All other bypasses will be a saphenous vein graft harvested CAD MEDS
from one of the legs, connecting the proximal aorta to the coronary Aspirin 81 mg
artery distal to the obstruction. Even though there is no metal like with
Atorvastatin 40 mg, 80 mg
stents, DAPT is used after CABG as well. Statin
Rosuvastatin 20 mg, 40 mg

Medical Therapy for Stable Ischemic Heart Disease HR: Metoprolol

β-blocker
The lesion is corrected (by stent or bypass). Medical therapy is designed BP: Carvedilol
to treat the atherosclerosis with a statin, prevent rupture and thrombosis ACE/ARB Any work, use ARBs
with aspirin, and prevent ischemic injury and heart failure with Clopidogrel
β-blockers and ACE/ARBs. In cases of stent or bypass and with no
contraindications because of bleeding, DAPT (aspirin with a P2Y12 2PY12 Prasugrel
inhibitor) is added for life (or until bleed risk gets unacceptably high). Ticagrelor

A patient may continue to have angina, most often in lesions that For patients without a history of infarction and with a normal ejection
are not amenable to procedural correction. Thus, after maximizing fraction, β-blocker may be discontinued if there are no other indications.
the β-blocker and ACE/ARB, if exertional angina persists, use anti-
anginals. If the blood pressure remains elevated, the hypertension
medications that also provide anginal relief are the dihydropyridine ANTI-ANGIALS
calcium-channel blockers, such as amlodipine and the nitrate Dihydropyridine calcium-
Amlodipine
isosorbide mononitrate. The other nitrate, nitroglycerin, can be channel blocker
used on an as-needed schedule. The last-ditch effort medication—for Nitrates scheduled Isosorbide mononitrate
palliation of refractory disease only—is ranolazine.
Nitrates prn Nitroglycerin
Ranolazine Ranolazine when refractive

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