PATHOGENESIS

Vasospastic angina is caused by focal or diffuse spasm (of the smooth muscle layer of the arterial
wall) of a major coronary artery, resulting in a high-grade obstruction. Transient myocardial
ischemia causes angina in many patients; myocardial infarction may develop in some. Vascular
smooth muscle hyper-reactivity is thought to be central to the pathogenesis of vasospastic
angina.
Spasm may occur in the absence of any preceding increase in myocardial oxygen demand (eg,
exercise) and in normal or diseased vessels. It is usually focal in its anatomic distribution,
although spasm in more than one site and diffuse spasm have been described. Spasm can occur
in angiographically normal coronary vessels but more commonly at the site of atherosclerotic
plaques of variable severity.
RISK FACTORS AND TRIGGERS
Cigarette smoking is a major risk factor for vasospastic angina.
There is some evidence that genetic factors and insulin resistance are associated with
vasospastic angina.
Possible triggers include:
The use of multiple drugs including ephedrine-based products, cocaine, marijuana,
alcohol, butane, sumatriptan, and amphetamines
Guide wire or balloon dilatation at the time of percutaneous coronary intervention
Food-born botulism
Magnesium deficiency
EPIDEMIOLOGY
It appears to be more frequent in individuals from Japan compared to Caucasian populations.
The diagnosis is more often made in individuals less than 50 years of age than in older people.
CLINICAL PRESENTATION
Patients with vasospastic angina typically present with a chronic pattern of recurrent episodes of
chest pain. The quality of the chest pain is indistinguishable from classical angina pectoris
associated with obstructive coronary artery disease; however, the context in which it occurs
differs. In particular, patients with vasospastic angina report that their episodes are
predominantly at rest and that many occur from midnight to early morning. Each episode of
chest pain generally lasts 5 to 15 minutes but episodes may last longer in some cases that are
refractory to initial medical therapy.

Discomfort is more often given as a descriptor than pain. Other common descriptors
include squeezing, tightness, pressure, constriction, strangling, burning, heart burn,
fullness in the chest, a band-like sensation, knot in the center of the chest, lump in the
throat, ache, and heavy weight on chest.
Each episode is typically gradual in onset and offset.
There is no change in the quality of pain with respiration or position.
The patient may have some difficulty in describing the location of the pain, although the
sub-sternal location is common. Radiation to the neck, throat, lower jaw, teeth, upper
extremity, or shoulder is common.
During each episode, symptoms of nausea, sweating, dizziness, dyspnea, and palpitations
may be present.
During an episode, tachycardia, hypertension, diaphoresis, and a gallop rhythm may be
present.

Bradycardia and hypotension can be observed if the sinus nodal, atrioventricular nodal,
and right ventricular arteries are involved during proximal right coronary artery
vasospasm.
Patients with vasospastic angina are often younger and exhibit fewer classic
cardiovascular risk factors (except for cigarette smoking)
A history of drug abuse (such as cocaine) may be present.
Hyperventilation can precipitate attacks of vasospastic angina.
Exercise does not usually provoke an episode of spasm.
ECG may reveal transient ST-segment elevation or depression in multiple leads.

DIAGNOSTIC
(1) nitrate-responsive angina,
(2) transient ischemic electrocardiographic (ECG) changes, and
(3) angiographic evidence of coronary artery spasm.
The diagnosis of vasospastic angina is made when a patient with recurrent episodes of anginal
type chest pain, which generally occur at rest, is found to have transient ST-segment elevation
on an electrocardiogram at the time of an episode and subsequently found to not have high
grade coronary stenosis at coronary arteriography.
In patients with a documented spontaneous episode, the diagnosis can be made on the basis of
nitrate-responsive angina with associated transient ECG changes.
During provocation testing, the diagnosis of vasospastic angina is confirmed if the provocative
stimulus induced chest pain, transient ECG changes, and a >90 percent constrictor response.
12-lead ECG Transient (less than 15 minutes) ischemic ST changes in multiple leads of a 12lead ECG are usually seen during an episode of chest discomfort. Unlike most other causes of
chest pain and ischemic ST changes, the ST-segment returns to baseline rapidly upon resolution
of symptoms. Occasionally, a transient period of T wave inversion may be seen before return of
the ECG to baseline.

In most cases, troponin values are in the normal range in patients with vasospastic angina,
due to the relatively short duration of myocardial ischemia.
In one report using 24-hour ambulatory ECG monitoring, 79 percent of episodes were
asymptomatic.
In one study of over 1000 episodes in 240 patients, 92 percent of ischemic episodes were
asymptomatic.
Stress testing - many patients with anginal chest pain and no transient ischemic STsegment changes should undergo some form of stress testing to screen for significant
fixed coronary artery disease.
Coronary arteriography is recommend

DIFFERENTIAL DIAGNOSIS
The diagnoses most often confused with vasospastic angina when ST-segment elevation is seen
include acute ST-elevation myocardial infarction (STEMI), acute pericarditis (with or without
myocardial involvement), stress-induced cardiomyopathy, and non-cardiac chest pain associated
with early repolarization.
Characteristics that separate these diagnoses from vasospastic angina include:

In patients with STEMI, pain and ST-elevation are usually present for more than 15
minutes. Acute therapy with nitroglycerin or calcium channel blocker does not usually
resolve symptoms and ST-elevation.
Acute pericarditis and stress-induced cardiomyopathy are characterized by pain that has
been present for hours or days before presentation, as opposed to vasospastic angina in
which the episode of pain is much shorter and in which there is often a history of repetitive
episodes over a period of weeks or months. In patients with pericarditis, the chest pain is
often dissimilar to that of angina, with individuals often complaining of sharp pain that is
affected by position or breathing. Echocardiography is often abnormal in these individuals.
Non-cardiac chest pain associated with early repolarization generally occurs in patients
without classic angina pectoris and in whom the ST-elevation is chronic.

MANAGEMENT
Sublingual nitroglycerin is effective in reducing the duration of each episode. We recommend
that patients use sublingual nitroglycerin with the onset of each episode, both to decrease the
duration of symptoms and ischemia.
Lifestyle factors As smoking cessation removes one of the triggers for vasospastic angina and
leads to a significant decrease in the frequency of episodes, at least in the short term, smoking
cessation should be encouraged
Nitrates and calcium channel blockers Calcium channel blockers (nifedipine, diltiazem, and
verapamil) are the first-line therapy for vasospastic angina. These agents prevent
vasoconstriction and promote vasodilation in the coronary vasculature, thereby alleviating
symptoms. We often start with diltiazem at a dose of 240 to 360 mg per day
The long-acting nitrates are also effective in alleviating symptoms, but the occurrence of nitrate
tolerance makes them a less desirable first-line approach. For patients who do not have
acceptable improvement in symptoms on calcium channel blocker therapy, we add a long-acting
nitrate (eg, isosorbide mononitrate 30 or 60 mg once daily).
Rho kinase inhibitors Fasudil is a rho kinase inhibitor that has been shown to inhibit
acetylcholine-induced spasm.
Statins Statins have been shown to be effective in preventing coronary spasm and may exert
their benefits via endothelial nitric oxide or direct effects on the vascular smooth muscle.
Percutaneous coronary intervention Percutaneous coronary intervention (PCI) is not routinely
indicated for patients with focal spasm and minimal obstructive disease. However, PCI may be
helpful if significant obstructive coronary disease is present and thought to be a potential trigger
for focal spasm. Results are variable in this setting and depend, in part, upon the severity of the
fixed obstruction. Coronary artery stenting may be an effective therapy for selected patients with
medically refractory vasospasm that is associated with mild to moderate coronary disease and in
whom the vasospastic segment can be clearly identified.
Concerns about specific drugs

Nonselective beta blockers, such as propranolol can exacerbate vasospasm and should be
avoided.
Aspirin should be used with caution and at low doses, as it is an inhibitor of prostacyclin
production at high doses. However, for patients with atherosclerotic cardiovascular
disease, we give aspirin 75 to 81 mg daily.
Oral sumatriptan is used to treat acute migraine headache. However, its use has been
associated with coronary vasospasm and myocardial infarction.
Fluorouracil has been described to induce coronary artery spasm.

COMPLICATIONS
Myocardial infarction and life-threatening arrhythmias may occur in approximately 25 percent of
untreated patients with vasospastic angina.
For patients with sudden cardiac arrest and vasospastic angina, we often suggest placement of
an ICD, since it is often difficult to prove that the coronary vasospasm predated or was the
trigger for the arrest.
PROGNOSIS
In general, the long-term prognosis of patients with vasospastic angina is good, particularly in
patients receiving medical therapy. Survival at five years may be as high as 94 percent.