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CARDIOLOGY CASEBOOK

A regular feature of the American Journal of Critical Care, Cardiology Casebook is intended to enhance practitioners’ knowledge
and critical thinking. Stylized case studies are accompanied by self-assessment quizzes. We welcome letters to the editors regarding
this feature.

PRINZMETAL’S ANGINA
By Kathryn Buchanan Keller, RN, PhD, and Louis Lemberg, MD. From Florida Atlantic University Christine
E. Lynn College of Nursing, Boca Raton, Florida (KBK) and the Division of Cardiology, Department of
Medicine, University of Miami School of Medicine, Miami, Fla (LL).

A 75-year-old female, retired private duty


nurse, has been complaining for the past 10
days of unprovoked classical attacks of
angina 2 to 3 a day usually in the mornings. The
angina occurs at rest and may last 5 to 10 minutes. On
cholesterol 1.19 mmol/L (46 mg/dL), low-density
lipoprotein cholesterol 2.46 mmol/L (95 mg/dL),
very-low-density lipoprotein cholesterol 0.31 mmol/L
(l2 mg/dL). A high-sensitivity C-reactive protein was
normal. A resting electrocardiogram (ECG) revealed
careful questioning she admitted to similar attacks a cardiac rate of 72/min, regular sinus rhythm, and
during the previous 2 years, which were disregarded was considered within normal limits (Figure 1). Since
because they were infrequent (every 4 to 6 weeks) the patient was asymptomatic and by history her new
and shorter in duration. However, the attacks were symptoms were unrelated to anything specific and
also unprovoked and unrelated to any specific activity, were in fact unprovoked, a 48-hour Holter ECG moni-
emotional upset, or food intake. Family history tor was applied in an effort to document any ECG
revealed her father and mother died at age 72 and 78, changes that may appear associated with her symp-
respectively, of causes unknown, and her only sibling, toms. A review of the Holter monitoring recording a
a brother, died at age 74 of an acute myocardial few days later revealed 2 episodes of unprovoked
infarction. Past medical history revealed symptomatic angina accompanied by marked ST-segment elevation
osteoarthritis of her large extremity joints. Periodically in the monitored leads that lasted 7 minutes. Occa-
she obtained relief with two 325 mg aspirin tablets 3 sional ventricular premature beats were noted during
to 4 times daily and lately had a greater dependency the attacks. The ST segments returned to normal after
on aspirin. In addition, she was taking a multivitamin 8 to 9 minutes in both episodes (Figure 2).
daily.
On physical examination, the patient was normal QUESTIONS
in weight 56 kg (125 lb), 1 m 65 (5 ft 5 in) in height 1. Which one of the following is the diagnosis in
and moderately active. Blood pressure was 120/75 this case?
mm Hg in the right arm, and pulse was 76/min and a. atherosclerotic heart disease
regular. The lungs were normal on auscultation. The b. congenital anomalous angina of the left
heart rate was 76/min; S1 and S2 were normal. A coronary artery from the right or non-
grade II aortic systolic murmur was heard over the coronary aortic sinus of valsalva
second right intercostal interspace, consistent with c. myocardial bridges
aortic valve sclerosis. The point of maximal cardiac d. Prinzmetal’s variant angina (PVA)
impulse was in the fifth intercostal interspace at the e. hypoplastic coronary arteries
midclavicular line. Peripheral vascular examination
was unremarkable. A complete blood count and uri- 2. Which of the following statement(s) is/are cor-
nalysis were normal. Blood chemistries revealed nor- rect?
mal liver and renal function. A lipid profile revealed: a. the occurrence of coronary spasm is
cholesterol 4.78 mmol/L (185 mg/dL), triglycerides referred to as PVA
1.35 mmol/L (120 mg/dL), high-density lipoprotein b. coronary vessel spasm is always associ-
ated with ST-segment elevation
To purchase reprints, contact Louis Lemberg, MD, University of Miami School c. PVA is a rare clinical phenomenon and
of Medicine, Division of Cardiology (D-39), PO Box 016960, Miami, FL 33101. has a benign course

350 AMERICAN JOURNAL OF CRITICAL CARE, July 2004, Volume 13, No. 4
Hewlett Packard 4755A
I aVR V1 V4

II aVL V2 V5

III aVF V3 V6

RHYTHM STRIP: II
25 mm/s; 1 cm/mV

LOC 00000-0000 40 00001

Figure 1 Routine resting electrocardiogram is within normal limits.

10:54:00-2

10:54:15-2

10:54:30-2

10:54:45-2

10:55:00-2

10:55:15-2

10:55:30-2

10:55:45-2

Figure 2 The clock times are given in hours, minutes and seconds. Arrows point to the ST-segment elevations. Note the regression
of “J” point elevation. Ventricular premature beats appear just before ventricular repolarization returns to normal. The subject’s
diary indicated that the acute electrocardiographic changes appeared at the time of the angina.

AMERICAN JOURNAL OF CRITICAL CARE, July 2004, Volume 13, No. 4 351
d. PVA may initiate serious cardiac arrhyth- e. PVA is unprovoked angina caused by
mias that can lead to sudden cardiac death coronary vasospasm occurring at rest,
(SCD) producing ST-segment elevations
e. PVA is unprovoked angina caused by
coronary vasospasm occurring at rest, Myron Prinzmetal first described a “variant” form
producing ST-segment elevations of angina in his classic 1959 publication in the Ameri-
can Journal of Medicine.1 The term “variant” angina
3. Which of the following statement(s) is/are cor- or PVA is a distinct clinical entity characterized by
rect? episodes of chest pain occurring at rest, associated
a. patients with PVA typically have the same with ST-segment elevation and caused by coronary
risk factors as patients with coronary vasospasm. Coronary vasospasm, however, is not syn-
artery disease onymous with PVA, since the clinical spectrum of
b. cigarette smoking is a risk factor for PVA vasospasm also includes angina associated with ST
c. PVA can be triggered by the use of cocaine depression and exertional angina. Variant angina rep-
d. PVA can be associated with Raynaud’s resents only 1 aspect of a continuous spectrum of
phenomenon acute myocardial ischemia caused by coronary vaso-
e. autonomic dysfunction has been impli- spasm.2 PVA, once thought to be infrequent, is cur-
cated in the etiology of PVA rently recognized more often and is a significant
f. angina attacks may vary with the men- determinant of cardiac morbidity and mortality. Con-
strual cycle tinuous 24-hour Holter ECG monitoring of patients
with PVA revealed serious cardiac arrhythmias in
4. The diagnosis of PVA is verified by which of approximately 50% of cases. These included complex
the following procedures? ventricular ectopic beats, ventricular tachycardia, ven-
a. echocardiography tricular fibrillation, asystole, and second- and third-
b. magnetic resonance imaging of coronary degree atrioventricular block.3 There was no relationship
arteries between the severity of coronary artery disease and
c. 24-hour Holter ECG monitoring the occurrence of these serious arrhythmias. In PVA,
d. event recorder these arrhythmias are generally associated with
e. ergonovine stimulation marked ST-segment elevation of 4 mm or more.4 Brad-
f. loop recorder yarrhythmias are associated with acute ST elevations
in the inferior leads, whereas ventricular arrhythmias
5. Which of the following is not/are not helpful in can be seen with acute ST elevations in the anterior
the diagnosis of PVA? leads.3 There is a high risk for SCD when ventricular
a. 24-hour Holter ECG monitoring arrhythmias occur during acute ST elevations; the
b. thallium-201 ECG exercise stress test ventricular arrhythmias during resolution of the ST
c. coronary angiography elevations (accelerated idioventricular beats) are
d. ergonovine stimulation benign and a sign of reperfusion.4,5 In a study of 114
e. event recorder patients with variant angina followed for 26 months,
SCD occurred in 42% of those who experienced seri-
6. Which of the following medications should be ous arrhythmias during their anginal episodes com-
used in the treatment of patients with PVA? pared with an incidence of 6% in those without
a. nitrates serious arrhythmias.4 Multivessel spasm increases the
b. calcium channel blockers risk of SCD.6
c. α-adrenoreceptor blockers
d. β-blockers 3. b. cigarette smoking is a risk factor for PVA
e. aspirin c. PVA can be triggered by the use of cocaine
d. PVA can be associated with Raynaud’s
phenomenon
ANSWERS e. autonomic dysfunction has been impli-
1. d. PVA cated in the etiology of PVA
2. d. PVA may initiate serious cardiac arrhyth- f. anginal attacks may vary with the men-
mias that can lead to SCD strual cycle

352 AMERICAN JOURNAL OF CRITICAL CARE, July 2004, Volume 13, No. 4
The classical clinical manifestation of PVA is recurrent episodes of ischemic chest pain occur at rest
chest pain at rest associated with ST-segment eleva- without the classic ECG manifestations of PVA (ie,
tion. PVA tends to occur in younger females who, ST-segment elevation) and normal or minimally
except for cigarette smoking, may not exhibit the abnormal coronary angiograms.
usual clinical cardiac risk factors.7 The anginal attacks
in PVA tend to have a circadian rhythm and generally 5. b. thallium-201 ECG exercise stress test
occur in the early morning hours.1,8 These attacks can c. coronary angiography
be triggered by alcohol, drinking iced drinks, rapid e. event recorder
eye movement sleep, ergonovine, atrial pacing,
cocaine, nicotine, acetylcholine, and hyperventilation.9 Exercise stress testing is of little use in the diag-
PVA has been associated with other vasospastic disor- nosis of PVA because the basic pathophysiology in
ders such as migraine headaches and Raynaud’s phe- PVA is a decrease in oxygen supply as a result of
nomena.10 vasospasm: this is in sharp contrast to the increase in
The pathogenesis of coronary spasm is not well demand with exercise that occurs in the pathophysiol-
understood. Factors implicated include the activation ogy of occlusive coronary artery disease. Coronary
of the autonomic nervous system (α-adrenergic recep- angiography in PVA often demonstrates normal coro-
tors) and endothelial dysfunction. Vasospasm can be nary vessels or minimal coronary artery disease (in
precipitated by acetylcholine and meta-choline and the elderly). An event recorder is patient reliant, and
prevented by atropine and α-receptor blockers, eg, as a result the recording may lack the onset or resolu-
prazosin or clonidine; these factors implicate involve- tion of the ECG recording during the angina in PVA.
ment of the parasympathetic nervous system and α- An event recorder is therefore not recommended for
adrenergic vascular receptors.11-13 Autonomic nervous the diagnosis of PVA.
system involvement is further supported by the obser-
vation that surgical sympathetic denervation has been 6. a. nitrates
effective in treating patients who are refractory to b. calcium channel blockers
medical treatment.14,15 The role of endothelial dysfunc- c. α-adrenoreceptor blockers
tion in PVA has been reported in a prospective study
of premenopausal women with variant angina in The nitrates and/or the calcium channel blockers
which endothelial dysfunction and the frequency of (nifedipine, diltiazem, or verapamil) are the mainstay
anginal attacks varied with the menstrual cycle and of treatment for PVA. Calcium channel blockers and
estradiol levels.16 Anginal episodes were most frequent nitrates prevent vasoconstriction and promote vasodila-
with the lowest estradiol levels and least frequent with tion. Prazosine is a selected α-adrenoreceptor blocker
the highest levels.16 Other studies have shown that the and is an alternative therapy in PVA. Long-term sur-
coronary artery that is vasospastic in PVA reveals dif- vival is excellent. β-Blockers can exacerbate vasospasm
fuse intimal thickening.17 This may be a response to in coronary vasospastic states and propranolol is
repeated spasms. known to prolong the attacks of PVA. β-Adrenergic
blockade of vasodilatory β-adrenergic receptors con-
4. c. 24-hour Holter ECG monitoring vert the effects of sympathetic stimulation into a pure
e. ergonovine stimulation α-adrenergic vasoconstrictor response. Thus the use
f. loop recorder of non-selective β-blockers should be avoided.19 Aspirin
in small doses (81 mg to 325 mg) block thromboxin
A 24- or 48-hour Holter recording can be very A 2 , a powerful vasoconstrictor, allowing the full
definitive in the diagnosis, but is dependent on attacks vasodilating and platelet-inhibiting effects of prosta-
of PVA. A loop recorder is an effective diagnostic cyclin. Aspirin in large doses inhibits prostacyclin
tool. The ECG recordings are stored at either a 7, 14, production.20 Excessive aspirin intake (325 mg tablets
21, or 42 minute event. Stored data can be retrieved at 4-8 daily) can aggravate coronary artery vasospasm in
any time. 18 Loop recorders can operate for 1 year PVA by blocking cyclooxygenase, which results in
before battery failure. suppression of prostaglandin production.
The most sensitive test for coronary artery spasm
is coronary stimulation by ergonovine, which has a SUMMARY
greater than 90% sensitivity and specificity for the Prinzmetal’s angina, often referred to as “variant”
diagnosis of PVA. This test is recommended when angina, is a temporary increase in coronary vascular

AMERICAN JOURNAL OF CRITICAL CARE, July 2004, Volume 13, No. 4 353
tone (vasospasm) causing a marked, but transient 5. Previtali M, Klersy C, Salerno JA, et al. Ventricular tachyarrhythmias in
Prinzmetal’s variant angina: clinical significance and relation to the degree
reduction in luminal diameter. This coronary vasospas- and time course of S-T segment elevation. Am J Cardiol. 1983;52:19-24.
tic state is usually focal at a single site and can occur 6. McAlpin N. Cardiac arrest and sudden unexpected death in variant angina:
complications of coronary vasospasm that can occur in the absence of
in either a normal or diseased vessel. Patients are pre- severe organic coronary stenosis. Am Heart J. 1993;125:1011-1015.
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nary spasm. Circulation. 1993;87:76-80.
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5th ed. Philadelphia, Pa: WB Saunders; 1996.
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are seen in those ECG leads that reflect the potential as a manifestation of alpha-adrenergic receptor-mediated coronary artery
variations of the epicardial surface of the left ventri- spasm: documentation by coronary angiography. Am Heart J. 1976;91:
148-152.
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primarily responsible for PVA. The diagnosis is made vasospasm in patients undergoing coronary arteriography with spasm
by observing transient ST-segment elevation during provocation test of acetylcholine. Am J Cardiol. 1999;83:1186-1191.
13. Lanza GA, Pedrotti P, Pasceri V, et al. Autonomic changes associated with
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induced symptom, but rather a supply (vasospastic) Cardiol. 1996;28:1249-1255.
abnormality, exercise treadmill stress testing is of no 14. Bertrand ME, Lablanche JM, Tilmant PY. Treatment of Prinzmetal’s variant
angina: role of medical treatment with nifedipine and surgical coronary revas-
value in the diagnosis of PVA. The most sensitive and cularization combined with plexectomy. Am J Cardiol. 1981;47:1375-1377.
specific test for PVA is the administration of ergonovine 15. Bertrand ME, Lablanche JM, Tilmant PY, et al. Complete denervation of
intravenously. Fifty micrograms at 5-minute intervals the heart (autotransplantation) for treatment of severe, refractory coronary
spasm. Am J Cardiol. 1981;47:1375-1380.
is given until a positive result or a maximum dose of 16. Kawano H, Motoyama T, Ohgushi M, et al. Menstrual cyclic variation of
400 µg has been administered. When positive, the myocardial ischemia in premenopausal women with variant angina. Ann
symptoms and associated ST-segment elevation Intern Med. 2001;135:977-980.
17. Miyao Y, Kugiyama K, Kawano H, et al. Diffuse intimal thickening of
should be present. Nitroglycerin rapidly reverses the coronary arteries in patients with coronary spastic angina. J Am Coll Car-
effects of ergonovine if refractory spasm occurs. diol. 2000;36:432-436.
Medical therapy classically employs vasodilator 18. Futterman LG, Lemberg L. A novel device in evaluating syncope. Am J
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