angina, microvascular angina, coronary vasculature

1. Dr Rikesh Tamrakar

3. Introduction
 Described as "A variant form of angina pectoris" by Dr. Myron
Prinzmetal in 1959
 Prinzmetal Angina
 Variant angina(specific form of vasospastic angina,)
 Episodes of angina pectoris, usually at rest and often between
midnight and early morning, in association with ischemic changes on
the ECG
 Episodes are triggered by coronary artery vasospasm in the absence
of high grade coronary artery stenosis

4. Population at Risk
 Associated with other vasospastic disorders like Raynauds, or migraine
headaches
 Patients with cocaine abuse, smoking, insulin resistance, Food-born botulism,
Magnesium deficiency
 Hyperventilation can precipitate
 Younger patient population (age < 50)
 More common in women with normal coronaries and in men with organic
lesions
 More frequent in Japan compared to white (Japan: up to 29%,France: 12% US
4%)

5. Pathogenesis
 Focal spasm of a major coronary artery
 Transient myocardial ischemia causes angina any patients. MI may
develop in some pts
 Vascular smooth muscle hyper-reactivity is thought to be central to the
pathogenesis of variant angina
 Spasm occurs in the absence of any preceding increase in myocardial
oxygen demand & in normal or diseased vessels
 Spasm is usually focal. Spasm in more than one site and diffuse spasm
have been described

6. Pathogenesis
 Vascular smooth muscle hyper-reactivity is a key factor in
the pathogenesis of coronary artery spasm
 Multiple receptors have been involved :
 acetylcholine, serotonin, histamine, noradrenaline, and
dopamine
 Increased calcium sensitivity of the vascular myosin
light chain mediated by
 enhanced Rho kinase activity
 and enhanced phospholipase C activity

7. Pathogenesis
 Autonomic nervous system —imbalance of vagal and
sympathetic tone in triggering coronary spasm
 Episodes of variant angina occur more often from midnight to
early morning (when vagal tone is higher)
 Endothelial dysfunction —may be a predisposing factor
 Associated microvascular dysfunction

8. Clinical presentation
 Chronic pattern of recurrent episodes of chest pain
 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
 Physical examination- no characteristic finding.
 However, during an episode, tachycardia, hypertension,
diaphoresis, and a gallop rhythm may be present

9. Investigations
 12 lead ECG is usually normal between anginal episodes
 The ST-changes returns to baseline rapidly upon resolution of symptoms.
Occasionally, a transient period of T wave inversion may be seen
 Other reported ECG abnormalities include a tall and broad R wave,
disappearance of the S wave, a taller T wave, and negative U waves
 Ambulatory ECG monitoring – help in the diagnosis, assess the efficacy of
therapy

10. Diagnostic criteria
COVADIS, Coronary Vasomotion Disorders International Study Group

11. Investigations
 Role of stress testing
 Angina and no ST-segment elevation should undergo stress testing
 Most will have a normal noninvasive stress test
 Exercise-induced spasm with ST-segment elevation- 10 to 30%
 Stress echocardiography with ergonovine provocation not
recommend now
 Role of coronary arteriography
 In suspected patients ,severe fixed obstruction needs to be
excluded
 Reasonable to refer a patient with a strong consitant history and
-ve ambulatory ECG monitoring.

12. Investigations
 Three provocative tests- done only when the diagnosis of
VA is suspected, but not firmly established
1. Ergonovine
2. Acetylcholine
 Associated with a low frequency of serious complications
(0.6 %) It is preferred to either ergonovine or
hyperventilation, by some
3. Hyperventilation
 A high specificity (100 percent) & a sensitivity of 55 to 95%

13. Treatment
 Reduces the frequency of symptomatic episodes and appears to
decrease the frequency of serious complications
 Smoking cessation - significant decrease in the frequency of
episodes
 Sublingual nitroglycerin decrease the duration of symptoms and
ischemia

14. Treatment
 Nitrates and CCBs(nifedipine, diltiazem, verapamil, amlodipine)
 effective and both prevent vasoconstriction and promote
vasodilation
 no studies comparing one therapy to another
 In one study the use of a calcium channel blocker therapy was an
independent predictor of myocardial infarct-free survival in VA
patients ( Ref
 Guanethidine and clonidine - not well studied in this setting

15. Treatment
 Rho kinase inhibitors – Fasudil, shown to inhibit acetylcholine-
induced spasm
 Statins - Effective in preventing coronary spasm and may exert their
benefits via endothelial nitric oxide or direct effects on the vascular
smooth muscle
 Magnesium – exhibited coronary vasodilation

16. Treatment
 Percutaneous coronary intervention - may be helpful if
significant obstructive CAD is present and thought to be a
potential trigger for focal spasm
 Effective medical therapy, such as calcium channel blockers,
should be continued after percutaneous revascularization

17. Treatment
 Concerns about specific drugs
 Nonselective beta blockers, such as propranolol should be
avoided
 Aspirin should be used with caution and at low doses, if needed
 All medications of the triptan class should be avoided
 5-Fluorouracil induce coronary artery spasm

18. Complications
 Myocardial infarction and life-threatening arrhythmias
upto 25 percent of untreated patients
 Myocardial infarction - usually due to concurrent
obstructive CAD
 With variant angina alone, coronary vasospasm may trigger
thrombus formation
 Lipoprotein(a) may play a role in this setting.
• interferes with fibrinolysis

19. Complications
 Arrhythmias - may be life-threatening
 type of arrhythmia is determined in part by the vessel & territory
involved
 Heart block - RCA,
 Vent Tachy- LAD
 The optimal approach with vasospastic angina & SCD is unknown.
 In an observational study of 23 patients with VA in whom an ICD was
placed for a documented ventricular arrhythmia
 all patients were alive during a median follow-up of 2.1 yrs (4 VF & 1
pulseless electrical activity)

20. Prognosis
 Infarct-free survival at 10 - over 80 percent
 Independent predictors of infarct-free survival include
 Extent and severity of CAD
 SVD has 99 and 94% survival at 1 and 5 year
 MVD has 87 and 77% survival at 1 and 5 year
 Use of calcium channel blockers
 Patients with a positive initial response to CCB are twice as likely to
have an event free clinical course compared to those with a poor
response initially
 Arrhythmic complication

23. Introduction
 First described by Kemp in 1973
 Cardiac syndrome X
 It has three characteristic features
1. Angina or angina-like chest pain with exertion
2. ST segment depression on treadmill exercise testing
3. Absence of obstructive CAD , with no spontaneous or inducible
epicardial coronary artery spasm on ergonovine or acetylcholine
provocation

24. Pathogenetic mechanisms
1. Structural alterations
2. Luminal obstruction
3. Vascular wall infiltration
4. Vascular remodelling/ Vascular rarefaction
5. Perivascular fibrosis
6. Functional Alterations
7. Endothelial dysfunction
8. Dysfunction of smooth muscle cells
9. Extramural compression
10.Reduction in diastolic perfusion

25. Clinical characteristics
 More common in women than men
 Typically younger than those with angina due to CAD
(mean age 49±9 Yrs. in two series)
 Chest pain is similar to angina-like pain in 50%
 The pain may be precipitated by effort, but also occurs at
rest

27. Clinical characteristics
 Duration of anginal-type chest pain is often prolonged.
 In a review of 99 patients the average duration of
chest pain
 more than 10 mts in 53 %
 more than 30 minutes in 35%.
 Many did not respond to S/L nitrates
 A strong association with psychiatric disorders such as panic
anxiety is observed
 Rheumatologic disorders, such as fibromyalgia and
costochondritis, and noncardiac causes of chest pain, such as
esophageal dysfunction, have occasionally been reported

28. Diagnosis
 Objective evidence of myocardial ischemia
 Usually effort-related anginal pain
 Exercise testing - Horizontal or downsloping ST segment
depression during exercise, as seen in patients with obstructive
CAD
 responds inconsistently to sublingual nitrates
 Ambulary ECG
 Diagnosis not considered until CAG rule out significant CAD
 Noncardiac cause must be considered

29. Diagnosis
Non invasive evaluation
 Exercise thallium-201 myocardial scintigraphy –
 may demonstrate regional myocardial perfusion defects during
exercise
 No perfusion defects nor RWMA after dobutamine or
transesophageal atrial pacing, despite the frequent
provocation of chest pain .
 ?ischemia is limited to the subendocardium
 CMR perfusion imaging - detect regional differences in
myocardial blood flow

30. Diagnosis
Additional invasive testing
 Measurement of Coronary Flow Reserve( CMR) : ratio of
maximal hypermic coronary blood flow to resting : < 2.5
diagnostic
 Coronary microvascular spasm: via intracoronary
Acetylcholine
positive response- Absence of epicardial spasm
- Reproduction of angina and ECG changes
 Intracoronary Adenosine to test Endothelium –independent
coronary microvasvular dysfunction

31. Prognosis
Patients with MVA may have
 poorer prognosis and more adverse events than general
population
 Independently associated with diastotic dysfunction and
hospitalization from HFpEF
 In subset of patients with MVA and ACS , outcome is not
benign but better than with a culprit coronay lesion
-PURSUIT trail

32. Treatment
 Aggressive risk factor modification
 Physical training
 Therapy is largely empiric and optimal therapy may vary with
mechanism of MVA
 Beta blockers -
 Most effective in reducing the frequency and severity of angina and
in improving exercise tolerance.
 No definite RCTs available
 Calcium channel blockers – effective mostly when mechanism
primary microvascular vasoconstriction

33. Treatment
 Nitrates – variable results
no benefit to Improvement with sublingual nitrates in about 40
percent of patients
 ACE inhibitors and statins – shows benifit
Small RCT
 assigned to treatment with either ramipril (10 mg OD) plus
atorvastatin (40 mg OD) or placebo .
 After six months, significant improvements in brachial artery flow-
mediated vasodilation (a marker of endothelial function), exercise
duration, and angina frequency compared to placebo
 Imipramine - Low dose imipramine, may be effective in some
patients

34. Treatment
 Ranolazine
 L-arginine
 Sildenafil- in resistant cases
 Hormone therapy –
 May be beneficial in postmenopausal women
 improving endothelium-dependent coronary vasomotion
 The Women's Health Initiative, mostly of primary prevention says
no

35.  Aspirin :
 No clear evidence but many of patients have multiple
cardiovascular risk factors , so reasonable to consider low dose
aspirin
 Statin: as usual indication
Treatment