Non Atherosclerotic angina

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Non-atherosclerotic Angina
By Dr. Doha Rasheedy
Definition of angina and its types:
 Angina pectoris is derived from the Latin verb ‘angere’ meaning ‘to strangle’. (1) It is a pain or discomfort of cardiac
origin that occurs in the chest, epigastrium, mandible, or shoulder and triggered or aggravated by physical activity or
emotional stress and relieved by nitrates.(2) It is not related to respiration or position.(3)
 Angina may paradoxically be reduced with further exercise (walk-through angina) or on second exertion (warm-up
angina).(3)
 Angina equivalents include shortness of breath on exertion, epigastric discomfort, fatigue, or faintness. (4)
Traditional clinical classification of suspected anginal symptoms:(3)
Typical angina Meets the following three characteristics:
(i) Constricting discomfort in the front of the chest or in the neck, jaw, shoulder, or arm;
(ii) Precipitated by physical exertion;
(iii) Relieved by rest or nitrates within 5 min.
Atypical angina Meets two of these characteristics.
Non-anginal chest pain Meets only one or none of these characteristics.
Non anginal chest pain can be a presentation of different etiologies like esophageal spasm, gastroesophageal reflux
disease, musculo-skeletal conditions of the chest wall, pericarditis, pleurisy, or anxiety. (5)
 Stable angina: it induced by effort and relieved by rest, does not increase in frequency or severity, and is predictable
in nature. It is associated with ST segment depression on ECG.(4) It is classified into 4 grades according to the
Canadian Cardiovascular Society (CCS) Classifications of Angina:(6)
Grade I: Angina only with strenuous exertion.
Grade II: Angina with moderate exertion: Slight limitation of ordinary activity.
Grade III: Angina with mild exertion: Marked limitation of ordinary activity, such as walking 1 to 2 blocks or climbing one
flight of stairs.
Grade IV: Angina at rest.
Adapted from Campeau L. Grading of angina pectoris [letter]. Circulation. 1976;54:522–523.
 Unstable angina: it is a rest angina (usually lasting >20 minutes), new-onset severe angina (within the past month
and, at least grade III in severity), and increasing in severity and frequency.(7) Secondary unstable angina is due to
additional conditions in the presence of coronary stenosis, such as tachycardia, fever, thyrotoxicosis, anemia,
hypertension or hypotension.(7)
Braunwald Classification of Unstable Angina(8)
Severity
I New onset severe angina or increasing angina but no angina during rest
II Angina during rest within (2-30 days prior) subacute angina at rest
III Angina during rest within the preceding 48 hours acute angina at rest
Clinical situation
A Develops secondary to an extracardiac condition that worsens
myocardial ischemia
Secondary unstable angina
B Develops when no contributory extracardiac condition is present Primary unstable angina
C Develops within 2 weeks of acute myocardial infarction Post-myocardial infarction unstable
angina
Adapted from Hamm CW, Braunwald E: APACHE II: A classification of unstable angina revisited. Circulation 102:118–122, 2000.
Pathophysiology of angina:
 It occurs mainly due to supply/demand mismatch.
 It is most commonly attributed to epicardial atherosclerotic coronary artery disease (CAD). However; in about 20-
30% of patients undergoing coronary angiography, there is non- atherosclerotic epicardial coronary vessels. This non-
atherosclerotic angina is higher among women, (9) and associated with increased mortality, a higher rehospitalization
rate, and a poor quality of life as most cases are reassured and even discharged without further investigation or
treatment. (9–11)

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 The symptoms and signs of myocardial ischemia in the absence of CAD (coronary stenosis ≥50% of the vessel
diameter) are called INOCA (Ischemia with No Obstructive Coronary Artery disease).(12)
Causes of non-atherosclerotic angina:
Vasospastic angina ( variant angina)
Coronary artery embolism
Spontaneous coronary artery dissection
Microvascular dysfunction
Takotsubo cardiomyopathy
Vasculitis
Coronary vessels anomaly: (myocardial bridging, fistula, abnormal origin of coronary vessels, coronary artery ectasia / aneurysm)
Angina due to mismatch in supply and demand of oxygen ( severe anemia, severe aortic stenosis, uncontrolled hypertension,
pulmonary disease)
Coronary artery vasospasm(CAVS):(13,14)
 Coronary vasospasm is a heterogeneous phenomenon that can occur in patients with or without coronary
atherosclerosis, can be focal or diffuse, and can affect epicardial or microvasculature coronary arteries (presentation
ranging from stable angina to acute coronary syndrome and in some cases sudden cardiac death).
 More common in women <50 years.
 The mechanisms of CAVS may be due to impairment of parasympathetic activity, coronary vascular and
microvascular endothelial dysfunction, enhanced smooth muscle vasoconstriction, chronic inflammation, and
oxidative stressors.
 It is more common in Japanese population and in those with polymorphisms in paraoxonase 1, endothelial nitric oxide
synthase.
Triggers include:
1. Cigarette smoking, psychological stress, cold exposure, hyperventilation, migraine, alcohol consumption leading to
magnesium deficiency, stimulants (e.g., cocaine), chemotherapies (including 5-fluorouracil and capecitabine), and
ergots.
2. Kounis syndrome: the occurrence of acute coronary syndrome (ACS) in the setting of a mast-cell and platelet
mediated hypersensitivity, or allergic reaction. Common triggers include antibiotics (especially beta-lactams) and
insect bites, which together account for half of reported cases.
3. Infectious myocarditis has been implicated in the development of CAVS in patients with otherwise non-obstructive
coronary arteries. The underlying mechanism is believed to involve direct inflammatory and infectious interference
with endothelial function of the coronary arteries. Well documented etiologies include viral infections with parvovirus
B19, and HSV.
4. Catheter induced vasospasm.
Current gold standard diagnosis of CAVS:
 Pharmacological provocative testing via intracoronary injection of high-dose boluses of acetylcholine,
ergonovine, or methylergonovine.
 Non-pharmacological provocation with cold pressor test and hyperventilation.
Positive cases show a coronary vasospasm with transient > 90% occlusion of coronary arteries during coronary
angiography, or via abnormalities of ventricular wall motion on echocardiogram or reproduce chest pain with ECG
changes. That is reversed by intracoronary nitrates.
Diagnostic criteria for CAVS include: (15)
Angina responding to nitrates with at least one of rest angina, marked diurnal variation in exercise tolerance,
hyperventilation precipitating episodes, or calcium channel blockers (but not β-blockers) suppressing episodes.
With one of the following:
 Transient ischemic changes during spontaneous episodes including at least two contiguous leads with ST segment
elevations ≥ 0.1 mV, ST segment depressions ≥ 0.1 mV.
 Coronary artery spasm visualized either spontaneously or during provocative testing.

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A case of coronary artery vasospasm
documented by pharmacologic spasm
provocation test during invasive coronary
angiography: focal vasoconstriction (arrow, A)
resulting in total occlusion of proximal left
anterior descending coronary artery developed
with ergonovine injection (E2, A), which was
normalized with nitroglycerin administration
(N, B). (16)
Treatment:(13,14)
 Smoking cessation, stop offending drugs, avoid precipitating events.
 First line pharmacologic treatment is calcium channels blockers (CCBs), patients with persistent symptoms may
benefit from the addition of long-acting nitrates or nicorandil, which reduce the frequency of anginal symptoms.
Sublingual nitrates may be useful for relieving acute episodes of angina.
 Statins and angiotensin converting enzyme (ACE) inhibitors have shown efficacy in preventing CAVS episodes, and
should be considered in all patients presenting with CAVS. The use of magnesium and antioxidants (such as vitamin
C and E) have demonstrated efficacy in many patients.
 Endothelin receptor antagonist therapy has been associated with enhanced coronary endothelial function and may
represent a targeted therapeutic agent for patients with epicardial and microvascular endothelial dysfunction.
 Beta blockers (BBs), both selective and nonselective forms should be avoided in patients with CAVS. Aspirin in large
dose block vasodilator prostaglandin effect and induce spasm.
 When spontaneous, focal, severe or occlusive CAVS that is resistant to medical therapy, a mechanical approach with
percutaneous coronary intervention and stent implantation could be of interest, and has been evaluated in small series.
Nevertheless, maintenance of CCB and nitrate therapy should be continued after the procedure, as vasospasm might
occur at other sites.
 For Kounis syndrome, treatment should follow the general principles for ACS treatment protocol and should include
corticosteroids and antihistaminic drugs. Epinephrine, the drug of choice in patients with anaphylaxis, may aggravate
ischemia.
Coronary artery embolism: (17) (accounts for 3% of ACS)
Types:(17)
1. Direct coronary embolism: from thrombi in left- sided cardiac structures, including the atrium, ventricle, and valves
e.g. left- sided tumors (myxoma), or thrombi.
2. Paradoxical coronary embolism: results from thrombus, such as deep vein thrombosis, or foreign material from the
venous circulation crossing into the systemic circulation via a patent foramen ovale or septal defect.
3. Iatrogenic: secondary to the passage of surgical material, thrombus or air into the coronary arteries during an
intervention e.g. PCI, and valvuloplasty with inadequate procedural anticoagulation.
Risk factors: atrial fibrillation, hypercoagulable states, prosthetic valves, infective endocarditis, intracardiac thrombi, and
patent foramen ovale. (18)
Diagnosis:
 It is difficult to distinguish embolism from atherosclerotic disease on the basis of the clinical presentation alone.
 Diagnosis is based on angiography together with clinical suspicion in patients with risk factors.
 Angiographic presentation includes an abrupt (cutoff) occlusion of a coronary artery (multiple occlusions raise the
level of suspicion) with a generally normal appearance of the remaining coronary vessels with absent collateral
vessels to the occluded artery.
 Transthoracic and transesophageal echocardiography can detect the underlying condition, such as prosthetic valve
thrombosis, intracardiac thrombus, endocarditis, or patent foramen ovale.(18)
Management:(17)
1. Because it is difficult to clinically differentiate CA embolism from atherosclerotic disease, the initial management
is similar for both conditions including antiplatelet therapy and targeted reperfusion therapy.

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2. If a clinically significant thrombus burden is present, aspiration thrombectomy should be considered. This
procedure alone can restore adequate coronary flow, without additional intervention.
3. If indicated, angioplasty or stent placement should be considered, ensuring adequate procedural anticoagulation
and antiplatelet therapy.
4. Treatment of the underlying condition: (18) Anticoagulation therapy at therapeutic levels is mandatory in cases
of atrial fibrillation and intracardiac thrombi. Surgical intervention for paradoxical embolism, endocarditis,
tumors, and prosthetic valve thrombosis.
Spontaneous coronary artery dissection (SCAD):(17)
 SCAD is defined as a non-traumatic, non-iatrogenic, and or non-atherosclerotic separation of the coronary artery wall,
which creates a false lumen that may or may not be in continuity with the true lumen. It is a coronary arterial intima–
media dissection with formation of a false lumen leading to deeper intramural hematoma and luminal compression.
 The predominant mechanism of myocardial injury is coronary artery obstruction caused by an intramural hematoma
(IMH) or intimal disruption with thrombus formation in the true lumen at the site of dissection.
 It accounts for up to 35% of ACS in women aged <50 years (mean age between 48 and 53 years). It accounts for 4%
of all cases of ACS.
 It can be related to fibromuscular dysplasia, peripartum status and connective tissue diseases, such as Marfan
syndrome, vascular Ehlers–Danlos syndrome. Precipitating stressors include intense physical activities and intense
Valsalva-like activities (e.g. vaginal delivery, coughing, vomiting, bowel movement) especially in patients with
underlying predisposing arteriopathy.
Investigations:
 In coronary angiography, SCAD can appear as a classic double
lumen with contrast filling into the dissection plane.
 Intracoronary imaging with intravascular ultrasonography (IVUS) or
optical coherence tomography (OCT) can be useful in detecting the
presence of hematoma or intimal disruption.
 Cardiac CT angiography can be useful for screening cases with
fibromuscular dysplasia.
Treatment:
 In hemodynamically and clinically stable cases: conservative medical management is generally regarded as the best
initial approach (medical management includes antiplatelet therapy, β- blockade, and statins).
 Systemic anticoagulation with heparin can reduce thrombus burden but carries a risk of extending the intramural
hematoma and, therefore, should not be routinely used in SCAD unless there is another indication.
 In patients with occluded blood flow or worsening clinical status, hemodynamic instability, or left main
dissection: revascularization with percutaneous coronary intervention (PCI) (can be unsuccessful in 50% of cases,
stents may cause the dissection to progress to adjacent coronary segments) or CABG surgery might need to be
considered (however, the patency of bypass grafts at follow up coronary angiography is very low).
 Conservative initial medical strategy in patients with stable SCAD, reserving coronary revascularization for patients
with ongoing or recurrent ischemia has been associated with an excellent clinical outcome. (19)
Takotsubo Cardiomyopathy (TTC): (18) (known as broken-heart syndrome, apical ballooning syndrome, and stress-
induced cardiomyopathy).
 It is a condition in which left ventricular (LV) dilatation and acute systolic heart failure occur, typically following an
emotional or physical stressor.

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 Ballooning of the LV occurs, most commonly in the apex (75-80%) or midventricle (10-20%). The most common
symptoms include chest pain (more than 75% of patients), dyspnea (50% of patients), and dizziness (more than 25%
of patients). Patients also may develop generalized weakness and occasionally syncope.
 Ventricular ballooning produces transient ST-segment elevation on ECG, increased levels of troponin and B-type
natriuretic protein (BNP), and a reduced ejection fraction resulting in acute reversible systolic heart failure.(20)
The name is derived from the centuries-old style of octopus
trap used in Japan to catch octopuses. This pot has a narrow
neck and a relatively wide base, allowing octopuses to enter but
not leave.(20)
 Up to 90 % of patients with TTC are postmenopausal women, it is characterized by transient systolic ventricular
dysfunction with regional wall motion abnormalities extending beyond a single vascular territory and in the absence
of significant obstruction in the epicardial coronary vessels.(18)
 Pathophysiology:(20,21) the exact pathophysiological mechanisms remain unclear but proposed mechanisms include:
multivessel epicardial spasm, microvascular dysfunction, catecholamines cardiotoxicity, and neurogenic stunned
myocardium., and possible role of estrogen (the increased prevalence of the syndrome in postmenopausal women
suggest possible role of hormones in the syndrome).
Revised Mayo Clinic criteria (4 criteria should be met)
 Transient left ventricular mid segments dyskinesia, with or without apical involvement; the regional wall-motion
abnormalities extend beyond a single epicardial vascular distribution, and a stressful trigger is often, but not always,
present.
 Absence of obstructive coronary disease or absence of angiographic evidence of acute plaque rupture.
 New ECG abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in the cardiac
troponin level.
 Absence of pheochromocytoma and myocarditis.
Treatment: is largely supportive and continues until the spontaneous return of left ventricular function (within 21 days
of the onset of the syndrome in 95% of cases).(22)
pulmonary
congestion
Venodilators (such as nitroglycerin, nitroprusside, or nesiritide) and Diuretics
In presence of hypertension (ACEis, ARBs, ARNI, spironolactone)
cardiogenic shock
urgent ECHO
with left ventricular
outflow tract obstruction
(LVOTO)
Avoid inotropes
IV fluids, Beta-blockers, if tolerated, to reduce basal contractility, Vasopressors
Extracorporeal membrane oxygenation (ECMO) may be necessary in severe
cases of cardiogenic shock with LVOTO
without obstruction Inotropes such as milrinone, dobutamine, and dopamine can be used.
Vasopressors and left ventricular assist devices for refractory cases.
Initiate anticoagulation if large area of hypokinesia.
Coronary Microvascular Dysfunction (CMD):(23) Coronary microvascular (vessels <0.5 mm diameter) dysfunction
can be detected in 30% to 50% of patients with chest discomfort and non-obstructive CAD on invasive coronary
angiography.
It is more commonly seen in women and patients with cardiovascular risk factors (e.g., increasing age, diabetes mellitus,
hypertension, smoking, or dyslipidemia). It is accelerated by early menopause and obesity.
Microvascular angina was previously identified as cardiac X syndrome which was characterized by the triad: symptoms of
ischemia, signs of ischemic ECG or stress tests and absence of obstructive coronary disease documented by the
angiography.
Classification and Pathogenesis: (24), (12)differ in different types

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Types of CMD Clinical setting pathogenesis
Primary
microvascular
angina
CMD in the absence of
myocardial diseases and
obstructive CAD
DM, HTN, dyslipidemia
present as microvascular angina
Endothelial dysfunction
Smooth muscle cell (SMC) dysfunction
Vascular remodeling
Secondary
microvascular
angina
CMD in myocardial diseases (hypertrophic cardiomyopathy,
dilated cardiomyopathy,
myocarditis, aortic stenosis and
infiltrative diseases)
Vascular remodeling
SMC dysfunction
Extramural compression
Luminal obstruction
CMD in obstructive CAD Stable angina
Acute coronary syndrome
Endothelial dysfunction
SMC dysfunction
Luminal obstruction
Iatrogenic CMD PCI
Coronary artery grafting
Luminal obstruction
Autonomic dysfunction
Altered coronary nociception is a possible contributing factor.
CMD in different myocardial diseases:(24)
 CMD can occur secondary to arterial remodeling, decreased capillary density, intimal hypertrophy along
with interstitial and perivascular fibrosis resulting from various cardiomyopathies e.g. hypertrophic
cardiomyopathy, dilated cardiomyopathy.
 Infiltrative cardiomyopathy: amyloidosis has the potential to cause CMD via three major mechanisms:
structural (amyloid deposition in the vessel wall causing wall thickening and luminal stenosis),
extravascular (extrinsic compression of the microvasculature from perivascular and interstitial amyloid
deposits), and functional (autonomic and endothelial dysfunction).(25)
 CMD in myocarditis: there is a causal relationship between parvovirus B19-related myocardial
inflammation and infection of vascular endothelial cells and CMD. Angina in patients with parvovirus
B19-associated myocarditis without significant CAD may be caused by intense coronary vasoconstriction,
as a result of myocarditis-induced coronary endothelial dysfunction and/or direct infection of endothelial
cells and/or smooth muscle cells.
CMD in aortic stenosis (AS):(26,27) AS induces a compensatory increase in left ventricular mass to counteract the
resistance to cardiac outflow. This increased left ventricular mass is associated with CMD which is caused by decreased
diastolic perfusion time, decrease resistance vessels per unit of weight (muscle hypertrophy not accompanied by increased
capillary density), and extramural compression by perivascular fibrosis.
 The study of myocardial blood flow (MBF), using positron emission tomography, has shown that MBF
increases proportionally with LV mass, despite reduced capillary density. Therefore it is conceivable that
the increase in resting MBF is due to metabolic vasodilatation in response to the increased oxygen
demand of LVH. This mechanism makes microcirculation unable to further increase blood flow,
contributing to limit CFR.
 Unlike HCM, coronary microcirculation in aortic stenosis does not develop structural changes like medial
hypertrophy or perivascular fibrosis.
Diagnosis is based on the presence of exertional ischemic chest discomfort, non-obstructive coronary arteries, and an
impaired coronary flow.
Impaired coronary flow can be determined during angiography by any of the following:
1. Coronary flow reserve <2.0 in response to vasodilator stimuli such as adenosine (endothelium independent).
2. Microvascular spasm diagnosed during provocative spasm testing, when chest discomfort and ischemic
electrocardiographic changes are induced by acetylcholine provocation in the absence of epicardial coronary
spasm (endothelium dependent).
3. Impaired coronary blood flow, this is also known as the coronary slow flow phenomenon, an angiographic
phenomenon that can occur spontaneously and is characterized as a delayed passage of angiographic contrast
[requiring ≥3 beats to fill a vessel] at rest.

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Non-invasive assessments for myocardial blood flow:(9)
1. Perfusion imaging by gadolinium-enhanced stress cardiac magnetic resonance.
2. Perfusion imaging with positron emission tomography.
3. Multislice detector computed tomography with an iodinated contrast.
The management options for CMD are limited, because revascularization therapies are not an option, and many
conventional antianginal vasodilator drugs are less effective on the microvasculature than on large epicardial vessels.
Among the conventional antianginal therapies, calcium channel blockers and β-blockers have been shown to be
beneficial in alleviating symptoms, whereas nitrates are less effective.
Other treatments:
1. Improving endothelial function (e.g., l-arginine, statin therapy, and enalapril).
2. Microvascular vasodilation: ranolazine and ivabradine.
3. Endothelin receptor antagonist therapy is a potential therapeutic under investigation.
4. Visceral analgesic effect (imipramine).
NB: COVID 19 is a microvascular disease:(28)
Pathophysiology of CMD in COVID-19 involves 5 pathways:
1. The disarrangement of local RAAS:
Angiotensin II elevation causes vasoconstriction, cellular hypertrophy, fibrosis, proliferation, and increased
ROS, it also triggers immune responses, promoting procoagulant and thrombotic states, and induces
endothelial cells expressing tissue factors and plasminogen activator inhibitor-1.
2. Cytokine storm is a systemic hyper-inflammatory and pro-thrombotic state.
3. Pneumonia/acute respiratory distress syndrome (ARDS)-elicited oxidative stress leading to endothelial dysfunction
(decreased nitric oxide release), and sympathetic overstimulation with increased coronary vasomotor tone.
4. Autonomic nerve dysfunction associated with mental, physical, or physiological factors alters coronary blood flow.
5. Reciprocity between the coronary microvascular endothelium and perivascular cellular structures due to viremia,
SARS CoV- 2 dissemination, and systemic inflammation:
 Compromised perivascular cells (i.e., myocytes, pericytes, and adipocytes), cause coronary microvascular
endothelial dysfunction. Pericytes or perivascular cells envelop the endothelial layers of microvessels in the body,
including the heart, and maintain the tone and integrity of microvasculature as well as promoting angiogenesis.
 Accordingly, a “COVID-19- pericyte hypothesis” was proposed: as the microvascular endothelial barrier is
damaged, SARS-CoV-2 leaks out and infects pericytes. This enhances VWF production in neighboring
endothelial cells and enhances platelet aggregation and fibrin deposition.
Congenital coronary artery anomalies (CCAAs):(29,30)
They are relatively uncommon <1% of general population; they are a common cause of sudden cardiac death among young athletes.
The clinical symptoms range from asymptomatic carrier, angina, dyspnea, palpitations, syncope, cardiomyopathy, arrhythmia,
myocardial infarction and sudden cardiac death.
Coronary CT is currently regarded as the diagnostic standard for the identification of CCAAs; other available tools include cardiac
magnetic resonance imaging (MRI), and invasive angiography (IA). The transesophageal echocardiography is accurate for the
identification of both the origin and the initial tract of CA.
They include anomalies of ostium, CA origin or termination, hypoplasia, duplication or absent CA. The anomalies with significant
risk include: ectopic origin of LCA from PA or the right sinus, ectopic origin of RCA form the PA or left sinus, coronary artery fistula,
and atresic or hypoplastic coronary artery.
a) The most severe congenital coronary origin anomalies in the adulthood are the origin of the left main of the
left coronary artery from the right aortic sinus, with a course between the aorta and the pulmonary trunk, and the
origin of the left main from the pulmonary trunk. Both can cause sudden death, usually associated with physical
exertion.

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Symptomatic cases have 3 treatment options: medical treatment/observation (namely β-blockers, calcium channel
blockers, nitrates, and antiarrhythmic drugs), avoiding severe exercise, and surgical repair with variable outcomes.
b) Coronary fistula (29–31)
It is a communication between the termination of a coronary artery or its branches and a cardiac chamber, a great vessel or
other vascular structure. Occur in 0.002% of the general population. Most instances of fistulae are congenital yet it can be
secondary to infective endocarditis, trauma of previous surgery, endomyocardial biopsy, coronary angioplasty and bypass
surgery, valve replacement, cardiac transplantation, or permanent pacemaker placement.
The vast majority of patients are asymptomatic. However, patients may become symptomatic, usually in the 5th
or
6th
decade of life, and may present with sudden cardiac death, myocardial ischemia, pulmonary hypertension, heart failure,
arrhythmia, or rupture.
Termination into a cardiac chamber or vascular structure with lower pressure may lead to enlargement and tortuosity of
the artery. Moreover, fistulae draining into right heart chambers function as left to right shunts and may result in RV
volume overload.
Coronary fistulae can cause ischemia by two possible mechanisms: First, there can be a steal of blood flow to the fistulous
tract from the normal coronary branches, leading to ischemia and rarely to infarction; and, second, there can be stenosis of
side branches secondary to thrombus associated with fistulous tracts, ulcerations and atherosclerosis.
Symptomatic patients with large fistulae should undergo closure of the fistulae at the drainage site by transcatheter
approach or surgical ligation. There is no consensus whether asymptomatic coronary fistulae should be treated or not.
c) Coronary artery ectasia/ aneurysm: (32)
Coronary artery aneurysm is a focal dilation of a coronary segment (≥1.5 times the adjacent normal segment),
while coronary artery ectasia is a more diffuse aneurysmal lesions. Both can be found in up to 5% of patients undergoing
coronary angiography. The right coronary artery is usually the most affected artery (40%) followed by the left anterior
descending (32%), and the left main being the least affected artery (3.5%).
Risk factors: genetic predisposition, atherosclerosis in 50% of cases, vasculitis e.g. Kawasaki, polyarteritis nodusa,
Takayasu, giant cell arteritis, connective tissue disease e.g. Marfan, and Ehler Danlos syndromes, local wall injury
following intracoronary manipulation (angioplasty, stenting), and mycotic aneurysm.
Coronary vasculitis causes four angiographically detectable coronary abnormalities: focal stenotic lesions, diffuse
narrowing, thrombosis, and late aneurysmal dilation.(33)
The vast majority of coronary artery aneurysm and coronary artery ectasia is detected incidentally during coronary
angiography or computed tomography. However local thrombosis in proximal large coronary artery aneurysms can lead to
distal embolization and acute myocardial infarction. Progressive enlargement of coronary artery aneurysm may result in
symptomatic local compression of adjacent structure (pulmonary artery, tricuspid valve, etc.) and can also eventually
rupture, producing life-threatening cardiac tamponade or fistulous communications.(32)
Angina due to microvascular dysfunction in dilated coronary arteries (dilated coronopathy) is documented in patients who
have coronary artery ectasia or coronary artery aneurysm without associated obstructive coronary lesions. (34)
Management: currently no guidelines to aneurysmal management. Atherosclerosis is implicated in the pathogenesis of a
large proportion of CAA especially in older patients; therefore, it is important to aggressively modify risk factors.
Lines of treatment depend on clinical presentations and may include: antiplatelet (dual), anticoagulants in multivessel
ectasia, and angiotensin-converting enzyme inhibitors that may slow the progression of CAA.
Vasodilators such as nitrates have been shown to exacerbate myocardial ischemia in patients with an isolated large
CAA, therefore their avoidance is recommended,
Percutaneous covered stent, coil embolization, or surgical excision may be considered.

9. 9
d) Myocardial bridging (MB): (35) Myocardial bridging is a congenital anomaly in which a segment of a coronary
artery takes a “tunneled” intramuscular course under a “bridge” of overlying myocardium. The most affected
region is the mid-segment of the left anterior descending artery.
The symptoms in MB depend on the length and thickness of the segment, the orientation of the MB in respect to the
surrounding myocardium and the presence of any adipose or connective tissue. In some patients it may have no
consequences, in others it causes vessel compression in systole, resulting in hemodynamic changes that may be associated
with angina, myocardial ischemia, acute coronary syndrome, left ventricular dysfunction, arrhythmias, and even sudden
cardiac death.
Atherosclerosis preferentially develops immediately proximal to the bridged segment, likely due to alterations in shear
stress, while the compressed segment itself is often spared.
Diagnosis: coronary computed tomography angiography, fractional flow reserve at baseline and with dobutamine
provocation, intracoronary Doppler, and intravascular ultrasound.
The invasive angiography reveals the classic finding of the phasic compression of the coronary artery during systole,
called “milking effect” .
First-line therapy of symptomatic bridging remains medical treatment with beta-blockers and non-dihydropyridine
calcium-channel blockers. Nitrates are contraindicated.
Surgical interventions include myotomy, intracoronary stenting (serious complications such as stent fracture, and
coronary perforation have been reported), and coronary artery bypass graft surgery have been used for refractory
symptoms, but long-term outcomes remain uncertain.
Coronary artery vasculitis: CAV (36, 37)
Vasculitis is a group of disorders characterized by inflammation of the blood vessels; it usually affects multiple organs
and therefore can have a myriad of presentations necessitating the need for a high index of clinical suspicion.
Vasculitis can be primary or secondary to another autoimmune disease (SLE, RA) or can be associated with other
precipitants such as drugs (hydralazine and penicillamine), infections (HBV, HCV, and COVID 19) or malignancy
(myeloma).
The most common causes of primary CAV include Polyarteritis Nodosa (PAN), Kawasaki’s Disease (KD), Takayasu’s
Arteritis (TA) and Giant Cell Arteritis (GCA). CAV leads to multiple complications including the development of
coronary artery aneurysms, coronary stenotic lesions, microvascular dysfunction, spontaneous dissection of large
coronaries, or thrombosis, all may result in acute coronary syndromes. Moreover it can manifest as pericarditis or
myocarditis.
Laboratory investigations include elevated inflammatory markers such as C-reactive protein, Erythrocyte Sedimentation
Rate, high sensitivity troponin assay and ANCA, Rheumatoid factor, Complement (C3 and C4).
Imaging modalities include cardiac magnetic resonance imaging, computed tomography coronary angiography,
fluorodeoxyglucose-positron emission tomography and conventional coronary angiogram with intravascular ultrasound.
Treatment:
1. All patients with known vasculitis should be treated with aspirin with needed immune-suppressive according to
the diagnosis.
2. Regarding revascularization techniques, percutaneous interventions are recommend in patients with either a single
vessel involvement or focal multivessel disease. While, CABG is recommended in these patients after induction
of immunosuppression. The involvement of the ascending aorta or the internal mammary artery may complicate
by-pass grafting. Scar healing might be compromised in patients with active disease.
3. Coronary artery aneurysms can be occluded by coiling or implantation of covered graft stents, even though the
risk of thrombosis and restenosis remains high. Aneurysm resection/thrombectomy and by-pass surgery can be
considered.
References:
1. Ford TJ, Berry C. Angina: contemporary diagnosis and management. Heart. 2020 Mar;106(5):387–98.
2. Cesar L, Ferreira J, Armaganijan D, Gowdak L, Mansur A, Bodanese L, et al. Guideline For Stable Coronary Artery Disease. Arq Bras Cardiol
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