Chronic Coronary Syndrome CCS Sisay.pptx

Chronic Coronary Syndrome
By Sisay Dadhi (IMR3)
Moderator: Dr. Seifu Baca (Internist , Cardiologist)
March, 2021

Outline
Introduction to CCS
Epidemiology
Pathophysiology of stable Angina Pectoris
Approach to patients with Angina/dyspnea and suspected CAD
Approach to Management
Angina without obstructive disease of epicardial artery
CCS in Specific circumstances

Introduction
The term stable CAD changed to CCS emphasizing the fact that the clinical
presentations of CAD can be categorized as either ACS or CCS
The spectrum of chronic coronary syndrome is broad and includes
 Coronary artery stenosis
 Prior MI/coronary revascularization &
 Asymptomatic ischemia
 Non-obstructive coronary disease
CCS is commonly caused by atheromatous plaque that obstructs or gradually narrow the
epicardial coronary arteries
Burden of IHD increasing even in LSE groups: Aging & ↑obesity and DM2

Pathobiological contributors of IHD
Not just epicardial stenosis!
Angina is a symptom for all cardiac ischemia regardless of the underlying mechanisms

Clinical Scenarios
oSuspected CAD and ‘stable’ angina symptoms, and/or dyspnea
oNew onset of HF or LV dysfunction and suspected CAD
oAsymptomatic/symptomatic patients <1yr after ACS or recent revascularization
oAsymptomatic/symptomatic >1 yr after initial diagnosis or revascularization
oThose with angina and suspected vasospastic or microvascular disease
oAsymptomatic subjects in whom CAD is detected at screening
All of these scenarios are classified as CCS but involve different risks
for future cardiovascular events(death or MI)

Epidemiology
It is estimated that 15.4 million Americans have IHD & 3.4 million aged ≥40 yrs have
angina pectoris
In 2013, IHD accounted for 46% of all deaths caused by CVD.
Despite decline in age-specific mortality over the past decades, IHD is the leading
cause of death worldwide.
WHO estimated by 2030, the global no of deaths from IHD will rise from 7.4 in 2012 to 9.2 million.
Lifetime risk for IHD
Major risk factors Men Women
Optimal 3.6% 1%
≥2 37.5% 18.3%

• A prospective cross-sectional, descriptive analysis done in Jan 2015
involving 6275 cardiac patients (6 referral hospital)

Stable Angina Pectoris
Results from myocardial ischemia w/c is caused by imbalance b/n
Myocardial O2 requirements
o Elevated with ↑ in HR , LV wall stress and contractility
Myocardial O2 supply
o Determined by coronary BF and arterial O2 content

Diagnostic and Management Approach: 6 Steps

Step 1: Symptoms and signs

History
Males constitute ~70% of all patients with angina pectoris
The typical patient with angina is a man >50yrs or a woman >60yrs
Typical angina described as heaviness/pressure/squeezing & rarely as frank pain
 typically lasts <10 min, and radiate to either shoulder and to both arms
 after exertion (exercise, sexual activity), heavy meal & waking up in morning
 relieved with rest or nitroglycerin, but may occur at rest
chest pain lasting for seconds is unlikely to be due to CAD
CVD symptoms or risk factors(family hx of CVD, dyslipidemia, DM, HTN, smoking)

Only 10- 15% of patients suspected of CAD present with typical angina!!!

Many patients report a fixed threshold for angina, which occurs predictably at a
certain level of activity, such as climbing two flights of stairs at a normal pace.
They are said to have Stable exertional Angina
Look for
Angina "Equivalents“ (dyspnea, syncope, fatigue, N/V)
Family hx of premature IHD (<55yr in 1st
degree M & <65yr in F relatives)

Angina as a “tip of an Iceberg!”

Canadian CV Society grading of angina pectoris

Physical Examination
Evidence of atherosclerotic disease at other sites, such as AAA, carotid bruits, and
diminished arterial pulses in the lower extremities
Evaluation for PAD should be done(ABI)
Examine the fundus
A 3rd
and/or 4th
heart sound, and, if previous infarction has impaired papillary muscle
function, an apical systolic murmur due to MR

Step 2: Comorbidities & other causes of symptoms
Before any testing considered, one must assess the patient’s general health,
comorbidities, and quality of life
If the pain is clearly non-anginal, other diagnostic testing may be indicated to
identify GI, pulmonary, or MSS causes of chest pain

Step 3: Basic testing
Basic testing in patients with suspected CAD
 laboratory biochemical testing
Resting ECG & CXR
possible ambulatory ECG monitoring
Resting Echocardiography

CBC, RFT, Lipid panel and DM2 screening in all patients suspected of CAD (Class I)
TFT in case of clinical suspicion of thyroid disorders

Biomarkers
Elevated troponin in CCS shown to have a graded relationship with the
subsequent risk of CV mortality and HF
 BNP increases in response to spontaneous or provoked ischemia
Though BNP/NT-pro BNP don’t have specificity to Dx CCS, higher values are
associated with risk for CV events in those at risk for & with established CAD

Resting & Ambulatory ECG
Normal in approximately 50% of patients with Hx of angina
Common abnormalities
nonspecific ST-T wave changes with or without abnormal Q waves
AV Conduction disturbances & LBBB
PVCs may occur, but have low sensitivity & specificity for detecting CAD
During angina episodes, abnormal ECG in 50% of cases who had normal ECG
Mostly STD
STE and normalization of resting STD or T-wave inversion may develop

Resting Echocardiography and MRI
Assessment of global LV function
RWM abnormalities is suggestive of CAD, whereas findings such as valve stenosis
or PHTN may suggest alternative diagnoses
↓ diastolic LV function reported to be early sign of ischemic myocardial
dysfunction and also be indicative of microvascular dysfunction
CMR provide information on cardiac anatomy and systolic function similar echo

Step 4: Ass’t of pre-test probability & clinical likelihood of CAD
The likelihood of obstructive CAD is influenced by the prevalence of the disease in the
population studied, as well as by clinical features of an individual patient
A simple model can be used to estimate PTP of obstructive CAD based on age, sex and
nature of symptoms
Studies have shown that outcomes in patients classified with the new PTP <15% is good
(annual risk of cardiovascular death or MI is <1%)
Diagnostic testing is most useful when the likelihood is intermediate

Different PTP scores
Diamond Forrester
Modified Diamond Forrester
CAD Consortium Basic & Clinical (Calculators)
Duke Clinical score
Acoustic CAD score
CAD Consortium Variables
Age
Sex
Chest pain
HTN
DM
Dyslipidemia
Smoking
CAC available? If available, CAC score

Low CVD risk population
PTP of Obstructive CAD in 15, 815 symptomatic patients: a pooled analysis
Classic Diomond Forrester + Dyspnea

For patients with PTP of 5-15%---PTP modifiers

Step 5: Selecting appropriate testing
If the diagnosis of CAD is uncertain, establishing a diagnosis using non-invasive
functional imaging before treatment is reasonable
Direct invasive angiography (ICA) without further testing is a reasonable option
high clinical likelihood of CAD with symptoms unresponsive to medical therapy
typical angina at a low level of exercise and
initial clinical evaluation indicating high event risk
Guidelines recommend the use of either non invasive functional or anatomical
imaging using CTA as the initial test for diagnosing CAD

Functional non-invasive tests
Designed to detect myocardial ischemia & include
Exercise ECG testing
Wall motion abnormalities by stress echocardiography/CMR
Perfusion imaging by single-photon emission CT (SPECT) or PET
Myocardial contrast echocardiography or Contrast CMR
Ischemia can be provoked by exercise/pharmacological stressors (↑myocardial
work load or O2 demand)

Anatomical non-invasive evaluation
Anatomical non-invasive evaluation, by visualizing artery lumen and wall using IV
contrast: coronary CTA
Either non-invasive or invasive functional testing is recommended for further
evaluation of stenosis detected by coronary CTA or ICA, unless a very high-grade
(>90%) stenosis is detected via invasive angiography

Physiologic response to Exercise

Exercise ECG
Exercise ECG has inferior diagnostic performance compared with imaging tests
In selected patients to complement clinical evaluation for the ass’t of response to
medical therapy, exercise capacity, suspected arrhythmias and event risk (Class I)
Considered as alternative to Dx obstructive CAD if imaging tests aren’t available
(Class IIb)
Baseline ECG abnormalities interfering with ECG interpretation
LBBB, paced rhythm, WPWp, STD >1 mm or (LVH/’Digoxin/Hypokalemia) with ST-T changes

Modified Bruce protocol add 2 initial low level 3-min stages at
speed of 1.7 mph and grades 0 % and 5%, respectively
HR, BP should be monitored & ST changes and symptoms followed

Exercise ECG testing in healthy individual
Variable Normal response
Peak Heart Rate response 85% of maximal predicted value or (at least 120– 140 bpm)
Blood pressure Increase
ST changes Normal or Rapid up-sloping
Heart rate Recovery(HRR) > 12 bpm after 1 min rest, > 18 bpm in supine/sitting position, >22 after
2 min rest
Symptoms No significant symptoms
Rhythm changes Infrequent PVCs can be seen

Indications for Terminating the Exercise Test

Stress MPI
Exercise or pharmacologic myocardial perfusion imaging (with SPECT/PET)
Exercise radionuclide MPI with simultaneous ECG recording is superior to
exercise ECG in
identifying MVD
localizing diseased vessel
determining the magnitude of ischemic and infarcted myocardium
Useful to DX CAD in those with abnormal resting ECGs & patients with
repolarization abnormalities caused by LV hypertrophy and digitalis

MPI with Pharmacologic Vasodilator Stress
For patients unable to exercise, especially elderly and those with PAD, pulmonary
disease, arthritis, orthopedic problems, severe obesity, or a previous stroke
Pharmacologic vasodilator stress with dipyridamole or adenosine

Stress Echocardiography
assess LV function in patients with chronic stable angina and patients with hx of
prior MI or clinical evidence of HF
2D echocardiography can assess both global and regional LV WMA that are
transient when due to ischemia
Stress (Exercise or dobutamine) may cause areas of akinesis or dyskinesis that are
not present at rest
More sensitive than exercise electrocardiography in the diagnosis of IHD

Stress CMR
Cardiac magnetic resonance (CMR) stress testing is also evolving as an alternative
to radionuclide, PET, or echocardiographic stress imaging
CMR stress testing with dobutamine can be used to assess RWMA accompanying
ischemia, as well as myocardial perfusion and viability

Cardiac CT
A noninvasive approach to imaging atherosclerosis and its consequences
Non-contrast CT is highly sensitive for detecting coronary calcification
Also provide angiography of coronary aa & quantification of ventricular function
CCTA is reasonable in symptomatic patients at intermediate risk, particularly, in those
with indeterminate stress testing
Has limited accuracy in those with uncontrolled tachycardia, heavy calcification, or in
the region of prior stenting

The impact of clinical likelihood on the selection of a diagnostic
test
Coronary CTA is the preferred test in patients with a lower clinical likelihood of
CAD, no previous diagnosis of CAD
The non-invasive functional tests for ischemia typically have better rule-in power
Functional non-invasive testing may be preferred in those at the higher end of
the range of clinical likelihood if revascularization is likely or the patient has
previously diagnosed CAD

Invasive testing
Invasive anatomical or functional(FFR) testing
ICA is only necessary when CAD is suspected & inconclusive non-invasive testing.
High clinical likelihood of CAD & symptoms unresponsive to medication or typical
angina at low level of exercise and initial clinical evaluation indicates a high event
risk, early ICA is reasonable to identify lesions amenable to revascularization
Integration of ICA with FFR has been shown to result in changes to the management
strategies of 30- 50% of patients undergoing elective ICA
The rate of major complications associated with routine femoral diagnostic
catheterization—mainly bleeding requiring blood transfusions—is still 0.5- 2%

Indications of ICA
Chronic stable angina severely symptomatic despite medical therapy
Patients with troublesome symptoms that present diagnostic difficulties in whom
there is a need to confirm or rule out the diagnosis of IHD
Patients with known or possible AP who have survived cardiac arrest
Repeatedly admitted for possible ACS

Angina in AS, HCMP
M >45 and F >55 years who will undergo cardiac surgery for any reason
Post MI if there is recurrence of angina, HF, frequent PVCs
If non-atherosclerotic cause of angina suspected
Chest discomfort suggestive of angina, but non-invasive tests are non-diagnostic

Findings
In patients with chronic stable angina
20% SVD
20% DVD
35% TVD
10% obstruction of the left main coronary artery
15%, no critical obstruction
Anatomically significant CAD is when luminal diameter narrowing is >70%

Limitations of Angiography
It is not a reliable indicator of the functional significance of stenosis
Underestimation of the severity and extent of atherosclerosis
Its inability to identify which coronary lesions can be considered to be at high
risk, or vulnerable, for future events, such as MI or sudden cardiac death
It is not helpful in predicting sites of subsequent plaque rupture or erosion

Advanced structural coronary imaging
Intravascular US:- vulnerability of coronary atheroma to rupture
Intravascular optical coherence tomography (OCT):- measures the fibrous cap
thickness and assess coronary dissection

Step 6: Assessment of event risk
Risk stratification identify those at high event risk who will benefit from
revascularization
All should undergo CV event risk stratification using clinical evaluation, LV
function with resting Echo and non-invasive ass’t of ischemia or coronary
anatomy
High event risk is defined as mortality rate >3%/year and low event risk <1%/year

Stress Testing Identifying High Risk Groups

Definitions of high event risk for different test modalities in established CCS

Management of CCS
Lifestyle modification: ↓ risk of subsequent CV events & mortality!!

Medical management
Comprehensive management of CCS has five aspects
Rx of associated diseases that can worsen angina and ischemia
Reduction of risk factors
Pharmacologic & non-pharmacologic interventions for secondary prevention
 Management of angina
Revascularization by PCI/CABG, when indicated
Aim: to reduce angina and exercise-induced ischemia& prevent CV events

Treatment of Associated Diseases
Several common medical conditions that can increase myocardial O2 demand or
reduce O2 delivery may contribute to the onset of new angina pectoris or
exacerbation of previously stable angina
Anemia, occult thyrotoxicosis, fever, infections and tachycardia

Treatment of Risk Factors
Search for & treat coronary risk factors
Hypertension
Diabetes mellitus
Weight loss in Obese
Cessation of smoking
Aggressive control of dyslipidemia

Anti-anginal drugs
Optimal treatment: controls symptoms and prevents cardiac events in CCS
Response to initial antianginal therapy should be reassessed after 2-4 wk Rx initiation
Nitrates
 Systemic venodilation + ↓LVEDP and volume…..reduce wall tension & O2 requirements
 Dilation of epicardial coronary vessels
 Increased blood flow in collateral vessels
LAN (nitroglycerin, isosorbide dinitrate) is 2nd
line Rx for angina when BB/non-DHP CCB is c/i or
insufficient to control symptoms (nitrate tolerance due to attenuation of vascular effect of nitrates)

Beta-blockers
Reduce oxygen demand by decreasing HR and myocardial contractility
The dose should be adjusted to limit the heart rate to 55-60
Abrupt withdrawal after prolonged use can result in increased total ischemic
activity in patients with chronic stable angina
Combination of a beta-blocker with a nitrate attenuates the reflex tachycardia
BB can reduce mortality & re-infarction after MI

44,708 patients
31% had prior MI
27% had documented CAD without
MI and
42% had CAD risk factors only
Primary outcome: composite of CV
death, nonfatal MI or nonfatal stroke

Published in 2014, Involving 15,603 patients
MI cohort….4772
CAD cohort…..7804
Only risk factors…..2101
Primary outcome: composite of the 1st
occurrence of
nonfatal MI, stroke or death from CV causes

Calcium channel blockers
CCBs improve symptoms, but have not been shown to reduce major morbidity or
mortality in patients with CCS
Verapamil has a large range of approved indications, including all varieties of
angina (effort, vasospastic, and unstable), SVT and HTN
Diltiazem(low-side effect) has advantages vs verapamil in the Rx of effort angina
Amlodipine + BB: additive effect on blood supply and myocardial O2 demands
Short-acting dihydropyridines be avoided b/c it can precipitate infarction,
particularly in the absence of concomitant BB therapy

Ivabradine
Is a specific and selective inhibitor of the If ion channel, the principal determinant
of the sino atrial node pacemaker current.
It reduces the spontaneous firing rate of sino atrial pacemaker cells and thus
slows the heart rate through a mechanism that is not associated with negative
inotropic effects.

Management of uncontrolled Angina
Despite conventional antianginal drugs & revascularization some patients
continue to have symptoms, many of whom are not a candidate for
revascularization
Unsuitable coronary anatomy (eg. diffuse CAD)
≥1 prior PCI/CABG
Lack of vascular conduits
Severely impaired LV function in those with prior PCI/CABG
Comorbidities that ↑ peri-/postop mortality (stroke, complicated DM & CKD)

Newer therapies for angina pectoris
Ranolazine….500-1000 mg po bid
Prevent both Ca2+ overload & subsequent increase in diastolic tension by Rapidly
inhibit Late inward Na+ channel
Also inhibit fatty acid oxidation(Switch to glucose oxidation)
its anti-ischemic effect is achieved without a meaningful change in HR/BP
↓angina frequency & nitroglycerin use when used with a BB or CCB
Study show statistically significant 0.3% reduction in HbA1c(pronounced in Diabetics)
Side effects: dizziness, nausea, constipation & dose-dependent QT prolongation

Trimetazidine
inhibit fatty acid metabolism and reduce the frequency of angina without hemodynamic effects
in patients with chronic stable angina
Trimetazidine (35mg b.i.d) + BB improved effort-induced myocardial ischemia
TRIMPOL II trial & a metanalysis: with other anti-anginal it was associated with
smaller weekly mean number of angina attacks
lower weekly nitroglycerin use
longer time to 1 mm ST-segment depression
longer exercise duration at peak exercise
Contraindicated in PD & other movement disorders

Nicorandil
Nicorandil (20mg po bid) dilates peripheral & coronary vessels acting on ATP-
sensitive K+ channels and possesses a nitrate moiety
mimic a natural process of ischemic preconditioning, protecting the heart from
subsequent ischemic attacks
Side effects include nausea/vomiting and severe oral & intestinal mucosal
ulcerations

Antithrombotic therapy in CCS
Antiplatelet drugs
Low-dose aspirin
irreversibly inhibit COX-1 and thus prevent thromboxane production
Current evidence supports 75 - 100 mg daily for the prevention of ischemic
events in CAD patients with or without a hx of MI

P2Y12 inhibitors
Block the platelet P2Y12 receptor, which plays a key role in platelet activation and
arterial thrombus formation
Clopidogrel & prasugrel: irreversibly block P2Y12 via active metabolites
Ticagrelor reversible P2Y12 inhibitor that doesn’t need metabolic activation

Options of DAPT combined with ASA in those with high/moderate risk of
ischemic events who don’t have high bleeding risk
High ischemic risk: diffuse MVD + one of the f/g: DM on drugs, recurrent MI, PAD
or CKD with eGFR <60
Moderate ischemic risk: at least one of the f/g: MVd/diffuse CAD, DM on drugs,
recurrent MI, PAD, HF, or CKD with eGFR <60

DAPT post-PCI
After PCI for stable angina, 6 months of DAPT achieves the optimum balance
of efficacy and safety in most patients.
Premature discontinuation of a P2Y12I is associated with increased risk of
stent thrombosis and is discouraged.
Shorter duration of DAPT be considered in those at high risk of life-
threatening bleeding in view of very-low risk of stent thrombosis after 1-3
months(DES)

Anticoagulant drugs in sinus rhythm
Combination of antiplatelet therapy and standard anticoagulant doses of warfarin
or apixaban for secondary prevention after ACS was associated with an
unfavorable balance of efficacy and bleeding (APPRAISE-2 trial)
Rivaroxaban 2.5 mg b.i.d vs Placebo ↓ the composite of MI, stroke/CV death in
stabilized patients treated predominantly with aspirin and clopidogrel following
ACS with increased bleeding risk (COMPASS & ATLAS-TIMI 51 trial)
Greater absolute RR seen in higher-risk pts with DM, PAD, moderate CKD & current
smokers

Antithrombotic in post-PCI patients with AF/other indication for OAC

Proton pump inhibitors
Proton pump inhibitors reduce the risk of GIB in those treated with antiplatelet.
PPI that inhibit CYP2C19 (omeprazole and esomeprazole) may reduce the
pharmacodynamic response to clopidogrel.

Statins and other lipid-lowering drugs
Goal: lower LDL-C <55 mg/dL or at least reduce by 50% from baseline

Role of colchicine
Despite widespread use of statin and antithrombotics patient with CAD continues
to be at risk of CV death, MI & need for revascularization
Pts with Hx of ACS remains at increased risk of recurrent CV events (20% at 3 years)
Partly due to residual inflammation at a culprit/non-culprit sites
Inflammation plays a central in atheroma generation, plaque instability & rupture
Endothelial injury trigerred by LDL lead to release of proinflammatory cytokines
w/c reduce plaque stability

Colchicine has an anti-inflammatory effect
Interfere with inflammasome w/c is
responsible for cytokines generation
Prevent cell mitosis
LoDoCo2 trial (2020)…0.5mg daily
Enroll 5,522 patients with the median ffp of
28.6 months
Inclusion criteria:
• CAD on invasive/CT angio
• CAC >400
• Clinically stable condition ≥6 months
Exclusion criteria:
GFR <30, Severe HF, Severe VHD
Primary endpoint: composite of cv death,
MI, ischemic stroke or revascularization
Result: reduce primary endpoint
significantly, shown statistically significant
reduction in risk of MI & revascularization
and borderline CV mortality benefit

RAS blockers
ACEI can reduce mortality, MI, stroke and HF among patients with LV dysfunction and
high-risk diabetes
should be given to CCS patients with HTN, EF 40% or DM unless contraindicated
ACEI Rx in CCS patients without HF or high CV risk is not generally recommended,
unless needed to meet BP targets (EUROPEAN, HOPE & PEACE trial)
Spironolactone/eplerenone: post-MI who are already on ACEI and BB, have EF 35% and
have either diabetes or HF

Revascularization
Revascularization plays a central role in the management of CCS on top of
medical Rx, but always as an adjunct without supplanting it
The two objectives of revascularization:-
Symptom relief in patients with angina and
Improvement of prognosis

Considered in the presence of
Unstable disease, Intractable symptoms, severe ischemia or high-risk
coronary anatomy, Diabetes & Impaired LV function
Other features, in addition to lesion severity, also influence likelihood of
success
Vessel size, extent of calcification, tortuosity & relationships to side branches

Medical therapy vs Revascularization???
5179 patients with moderate/severe
ischemia followed for 3.2 years
Initial invasive strategy (angio and revasc
when feasible + medical Rx) VS medical
therapy alone
Exclusion: EF < 35%, LM stenosis >50%,
anatomy unsuitable to PCI/CABG, non-
obstructive CAD, class III/IV HF
Primary endpoint: Composite of death
from CV causes, MI or hospitalization
for UA, HF or resuscitated cardiac
arrest
Secondary outcome was death from
CV causes or MI

RCT, enrolling 2287 patients over
median of 4.6 years
2/3 of patients had 2 or more vessel ds
Primary endpoint: a composite of
death from any cause and nonfatal MI
over the follow up year
Inclusion criteria: 70% stenosis in at least
one prox epicardial a & evidence of
ischemia (exercise/pharmacologic) or one
coronary stenosis of at least 80% and
classic angina without provocation
Exclusion criteria: persistent class IV
angina, shock, EF <30% and coronary
anatomy not suitable for PCI

What is an annual mortality with Medical therapy?

PCI- Indications
Persistent angina despite medical therapy, accompanied by evidence of ischemia on stress test
More effective than medical therapy for the relief of angina
Primary success: increase in lumen >20% to a residual obstruction <50% with relief of angina,
is achieved in >95% of cases
Recurrent stenosis occurs in ~20% of cases within 6 months of BMS
Angina recur within 6 months in 10% of cases

Those with at least one stenosis functionally significant (FFR ≤0.80) assigned to
FFR-guided PCI plus medical therapy vs medical therapy alone
The primary end point was a composite of death, MI or urgent revascularization
Recruitment was halted prematurely after enrollment of 1220 patients because
of a significant between-group difference in the percentage of patients who had a
primary endpoint event but no difference in risk of MI & death from any cause.

CABG
The technical goal of bypass surgery is to achieve, whenever possible, complete
revascularization of significant proximal stenosis.
It has been documented to prolong survival, relieve angina and improve QOL in
specific subgroups of patients with CAD (STICH trial)

Patient selection
The decision to perform PCI Vs CABG???
coronary anatomy
 LV function
comorbidities
risk associated with either revascularization and patient preference
SYNTAX, BARI 2D, FREEDOM trial
Heart Team

PCI VS CABG…..Angiographic Syntax Score

Syntax trial: 1800 patients with 3VD or LM CAD undergo CABG or PCI

Generally, CABG preferred
Left main
Three-vessel CAD
LV systolic dysfunction
DM patients

Patients with stabilized symptoms <1 year after an ACS or with recent revascularization
It is recommended that at least two visits in the first year of follow-up
In those who had LV syst dysfunction before the revascularization or after ACS,
reassessment of LV function must be considered 2- 3 months after intervention

Patients >1 year after initial diagnosis or revascularization
It may be beneficial to assess LV function, valve status and cardiac dimensions in
apparently asymptomatic patients every 3 - 5 years
In cases of unexplained reduction in systolic LV function, especially if RWMA,
imaging of coronary artery anatomy is recommended
It may be beneficial to assess non-invasively for silent ischemia in an apparently
asymptomatic patient every 3 – 5 years

Angina without obstructive epicardial CAD
Low diagnostic yield of ICA can be explained by the presence of
Mild/moderate stenosis or diffuse coronary narrowing, with under-estimated
functional significance
Disorders affecting microcirculation that escape the resolution of angiographic and
Dynamic stenosis of caused by coronary spasm that are not evident during CTA/ICA

Vasospastic Angina
Clinical entity characterized by episodes of rest angina that respond to short-acting
nitrates and attributable to coronary artery vasospasm
Patient commonly develop STE but sometimes STD can occur.
Usually occurs at sites of atherosclerosis but may occur within normal vessels.
Cigarette smoking is a major risk factor
Common triggers
drugs like cocaine, alcohol, sumatriptan and amphetamines
at the time of PCI
Food-born botulism
Mg deficiency

Pathogenesis
Poorly undestood
Vascular smooth muscle hyperreactivity
Autonomic Nervous system: imbalance of vagal tone(angina commonly from midnight-morning) &
sympathetic tone(enhanced alpha R stimulation)
Endothelial dysfunction(eg. Increased VC endothelin level)
Acetylcholine injection causes vasodilation in healthy arteries but vasoconstriction
ensues in atherosclerotic ones
Patient had heightened vasoconstrictor response to Ach & enhanced response to
vasodilator effects of nitrates.

Clinical presentation
Episodes of angina is typically gradual in onset and offset, lasting 5-15 minutes.
If prolonged it may cause MI
Can have associated sweating, palpitation or dizziness
Clues to differentiate from stable angina
Younger patient (<50 yr) with fewer CV risk factors
Other vasospastic disorders: Raynaud’s ds, Migraine
Hx of drug abuse
Exercise doesn’t usually provoke spasm(only 20% of pts develop STE by exercise test)

Diagnosis
History is very important
Transient ST segment changes during spontaneous episode and subsequently
found without high-grade obstruction on angiography
Ambulatory ECG monitoring……..Angiography

Coronary Artery Vasospastic Disorders Summit(COVADIS)
criteria

Treatment
Control of cardiovascular risk factors and lifestyle changes.
CCBs and long-acting nitrates are the treatment of choice
Nifedipine has been shown to be effective in reducing coronary spasm associated
with stent implantation

Microvascular angina(MVA)
Patients with MVA typically have exercise-related angina, evidence of ischemia on
non-invasive tests, and either no stenosis or mild-to-moderate stenosis (40-60%),
revealed by ICA/CTA, that are functionally non-relevant
Regional LV wall motion abnormalities rarely develop during exercise or stress in
patients with microvascular angina

Pathogenesis ……2 mechanisms
1) Microvascular dysfunction
Ischemia is limited to subendocardium
3 mechanisms
1. Endothelial dysfunction impaired microcirculatory conductance
2. Abnormal cardiac adnergic tone (arterial dysregulation)
↓VD or cause paradoxical VC in response to pharmacologic agents(adenosine, Ach) &
exercise Microvascular Spasm
This 2 process can involve bronchi or cerebral microcirculation
3. Occult small vessel CAD

2) Enhanced pain sensitivity
Can’t demonstrate ischemia evidence on exercise or dobutamine testing
Clinical feature
Chronic recurrent predominantly exertional angina & may occur from midnight to
early morning
Response to nitroglycerin may not be effective b/c its VD effect in small arteriole is
less
Diabetic & female at risk

Investigation
Resting ECG normal between episode and absent ECG changes during episode
can’t r/o
Unlike VSA, STE not a feature
Perfusion defects on MPI or RWMA on dobutamine Echo may be absent
Angiography should show normal epicardial aa( <30% stenosis)

Diagnosis
Hx + non-invasive testing + non-obstructive CAD
If this is inconclusive, measure CFR or index of microvascular resistance(IMR)
CFR = CBF with Adenosine/resting CBF (normal 2.5 - 5)
If there is no significant epicardial CAD, shows degree of resistance to BF in
microcirculation
Measured with Doppler wire or non invasively by echo(LAD flow) or PET
IMR is measured invasively with Doppler wire (catheter)
CFR <2 & IMR ≥25 indicates abnormal microcirculation function

Risk stratification
Presence of microcirculatory dysfunction in CCS entails a worse prognosis
Microcirculatory dysfunction precedes the development of epicardial lesions,
particularly in women is associated with impaired outcomes.
Diabetics without obstructive disease but with abnormal CFR have similarly poor
long-term prognosis as those with obstructive epicardial disease

Treatment
In those with abnormal CFR <2.0/IMR 25 units and a -ve Ach provocation test, BB,
ACE inhibitors, and statins, along with lifestyle changes are indicated
ECG changes and angina in response to Ach testing but without severe epicardial
VC (suggestive of microvascular spasm) may be treated like vasospastic angina

Specific circumstances
Hypertension
A recent Meta-analysis
suggests that for every 10
mmHg reduction in SBP,
CAD can be reduced by
17%

VHD(including Transcatheter AV implantation)

Diabetes mellitus
Diabetic patients had 2-fold increased risk of CAD
Patients with DM & CAD are considered to be at very high risk; so, LDL should be
lowered to <70 mg/d or by 50% if the baseline LDL is between 70 - 35 mg/dL
Target HgA1C is recommended to be <7%

Management of Refractory Angina
Refractory angina refers to long-lasting symptoms (3 months) in the presence of
obstructive CAD, which cannot be controlled by escalating medical therapy with
the use of second- and third-line pharmacological agents, CABG/PCI
Patients with refractory angina best treated in dedicated ‘angina clinics’ by MDTs
experienced in selecting the most suitable therapeutic based on an accurate
diagnosis of the mechanisms of the pain syndrome

Unconventional therapies for refractory Angina
Enhanced External counterpulsation(EECP)
is a technique that increases arterial blood pressure and retrograde aortic blood
flow during diastole (diastolic augmentation)
Cuffs are wrapped around the patient’s calves, thigh and pelvis and, using
compressed air, sequential pressure (up to 300 mmHg) is applied in early diastole
to propel blood back to the heart
Increase exercise capacity
Decrease angina episodes & use of nitroglycerin
In one study MACE-free survival was 70 percent

Neuromodulatoin (SC stimulation or Sympathectomy)
Spinal cord stimulation
stimulation at T1-T2 is another approach to management of refractory angina
Spinal cord stimulation was originally developed to treat neurogenic pain
Its mechanism of action is poorly understood
May have effects on angina by suppressing capacity of cardiac neurons to
generate activity during myocardial ischemia
May ↓sympathetic tone or redistribute BF from nonischemic to ischemic areas

Coronary sinus reducing device
Balloon catheter is inserted into the coronary sinus percutaneously & the balloon
expanded to implant an hourglass-shaped metal mesh that leads, over time, to
partial obstruction of the coronary sinus
postulated that development of an upstream pressure gradient favors perfusion of ischemic
territories
Transmyocardial laser revascularization

References
Brauwald’s Heart Disease, 11th
Edition
Harrison’s Principle of Internal Medicine, 20th
Edition
2019 ESC guideline for the diagnosis and management of CCS
Uptodate, 2018
Internate sources

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