Ch 54 Stable CAD

Generalities
• Most commonly caused by atheromatous plaque that obstructs or gradually
narrows one or more of the epicardial vessels
• Causes
• Obstructive atherosclerotic
• Obstructive non atherosclerotic
• congenital abnormalities
• myocardial bridging,
• coronary arteritis
• radiation-induced CAD

• Non obstructive
• HOCM
• Aortic stenosis
• ICMP
Generalities
• Presentation of IHD
• Angina
• Angina Equivalent/Atypical
• gastric discomfort, effort intolerance, dyspnea, and excessive fatigue
• common in women, DM, elderly
• Arrhythmia
Magnitude of the Problem
• lifetime risk for symptom development after 40 years old
• 49% for men
• 32% for women
Clinical Manifestations
• Postprandial angina
• presumably caused by redistribution of coronary blood flow, may be a marker
of severe CAD
Clinical Manifestations
• Begins gradually, reaches maximum intensity over a period of minutes
before dissipating
• Relieved by rest, sitting, stopping when walking, intake of short acting nitrates
within MINUTES.
• IF it lasts MORE THAN 5-10minutes, it is either SEVERE ANGINA or not
ischemia at all
• ***Chest discomfort while walking in the cold or uphill is suggestive of
angina
Clinical Manifestations
• Warm up angina or First Effort Angina
• requires preceding ischemia of at least moderate intensity to induce this
phenomenon
• Patient exercises-> angina develops -> patient rests -> angina relief -> exercise
again at same intensity or higher -> no more angina
• Mechanism: Ischemic preconditioning
Grading of Angina Pectoris
• CCS score
• Goldman angina score
• uses specific METS of activities
• Calif angina score
• uses ST-T wave changes
• includes age, sex, left ventricular (LV) function, and coronary angiographic
anatomy
• has prognostic significance
 Mechanism of Angina

Ischemia  Release of chemicals Stimulation of Receptors Nerve Conduction

1. Bradykinin vanilloid receptor-1 (VR1)

• Referred Pain in the chest arms and epigastrium

• Cause: Convergence of cardiac sympathetic afferent fibers from the thorax to the chest
• Referred pain in the neck and jaw
• Cause: Cardiac vagal afferent synapse in the nucleus tractus solitarius to the upper cervical spinothalamic cell
• Nausea and vomiting in MI
• Cause: vagal input in the nucleus tractus solitarius stimulates efferent impusles
 Mechanism of Angina

Silent Ischemia
1. Abnormal Sensory afferent nerves
- seen in DM patients
2. Autonomic Neuropathy
3. Impaired transmission from thalamus to neocortex
 Differential Diagnosis

1. Esophageal Disorders (Diffuse spasm, nutcracker esophagus)

• relieved by NGT also
• esophageal pain is often relieved by milk, antacids, foods, or occasionally, warm liquids
2. Esophageal Motility Disorders
• dysphagia
• poor symptomatic response to antianginal therapy in the absence of documented ischemia
3. Biliary Colic
• atypical chest pain that is usually steady and lasts for 2-4 hrs and subsides spontaneously
• may radiate to scapula, costal margin to back, or rarely in diaphragm
4. Costochondritis
• tenderness of the costochondral junctions (without swelling)
• does not exclude symptomatic CAD
5. Musculoskeletal pain
 Differential Diagnosis

• Other Causes of Angina like pain

• Severe pulmonary hypertension
• Pulmonary Embolism
• Pleuritic pain suggests pulmonary infarction
• Acute pericarditis
• Aortic dissection
 PE

• May have normal PE

• single best clue to the diagnosis of angina is the clinical history
 Pathophysiology

• Angina Caused by Increased Myocardial O2 Requirements

• Angina Caused by Transiently Decreased O2 Supply
Angina Caused by Increased Myocardial O2 Requirements

• Exertion/Stress/physical exertion -> increase myocardial O2

demand release of NE/catechloamines -> increased adrenergic
tone -> angina
• also known as demand angina

**Stress: physical exertion after heavy meals, thyrotoxicosis, fever,

exposure to cold, hypoglycemia etc
Angina Caused by Transiently Decreased O2 Supply

• condition known as supply angina

• dynamic stenosis ->platelet thrombi and leukocyte elaborate
vasoconstrictor substances (serotonin and thromboxane A2)->
coronary vasoconstriction -> endothelial damage
• Variable threshold angina
• dynamic changes in peristenotic smooth muscle tone and also by constriction of arteries distal to
the stenosis
• circadian variation more common in the morning
Importance of Pathophysiologic Considerations for therapy

• Demand angina/ Increased O2 demand

• Use beta blockers
• Supply angina/ Decreased O2 supply
• Use nitrates, CCB
Evaluatio
n
Biochemical Test

• All patients with supspected or established CAD

• lipid profile
• serum creatinine (eGFR)
• fasting blood glucose
• Other tests
• lipoproteins, apo B, small LDL
• non HDL calculations (check for residual vldl)
• Lp-PLA
• risk for coronary heart disease (CHD) and recurrent event
• Homocysteine
• modest increase in CAD risk
• not routinely recommended
• hsCRP
• maybe beneficial for intermediate risk for additional prongnosticator
• >2mg/L if treated with statin- reduction of CV death
• statin lowers hscrp
Biochemical Test

• BNP
• prognosticator
• may not have sufficient specificity to aid in the diagnosis of SIHD
• MR-proADM
• MR-proANP
• Growth differentiation factor-15
• ST2
• galectin-3
Biochemical
Tests
Electrocardiogra
m
• RESTING
• Normal in ~50% of cases (even in those
with SEVERE CAD)
• A normal resting ECG is suggestive of a
normal resting LV function
• Unusual in patients s/p MI
• Most common finding: NSSTTWC with or
without Q waves
• CLBBB, LAFB, LVH – suggests poor
prognosis in CSA
• ANGINA
• Abnormal in 50% of cases
• Most common finding: ST-segment
depressions or inversion
(pseudonormalization)
Electrocardiogra
m
• Ischemia
• Reduce the resting membrane potential
• Shortens duration of action potential
• Decreases the rate of rise and amplitude of phase 0 in the ischemic area
• Creation of a voltage gradient between normal and ischemic zones

• During electrical diastole

• Ischemic cells remain relatively depolarized (related to potassium ion
leakage, during phase 4 of the ventricular action potential)
• When ischemia is confined primarily to the subendocardium, ST vector shifts
towards the inner ventricular layer € ST - DEPRESSION
Electrocardiogra
m • Deep coronary T-wave inversion in
multiple precordial leads V1-4) may
occur without cardiac enzyme
elevation
• Results of severe ischemia with a high
grade stenosis

• Patients with Twave inversion/

depression on baseline ECG can
experience paradoxical T wave
normalization during episodes of acute
transmural ischemia
Non invasive Stress Testing

• should be performed only if a test is likely to alter the planned

management strategy
• The value of noninvasive stress testing is greatest when the
pretest likelihood is intermediate because it is likely to have the
greatest effect on the post-test probability of CAD
Exercise
Electrocardiography
• Exercise Electrocardiography
• helpful in patients with moderate
probability of CAD and normal resting
ECG, provided that they are capable of
achieving an adequate workload
• In low or high CAD probability, it can
provide degree of functional limitation,
severity of ischemia and prognosis
Exercise
Electrocardiography
• Exercise Electrocardiography
• Long acting beta blockers
• Stop 2-3days before test
• Short acting beta blockers, ca channel blockers and long acting nitrates
• Stop a day before
Exercise
ECG
Exercise • Chronotropic incompetence
• Inability of the heart to increase its
ECG rate to meet demand
• Independent risk factor for all
cause mortality
• Failure to achieve chronotropic
index higher than 80% (62% if on beta
blockers but unacceptable)
• Submaximal study
• Peak heart rate achieved is
below age-predicted max HR

• Inadequate / non-diagnostic
Chronotropic
Index study
• Failure to achieve a predefined goal
Exercise
ECG
• Not reliable in women

• Early Heart Rate Acceleration

• Deconditioning
• AF, hypovolemia, anemia, LV Dysfunction
• Should not be considered in the evaluation of exercise test results

• Heart Rate Recovery

• abnormal results is associated with increased all cause mortality
• 12 bpm after 1minute with cool down
• 18bpm after 1minute with immediate cessation of movement into supine or
sitting
• 42bpm after 2minutes
Exercise
ECG
• Double product = HR and blood
pressure product, normally higher
than 20,000
• SBP increases steadily, DBP increases only
minimally or remains the same
• Exaggerated Systolic Pressure
response:
• >210mmHG in men
• >190mmHG in women
• Exercise induced hypotension
• SBP 20mmHg after an initial rise
> predictive of poor prognosis related
to multivessel CAD
• Fall in SBP below resting SBP
• Low Systolic Pressure Peak
• Rise to less than 140mmHG or a
lower
than 10mmHG rise overall
• Recovery Systolic Pressure
Response
• No established definition
• Ratio of 1-, 2- and 3-minute
recovery pressure.
• If >0.9 = worse CV prognosis
• Double product reserve
• Difference between the peak
and resting double product
• Inversely related to CV events in
patients with and without
known CAD
White PTP <15%
Blue PTP 15-65%
Light red PTP 66-
85%
Stress Myocardial Perfusion
Imaging
• Exercise MPI
• superior to an exercise ECG alone in detecting CAD
• identifies multivessel CAD and magnitude of ischemic and infarcted
myocardium and for viability testing
• should not be used as a screening test in with low CAD prevalence (high false
positive); regular ECG stress test first
• Pharmacologic vasodilatation
• dipyridamole or adenosine
• Vasodilator stress is comparable to exercise MPI, but exercise MPI has
more useful prognostic data (ST-segment changes, effort tolerance and
symptomatic response, and heart rate and blood pressure response )
Echocardiograp
hy
•
Not necessary for all patients with angina pectoris and in
patients with normal ECG and no previous history of MI
Stress
Echocardiography
• Sensitivity for significant CAD (>50% stenosis by angiography) averages
approximately 88% (range 76 – 94%)
• Specificity 83%
• Accuracy similar to stress MPI
• Protocol
• Bruce protocol
• Imaging at rest and immediate recovery period as close to peak exercise as possible
• IF unable to exercise, pharmacologic with graded dobutamine infusion of up to
40ug/kg/min
+ atropine to increase heart rate
• Test is completed if completed by exercise limiting symptoms or completion of protocol
• Absolute indications to terminate the test early
• moderate to severe angina, ST-segment elevation, sustained ventricular tachycardia, near syncope or
signs of poor perfusion, a drop in systolic blood pressure of more than 10 mm Hg from baseline
when accompanied by any other evidence of ischemia, and patient request to stop (intolerable
symptoms).
Stress
Echocardiography
• With stress the ventricle should become hypercontractile and
the cavity size should shrink.
• The presence of baseline wall motion abnormalities that remain
“fixed” (unchanged) with stress is indicative of a previous
infarct.
• The development of a new or worsening wall motion abnormality
indicates a flow-limiting stenosis in the coronary artery supplying
the abnormal segment or segments
• A large ischemic territory (i.e., left main or multivessel disease) will
be manifested as diminished global LVEF and chamber dilation with
stress.
Stress
Echocardiography
•
Limitations
• False negative occurs when/during
• Suboptimal level of stress (inadequate exercise, beta blockers)
• There is limited image quality
• There is small area of ischemia
• Left ventricular hypertrophy
• Hyperdynamic state
• False positive occurs when/during
• Low pretest probability
• Presence of LBBB or septal dysynchrony (pacing or postoperative
state)
• Exercise exaggerates abnormal septal motion. DSE is recommended
• Assessment of wall thickening rather than excursion is more helpful
Stress
Echocardiography
•
Limitations
• Other conditions that can cause nonspecific or non-diagnostic findings
include
• presence of preexisting wall motion abnormalities that tether adjacent segments,
• severe hypertension
• HCM
• cardiomyopathies in which myocardial perfusion reserve is diminished as a result
of microvascular disease
Stress
Echocardiography
•
Risk Stratification with Stress Echocardiography
• Normal exercise or pharmacologic stress echocardiograms
• very low risk of cardiac event
• Close to that of a “normal” population
• Exercise: <1% per year
• Pharmacologic: <2% per year
• Suspected or known CAD
• extent of resting wall motion abnormalities and ischemia
• fourfold or greater increased risk for cardiac death or I
Stress
Echocardiography
• Assessment of Viability
• MOST Specific sign: Biphasic response
• improvement in wall thickening at low-dose dobutamine but then
deteriorates with high-dose dobutamine
• Viable: Any improvement in wall motion abnormality by at least one grade in
two or more segments during stress
Clinical Application of Non invasive Testing
• Sex difference
• ECG stress in not reliable in women (less specific for women)
• Exercise imaging modalities have greater diagnostic accuracy than does
exercise electrocardiography in men and women
• Stress exercise test is still the modality of choice for both men and women

• Perform CA if with high risk non invasive results

Clinical Application of Non invasive Testing
• Indications for exercise stress test for asymptomatic patients
• diabetes mellitus who plan to begin vigorous exercise
• high-risk professions (such as airline pilots)
• evidence of myocardial ischemia on other noninvasive testing (e.g. severe
coronary calcifications on cardiac CT)
Chest X-
Ray
•
If cardiomegaly is present it is indicative
of
• Severe CAD with previous MI
• Pre-existing HPN
• Associated nonischemic condition (Valve)
• Cardiomyopathy
Computed
Tomography
• Uses
• highly sensitive for detecting coronary calcification
• provide angiography of the coronary arterial tree
• assessment of myocardial perfusion
• quantification of ventricular function and myocardial
viability
• plaque characterization
Computed
Tomography
• High sensitivity – 90%
• Low specificity - ~50%
• Not recommended as a routine approach to screening for CAD
in individuals at low risk of IHD (<10% 10-year estimated risk
for coronary events)
• Reasonable screening for intermediate risk
• clinical strength is the ability to r/o significant CAD with a high
negative predictive value
Cardiac MRI
• Clinical Uses
• Myocardial viability
• accurate LV function
• Ischemic from nonischemic myocardial dysfunction
• characterize arterial atheroma and assess vulnerability to
rupture congenital anomalies
• stenoses in the proximal and middle segments of major
epicardial vessels or surgical bypass grafts
Stress testing and advanced imaging for patients with known SIHD
who require non-invasive testing for risk assessment
Stress testing and advanced imaging for patients with known SIHD
who require non-invasive testing for risk assessment (cont.)
Goal of non-invasive
testing
Catheterization, Angiography and Coronary
Arteriography
• To make a definitive diagnosis
• Patients with CSA
• 25% Single Vessel
• 25% Two-vessel
• 25% Triple Vessel
• 15-25% No critical obstruction detected

• 5-10% of those with obstruction, have left main coronary artery involvement

• Patients with UNHERALDED MI have FEWER diseased vessels, stenosis

and chronic occlusions and less diffuse disease than patients with CSA

• In patients with SIHD with previous history of MI, there is a total occlusion of at
least 1 major coronary artery
Catheterization, Angiography and Coronary
Arteriography
• Coronary Flow Reserve = Max flow/Resting Flow
• Coronary Artery Ectasia and Aneurysms
• 50% are caused by coronary atherosclerosis and the
rest are congenital
• Ectasia does not affect prognosis
• almost never found in arteries without severe
stenosis
• most common in the LAD and usually associated
with extensive CAD
• Aneurysms
• don't appear to rupture
• do not warrant resection
 Catheterization, Angiography and Coronary
Arteriography
• Coronary Collateral Vessels
• collateral vessels protect against resting ischemia but not against exercise-induced
angina
• MI size is smaller in pxs with abundant collaterals
• Myocardial Bridging
• <5%
• increased myocardial bridge thickness and length, proximal vessel location,
correlated with increased risk for MI due to promotion of proximal atherosclerosis
• LV function
• Myocardial Metabolism (coronary venous lactate)
 Natural History and Risk Stratification
• Women=Men incidence of stable angina
• Annual mortality rate of 1% to 3%
• Rate of major ischemic events of 1% to 2%
• Clinical criteria
• age
• male sex
• diabetes mellitus
• previous MI
• symptoms typical of angina
• predictive of the presence of CAD
 Natural History and Risk Stratification
• Exercise ECG
• peak exercise capacity in metabolic equivalents is the strongest predictors of
mortality in men with cardiovascular disease
• Stress MPI
• low (<1% with a normal MPI study)
• intermediate (1% to 5%)
• high (>5%) risk
• Echocardiography
• LV function is one of the most valuable aspects
• Negative stress echo portends a low risk for future events (<1% annual
mortality)
 Natural History and Risk Stratification
• Extent of CAD
• High-grade lesions of the left main coronary artery or its equivalent
• severe proximal LAD and severe proximal LCX
• Limitations of Coronary Angiography
• >60% stenosis reduces coronary blood flow on exercise
• Not a reliable indicator of the functional significance of stenosis
• inability to identify high risk or vulnerable coronary lesions- most serious limitation
• two thirds to three quarters or ruptured plaques have <50% of the luminal
diameter
Medical
Management
Five aspects
• identification and treatment of associated diseases
• reduction of coronary risk factors
• pharmacologic and non pharmacologic interventions for
secondary prevention
• pharmacologic management of angina
• revascularization by PCI/CABG
Medical Management
• Reduce morbidity and mortality in SIHD and preserved LV
function
• aspirin
• angiotensin-converting enzyme [ACE] inhibition
• effective lipid lowering
• BB (if with LV dysfunction)
 Treat Associated
Diseases Reduce CAD
•Risk Factors
Cocaine – acute coronary spasm, MI
• anemia, marked weight gain, occult thyrotoxicosis, fever, infections,
and tachycardia
• Heart failure – increased myocardial demand via cardiac dilation,
MR, tachyarrhythmia
 Treat Associated
Diseases Reduce CAD
•Risk Factors
Hypertension (for individuals 40-70 years old)
• Risk for IHD doubles for each 20mmHg increase between 115-185mmHg
• LV hypertrophy – stronger predictor of MI and CAD death than elevated BP
• BP goal <140/90mmHg , more beneficial in older
• Treatment of mild to mod HPN16% reduction in events and mortality
• ACCORD-BP
• No additional benefit in further lowering systolic blood pressure below 120
mm Hg in DM patients
• Smoking
• incrases myocardial O2 demand by alpha-adrenergically mediated increased
coronary artery tone
• cost effective approach in preventing disease progression in native and
bypass graft
 Treat Associated
Diseases Reduce CAD
•Risk Factors
Dyslipidemia tx
• regression of atherosclerosis is not the primary mechanism of benefit of
statins
• improve endothelium-mediated responses
• reduce circulating levels of hsCRP
• decrease thrombogenicity and alter the collagen and inflammatory
components of arterial atheroma
• high intensity statins in established IHD who are less than 75 years of age,
 Treat Associated
Diseases Reduce CAD
•Risk Factors
Dyslipidemia
• Low HDL
• considered risk for future coronary events
• VA-HIT
• Gemfibrozil increases HDL by 6% and decreases TG in 31%
• ILLUMINATE trial
• cholesteryl ester transfer protein (CETP) inhibitor, increased HDL
cholesterol by 61% and reduced LDL cholesterol by 20% but did not
decrease progression of atherosclerosis
• negative effect of Torcetrapib due to increase in BP
 Treat Associated
Diseases Reduce CAD
•Risk
ManageFactors
DM
• Estrogen replacement
• not advisable
Treat Associated
Diseases Reduce CAD
•Risk Factors
Exercise
• Avoid weightlifting and energy expenditure between 60-65% of peak O2
consumption
• Avoid sudden bursts of activity
• Sexual intercourse = 1 flight of stairs at normal pace or any activity
that induces HR of 120bpm
• May be reduced by taking beta blockers 1hour and NTG 15mins prior to sex
• Obesity – independent contributor to the risk for IHD,
associated with
• Hypertension, dyslipidemia, abnormal glucose metabolism
• Inflammation – atherothrombosis
Secondary Prevention

• Aspirin 75 to 162 mg daily

• Other antiplatelets if hypersensitivity to ASA
• Clopidogrel
• CAPRIE: clopidogrel equivalent to ASA in stable CAD
• CHARISMA: no benefit for DAPT in SIHD
• Voraxpar
• reduced the risk for recurrent major CV events in patients with
previous MI monitored for 2.5 years but increased risk of bleeding

• Beta Blocking agents

• value in CSA is less certain
• mortality benefit in ACS
Secondary
Prevention
•
ACE inhibitors and ARBs
• reductions in LV hypertrophy, vascular hypertrophy, progression
of atherosclerosis, plaque rupture, and thrombosis, inflamation
• HOPE
• P – CSA, Normal LV, No HF
• O – reduced relative risk of cv events by 22%
• I – Ramipril
• M - RCT
• EUROPA
• P – CSA, Normal LV, No HF
• O – relative risk reduction of cv events by 20%
• I – Perindopril
• M – RCT
Secondary
Prevention
•
ACE inhibitors and ARBs
• PEACE
• trandolapril showed no effect on the risk for cardiovascular death, MI, or coronary
revascularization
• CONCLUSION
• ACE inhibitors are recommended for all patients with CAD and LV dysfunction,
hypertension, diabetes, or chronic kidney disease.
• ACE inhibitors may be considered for optional use in all other patients with SIHD, a
normal LV ejection fraction, and well-controlled cardiovascular risk factors in whom
revascularization has been performed.
• Combination of telmisartan and ramipril provided no additional benefit over ramipril
alone
Secondary
Prevention
•
Antioxidants
• no basis for recommending that individuals with IHD take supplemental folate, vitamin E,
vitamin C, or beta-carotene for the purpose of improving cardiovascular outcome
Counseling and Changes in Lifestyle

• SSRI for depression

• Avoid isometric exercises
• Sexual intercourse is approximately equal to that of climbing one
flight of stairs at a normal pace or any activity that induces a heart
rate of approximately 120 beats/min
• prophylactic use of short-acting nitrates several minutes before for prevention of angina
• may start 2 hrs post prandial and additional short acting beta blockers 1 hr before NTG and 15 min
before NTG
• Sildenafil but not in conjunction with nitrates
Pharmacologic Management of Angina
 Beta
•Blockers
Cornerstone of therapy for angina
• Uses
• Antihypertensive and anti arrhythmics
• Reduce mortality and reinfarction in MI and HF
• reduces myocardial O2 requirement by slowing HR
• reduce exercise-induced increases in BP
• limit exercise-induced increases in contractility
 Beta
Blockers

Effects of beta blockade on an ischemic heart has a beneficial effect on

ischemic myocardium unless (1) the preload rises substantially, as in
left-sided heart failure, or (2) vasospastic angina
Selectivity

• Beta 1
• predominates in heart
• increase in heart rate, atrioventricular (AV) conduction, and
contractility
• release of renin from juxtaglomerular cells in the kidneys and
lipolysis
• Beta 2
• bronchodilation, glycogenolysis, vasodilation
• As the doses of the drugs are increased, this cardioselectivity
diminishes.
Beta
Blockers
Non-Selective Cardioselective Vasodilating effect
(alpha-adrenergic
and B2 )
Propranolol Acebutolol Labetalol
Nadolol Atenolol Carvedilol
Penbutolol Betaxolol Nebivolol
Pindolol Bisoprolol Bucindolol
Sotalol Esmolol
Timolol Metoprolol (LBCN)
Carteolol Nebivolol
(PNP STC) (AABBMEN)
 Beta
•Blockers
Intrinsic sympathomimetic activity
• Partial beta agonist that produce blockade by shielding beta receptors from
more
potent beta agonists
• Pindolol and acebutolol – low grade beta stimulation when sympathetic activity
is low
• Others: bucindolol, carteolol, celiprolol, penbutolol
• Most potent – timolol and pindolol
• Least potent – acebutolol and labetalol
• Lipid soluble – propranolol, metoprolol, pindolol
• readily absorbed from the GIT and metabolized by the liver (preferable if with significant
renal disease)
• greater CNS penetration (side effects like depression and hallucination)
• Water soluble – atenolol (eliminated unchanged in kidneys)
• Alpha blockade – labetalol, carvedilol
 Beta
•Blockers
Genetic Polymorphism

• Effects in lipid profile

• Usually increase TG and decreased HDL
• More B1 selective has less lipid side effects
Beta Blockers: Adverse Effects and Contraindications

• Carvedilol
• has insulin sensitizing abilities
• Pindolol
• more effective in sinus node dysfunction due to ISA
• Non-selective beta blockers can trigger Reynauds (due to vasoconstriction of
b2 blocker)
• Abrupt withdrawal of beta blockers can increase total ischemic activity
• Chronic beta blocker therapy can be safely discontinued by slowly
withdrawing the drug in a stepwise manner over the course of 2 to 3 weeks
• If abrupt withdrawal is needed, ca antagonist or nitrates can be given for
angina
Calcium
Antagonists
Mechanism of action
• noncompetitive blockade of voltage-sensitive L-type calcium
channels
• negative inotropic effect- caution if with LV dysfunction
• peripheral vasodilation
• activation of sympathetic nervous system in response to drug
induced hypotension

Antiatherogenic Action
• Amlodipine- improves endothelial function
Calcium
Antagonists
• Dihydropyridines – nifedipine, amlodipine, felodipine,
nicardipine
• Phenylalkylamines – Verapamil
• Modified benzodiazepine – Diltiazem
First Generation Calcium Antagonists
• Nifedipine
• more potent vasodilator
• Avoid short acting nifedipine (hypotensive effect within 20 min)
• Long-acting nifedipine should be considered an effective and safe antianginal who are
already receiving beta blockers with or without nitrates
• Adverse effects (peripheral vasodilation)
• head- ache, dizziness, palpitations, flushing, hypotension, and leg edema (unrelated to
heart failure)
• Contraindicatons
• hypotensive and severe aortic stenosis
First Generation Calcium Antagonists
• Verapamil
• dilates systemic and coronary resistance vessels and large coronary conductance vessels
• INVEST (International Verapamil- Trandolapril Study
• verapamil and trandolapril versus atenolol and a diuretic for hypertension and CAD,
with previous MI, showed equivalent outcomes with death, MI, or stroke
• slows the heart rate and AV conduction
• bioavailability of verapamil is increased by cimetidine and carbamazepine
• verapamil may increase plasma levels of cyclosporine and digoxin
• Adverse effects:
• hypotension and facial flushing
• gastrointestinal symptoms (constipation and nausea)
• headache and dizziness
• gingival hyperplasia (after 1-9 mo of tx)
First Generation Calcium Antagonists
• Diltiazem
• intermediate between nifedipine and verapamil
• vasodilator: diltiazem<nifedipine
• cardiac depressant: diltiazem<verapamil
• may enhance perfusion of subendocardium distal to a flow-limiting coronary stenosis
• blocks exercise-induced coronary vasoconstriction
• Major side effects are infrequent
• Increases bioavailability of diltiazem (cimetidine and flecainide)
• Diltiazem increases plasma levels of cyclosporine, carbamazepine, lithium
• excessive sinus node depression if with disopyramide
• reduce digoxin clearance if with renal failure
Second Generation Calcium
Antagonists
• Amlodipine
• marked coronary and peripheral dilation and is useful for angina with hypertension
• plasma half-life 36 hrs
• has very little negative inotropic effect so can be used in pxs with LV dysfunction and
chronic angina
• Dose: 5mg to 10mg od (adjustment of elderly and with liver disease)
• Significant changes in blood pressure: 24 to 48 hours after initiation
• Steady- state serum levels: 7 to 8 days
Second Generation Calcium
Antagonists
• Nicardipine
• half-life similar to that of nifedipine (2 to 4 hours)
• greater vascular selectivity
• antianginal and antihypertensive
• efficacy is enhanced when combined with a beta-blocking agent
Second Generation Calcium
Antagonists
• Felodipine and Isradipine
• tx for hpn but not for angina
• felodpine
• more vascular selective
• mild positive inotropic effect
Nitrate
s• Mechanism of Action
• relax vascular smooth muscles predominantly in the venous
leading to reduce ventricular preload
• improve exercise tolerance and time to ST-segment depression during
exercise tests
Nitrate
s• Effects on Coronary Circulation
• NTG causes dilation of epicardial stenoses
• alleviates the vasoconstriction caused by endothelial dysfunction of resistance vessels
• Redistribution of Blood Flow
• NTG causes redistribution of blood flow from normal perfused segment to areas
with ischemia (subendocardium)
• reduced coronary vascular resistance
• Antithrombotic Effects
• Stimulation of guanylate cyclase by nitric oxide (NO) results in inhibitory action on
platelets in addition to vasodilation
 Nitrate
s• Cellular Mechanism of Action
• Nitrates have the ability to cause
vasodilation, regardless of
whether the endothelium is
intact.
• Nitrates -> NO in smooth muscle
cells -> production of cGMP->
smooth muscle relaxation and
antiplatelet aggregator effects
• Nitrate tolerance
• due to inhibition of
mitochondrial aldehyde
dehydrogenase responsible
for biotransformation of NTG
Types of Preparations and Routes of Administration

• Short-acting nitroglycerin
sublingually
• drug of choice for the
treatment of acute angina
episodes and for
prevention of angina
• useful when taken
prophylactically shortly
before physical activities
• may prevent angina for
up to 40 minutes
Adverse Reactions of nitrates

• headache, flushing, and hypotension

• nitrate-induced hypotension is accompanied by a paradoxical
bradycardia in volume depleted
• methemoglobinemia

• Severe hypotension when given with patients on PDE 5 inhibitors

(sildenafil, tadalafil, vardenafil)
• Avoided by stopping within 24hours of any nitrate preparation
Nitrate
s
Potential for Adverse Effects During Long-Term Administration.
• Extended exposoure to nitrates can impair endothelial
dependent vasocdilation through increases in endothelin-1 and
generation of free radicals
Preparation of nitrates
• SHORT-ACTING NITROGLYCERIN (NITROGLYCERIN TABLETS AND ORAL SPRAY)
• aerosolized doses of 0.4 mg may be better absorbed than the sublingual
• longer shelf-life
• ISOSORBIDE DINITRATE
• Partial or complete nitrate tolerance(if 30mg 3 or 4x daily)
• Allow 10-12 hr nitrate free interval to avoid
• ISOSORBIDE 5-MONONITRATE
• peak between 30 minutes and 2 hours after ingestion
• half life: 4-6 hrs
• tolerance is more common in twice dailly dosing as compared to once daily
• TOPICAL NITROGLYCERIN (transdermal patch)
• absorption for 24 to 48 hours
• increase exercise duration and maintain its anti-ischemic effects for 12 hours
• Remove patch after 12 of 24 hours
Nitrate Tolerance
• limited to capacitance and resistance vessels
• Mechanism
• increased vascular superoxide anion (⋅O2−) is central to the process may lead to
• plasma volume expansion and neurohormonal activation
• impaired biotransformation of nitrates to NO
• decreased end-organ responsiveness to NO
• Management
• 12 hour off period
• pentaerythrityl tetranitrate is an organic nitrate that may have lesser detrimental
effects on mitochondrial aldehyde dehydrogenase
Nitrate Withdrawal
• angina is intensified after discontinuation of large doses of long-acting nitrates
• Tx
• adjusting the dose and timing of administration in addition to the use of other
antianginal drugs
Other anti-
anginals
• Ranolazine
• anti-ischemic effects with no changes in HR or BP
• reduction in calcium overload in ischemic myocytes via inhibition of the late inward sodium
current (INa)
• reduction in angina and improvement in exercise performance were evident only in chronic
angina
• Uses/Properties of ranolazine
• reduce periprocedural myocardial injury (PCI)
• improved exercise performance and increased the time to ischemia
• decreases angina frequency and NTG use when used in conjunction with BB and CCB
• reduced symptoms with evidence of an improved myocardial perfusion reserve index
• anti-arrhythmic effects
• inhibition of the delayed rectifier current and inhibition of Ina hence shortens AP
and suppress early after depolarization
• reduction in Hba1c- on going study
Other anti-
anginals
• Ranolazine
• Studies
• CARISA (Stable CAD), ERICA (Stable CAD), MERLIN (NSTE ACS)
• ranolazine, administered for an average of approximately 1 year, did not add to
standard therapy in secondary prevention of major cardiovascular events
Other anti-
anginals
• Ranolazine
• Pharmacology
• Half life: 7 hrs
• steady state is within 3 days of twice-daily dosing
• Dose: 500 mg twice daily, max of 1000mg twice daily
• Contraindications
• prolonged QTc interval
• simvastatin of >20mg daily
• Plasma concentrations of simvastatin are increased approximately twofold
Other anti-
anginals
• Ranolazine
• Adverse effects
• nausea, generalized weakness, and constipation
• dizziness
• increase in corrected QT (QTc) interval, an average of 2 to 5 milliseconds
Other anti-
anginals
• Ivabradine
• Inhibits If channelreducing spontaneous firing rate of SA pacemaker
• For chronic heart failure in combination with standard therapy in heart rate >75
• reduce HR without ventilatory effect
• CAD with LVD
• did not reduce the primary endpoint of cardiovascular death, hospitalization for MI, or
hospitalization for heart failure
• Limiting angina with HR >70
• reduce CV death or hospitalization for worsening heart failure, reduced ejection
fraction, and heart rate of 70 beats/min or higher
Other anti-
anginals
• Nicorandril
• Nicotinamide ester that dilates peripheral and coronary resistance vessels via action on ATP
sensitive potassium channel
• possesses a nitrate moiety that promotes systemic venous and coronary vasodilation
• Reduces preload and afterload
• cardiprotective effect: Potassium activator
• Antianginal efficacy similar to BB
• Reduced the risk for cardiac death, MI or hospital admission for angina
• Associated with ulceration of GIT
Other anti-
anginals
• Metabolic agents
• Trimetazidine and perhexiline
• inhibit fatty acid metabolism and reduce the frequency of angina without
hemodynamic effects in CSA
• Partial inhibitors of fatty acid oxidation appear to shift myocardial metabolism to
more oxygen-efficient pathways
Choice of Initial
Therapy
•Prinzmetal angina
• Calcium channel blockers or long
acting nitrates
• Heart failure – Beta blockers; i.e.
GDMT
• Symptomatic conduction disease
• Pindolol (greatest ISA)
• Suspected PAD
• CCB
• CAD with LVD intolerant of BB
• Amlodipine
Combination therapy
• calcium antagonists + beta blockers should be avoided or with caution
• amlodipine is the choice
• dihydropyridine CCB + long-acting nitrate (without a beta blocker)
is not an optimal combination because both are vasodilators
Approach to CSA Management

• Identify and treat precipitating factors

• Risk factor modification (high intensity statins; LDL<100 goal)
• ACEI in all EF<=40, hypertension, diabetes, or chronic kidney
disease
• SL nitrates for symptoms
• CCB/long acting nitrates for angina with proper dosing schedule in
order to prevent nitrate tolerance
• If angina persists despite 2 agents, add third drug
• Coro angio if with refractory symptoms despite OMT
Non Pharmacologic Approach

Enhanced External Counterpulsation

- active counterpulsation was associated with an increase in time to
ST-segment depression during exercise testing and a reduction in
angina
- No definitive data that EECP reduces the extent of ischemia as
determined by MPI

Spinal Cord stimulation

Outcome
s•
Without OMT – 4% annual mortality
• With OMT – 1-3% annual mortality, 1-2% major ischemic
events
 Pharmacological treatments in SCAD
Indication
patients AHA (2012) ESC (2013) PHA (2014)
General Considerations
OMT (1 drug for angina/ischemia relief plus event prevention) - IC -
Patient education I B,C IC -
Review patient’s response - IC -
Angina/ischemia relief
Short acting nitrates IB IB -
1st line Beta blockers or CCB to control HR and symptoms IB IA IA
Beta blockers for patIents with HFrEF (EF <40) IA - -
Beta blockers for patients post ACS (up to 3 years) IB - -
2nd line – long acting nitrates, ivabradine, nicorandil, ranolazine Iia B Iia B Iia B
2nd line – trimetazidine - Iib B Iib B
Use 2nd line as 1st line depending on comorbidities/tolerance - IC -
Consider BB in asymptomatic patients with large areas of ischemia (>10%) - Iia C -
In patients with vasospastic angina, CCB and nitrates should be considered and - Iia B -
BB avoided
 Pharmacological treatments in SCAD
patients
Indication AHA (2012) ESC (2013) PHA (2014)
Event Prevention
Low dose ASA IA IA IA
Clopidogrel is indicated as an alternative to ASA if not tolerated IB IB IB
DAPT IB - -
Statins IA IA IA
IF statin is not tolerated, may give bile sequestrants, niacin, etc. Iia B - -
ACE/ARBs (if ACE intolerant) if there are other conditions (HF, HPN, DM) IA IA -
ACEi /ARBs (if ACE intolerant) for other vascular disease IB - IA
Lifestyle modification, physical activity, weight management IB - R
Diet IB - R
Combined statins, lifestyle modification, diet IA - -
Influenza vaccine IB - -
Revascularization
Patient Selection for Revascularization

• presence and severity of symptoms

• physiologic significance of the coronary lesions
• extent of myocardial ischemia and the presence of LV dysfunction
• other medical conditions that influence the risks associated with
percutaneous or surgical revascularization
Presence and severity of symptoms

• Mechanical revascularization (catheter based or surgical) should be

considered if ischemic symptoms persist after intensification of
medical therapy
Significance of Coronary Lesions (and
other Anatomic Considerations)
• Seventy percent or greater stenosis of an epicardial coronary artery
is considered to be anatomically significant (≥50 for left main
coronary stenosis)
• No anatomic subset of CAD stenosis severity (INCLUDING: 70-90%
narrowing and >90% narrowing of LAD) was found to benefit from
PCI versus OMT with respect to long term clinical outcomes
• Basis: Courage Trial
Significance of Coronary Lesions (and
other Anatomic Considerations)
• Other factors can potentially render a 50% to 70% stenosis
“functionally or hemodynamically significant
• lesion eccentricity
• tortuosity
• presence of plaque rupture
• asymmetric luminal filling defects
• presence of additional serial lesions
Significance of Coronary Lesions (and
other Anatomic Considerations)
• FFR
• pressure or flow distal to a stenosis relative to the pressure or
flow before the stenosis (distal/prox)
FFR

• FAME
• P –SIHD
• I – FFR guided PCI versus angiographically directed PCI
• O – lower 2 year rate of death or MI with FFR guided strategy
• M – RCT

• FAME2
• P –SIHD with FFR of 0.8 in one or more stenotic coronary arteries
• I – OMT versus PCI + OMT
• O – 68% relative risk reduction in primary endpoint from 12.7% in medical to 4.3%
in
the PCI group. No significant difference in death or MI
• M – RCT
Extent of Ischemia and Presence of LV
Dysfunction
• Extent of ischemia
• important predictor of subsequent adverse outcomes
• number of vessels diseased
• LV function
• greatest survival benefits of CABG in impaired LV function
(ejection fraction<40%)
• Electrical substrate
Risks Associated with the Procedure

• General Considerations in CSA

• Pharmacologic therapy is the initial treatment and not revasc
• Severity of angina or symptoms has the significant role in
determining whether to revascularize or not
• patient’s preference and sociodemographics
• atypical symptoms may not necessarily improved with revasc
PCI
• Early outcome
• Angiographic success rate: 96%
• Rate of restenosis with DES <10%
• Late outcome
• Less repeat revasc in stenting than balloon angioplasty
PCI versus Medical
Therapy
• COURAGE
• P – Symptomati c SIHD, proximal angiographic CAD
• I – PCI + OMT versus OMT only, follow up 2.5-7years
• O – no difference in hospitalizati on for ACS/MACE
- Freedom from angina only lasted for 3 yrs in PCI group
- No difference in outcome with multi vessel CAD, low EF, CCS II or III or DM
• M–
PCI versus Medical
Therapy
• FAME
• P –SIHD
• I – FFR guided PCI versus angiographically directed PCI
• O – lower 2 year rate of death or MI with FFR guided strategy
• M – RCT

• FAME2
• P –SIHD with FFR of 0.8 in one or more stenotic coronary arteries
• I – OMT versus PCI + OMT
• O – 68% relative risk reduction in primary endpoint from 12.7% in medical to 4.3%
in
the PCI group. No significant difference in death or MI
• M – RCT
PCI versus Medical
Therapy
• FAME2 and COURAGE conclusion
• PCI reduces ischemic symptoms and the need for future revascularization
• Neither showed reduction in death or MI with PCI vs GDMT
• selective use (not routine) of FFR to guide PCI decision making for borderline
visual lesions (≈50% to 70% stenosis)
PCI versus Medical
Therapy
• Reasonable to pursue a strategy of initial medical therapy for most patients
with SIHD and CCS class I or II symptoms
• Reserve revascularization for pxs with more severe symptoms despite GDMT
or with high-risk criteria on noninvasive testing (e.g. inducible ischemia
involving a moderate or large territory of myocardium)
Patient Selection for PCI
• likelihood of successful catheter-based revascularization
• risk and potential consequences of acute failure of PCI
• likelihood of restenosis (clinical and angiographic factors)
• Need for complete revasc
PCI in Specific Subgroups with Stable CAD
• DM
• higher risk of complication due to
• altered vascular biologic response to balloon injury
• rapid progression of disease in nondilated segments
• procoagulant state, decreased fibrinolytic activity, increased
proliferation, and inflammation
• CABG is preferred
• LV dysfunction
PCI in Specific Subgroups with Stable CAD
• Women and older patients
• increased risk for complications in older, but no increased rate of
comorbid conditions (bleeding, worsening renal function)
• Renal dysfunction
• neither evidence of clinical bene t nor harm in patients with reduced
renal function who underwent PCI versus OMT
• decision to PCI should be individualized
• eGFR>60 better prognosis
• Previous CABG
Coronary Artery Bypass
Grafting
•
Goal
• prolong survival
• relieve angina
• improve quality of life
Coronary Artery Bypass
Grafting
•CORONARY
• P –patients for revascularization
• I – traditional CABG v OPCAB
• O – no difference in composite outcome of death, MI, stroke, or renal failure
requiring HD
• M – RCT

• OPCAB had lesser incidence of postoperative bleeding and AKI

Minimally Invasive Coronary Artery Bypass Surgery

• OFF-pump: OPCAB and MIDCAB (left anterior thoracotomy)

• Potential advantages: reduced postoperative discomfort,
minimize wound infection, and shorter recovery times, less
bleeding, thrombembolism, stroke, renal insufficiency,
myocardial stunning
• CABG with PCI
Minimally Invasive Coronary Artery Bypass Surgery

CORONARY TRIAL
• OPCAB (short-term outcome 30d) resulted in
• no difference in death (30 days), but worse after 1 yr
• no difference in major adverse CV effects (MACE)
• increased repeat revascularization
• less mechanical vent times
• decrease hospitalizations
• poorer graft patency
 Coronary Artery Bypass
•Grafting
Graft Patency (Distal Vasculature)
• Greatest patency when lumina of vessels distal to graft is >1.5mm (SVG graft optimal is >2mm)
in diameter, perfuse a large vascular bed and are free of atheroma obstructive >25% of vessel
lumen
• Occlusion (Vein graft)
• Early occlusion – 8-12% (prior to discharge)
• Within 1 year, 15 – 30%
• 2% per year up to 5th year post op
• 4% per year from 6th – 10th year post op

• IMA grafts are superior

• LIMA to LAD – benefits proven
• Bilateral IMA – Benefits are disputed due to higher post op complications including
bleeding, wound infection, prolonged ventilator support.

• Standard CABG: IMA to LAD then SVG to other vessels

• distal vasculature characteristic is impt because this is where you insert the graft
Progression of Disease in Native Arteries
• Bypassing an artery with minimal disease, even if initially successful, may be
harmful, who incur both a risk for graft closure and an increased risk for
accelerated obstruction of native vessels.

• Lesions in the native vessels that are long (>10mm) and >70% in diameter are
at increased risk for progressing to total occlusion
Coronary Artery Bypass
Grafting
• Measures to reduce risk for failure of grafts
• Aspirin 75 to 325mg daily for indefinite time
• benefit is lost if started >48 hours
• clopidogrel- less effective
• Statin (Target LDL <100mg/dL)
Patient Selection

• CABG is indicated, REGARDLESS OF SYMPTOMS

• CAD in whom survival is likely to be prolonged
• multivessel CAD in whom non-invasive testing suggests HIGH RISK
Surgical Outcomes and Long-term
Results
• Outcomes with CABG have generally remained stable or
have improved
• Operative mortality for CABG: 1.5-2%
 Coronary Artery Bypass
•Grafting
Most potent predictors of mortality after CABG
• Age
• Urgency of surgery
• Previous cardiac surgery
• LV Function
• Percentage stenosis of left main coronary artery
• Number of epicardial vessels with significant disease
Coronary Artery Bypass Grafting
Complications
• Myocardial Infarction
• 0 – 10% =, average 3.9%
• Criteria: elevation of cardiac troponin or a CK-MB level >10 x the
upper limit of normal with objective evidence of myocardial
dysfunction
• Predictors of periop MI
• Female
• severe perioperative angina pectoris
• severe stenosis of the left main coronary artery
• triple-vessel CAD
Coronary Artery Bypass Grafting
Complications
• Cerebrovascular complications
• Incidence of stroke 1.5-5%
• Silent brain injury detected by MRI 25-50% of patients after CABG
• Type I – major neurologic deficits, stupor, coma
- 6% early after CABG
- 33-83% with short term cognitive decline
• Type II – deterioration in intellectual function and memory
• Predictors of stroke
• older age
• comorbidities DM
• manipulation of the aorta
• CABG performed without CPB may be associated with reduced risk for stroke
Coronary Artery Bypass Grafting Complications
• Atrial Fibrillation
• Up to 40% primarily within 2-3days
• 2-4 fold increase in post op stroke
• Up to 80% resolve within 24hours without treatment other than agents to control rate
• Prophylaxis
• Preop statins
• Beta blockers – administered before and after CABG
• Amiodarone – considered for patients at high risk for AF
• Risk factors
• Older age, hypertension, previous AF, HF
• No benefit of extending anti arrhythmics beyond 1 week. mostly wil return to SR after
6 wks post op
Coronary Artery Bypass Grafting Complications
• Renal Dysfunction
• HD occurs in 0.5-1.0% after CABG
• Defined as creatinine >2.0mg/dL or an increase of >0.7mg/dL
• Predictors of dysfunction
• Age, diabetes, pre-existing renal dysfunction and HF
• N-acetylcysteine- NO BENEFIT
Relief of Angina
• Independent Predictors of Recurrence of Angina
• Female
• Obesity
• Lack of use of IMA as conduit
• Freedom from ischemic event
• 75% in 5 years,
• 50% in 10 years
• 15% in 15 years
Effects on Survival
• High risk criteria who are likely to sustain substantial survival benefit
• Left main CAD
• Single or double vessel CAD with pLAD disease
• LV systolic dysfunction
• Composite evaluation that indicates high risk
• Severity of symptoms, high risk exercise tolerance test, history of MI, presence of ST dep on resting
ECG
• The sicker the patient—based on the severity of symptoms or ischemia, age, the
number of vessels diseased, and the presence of LV dysfunction—the greater
the benefit of surgical over medical therapy on survival
Patients with Depressed LV Function
• CABG Patch trial
• confined to patients with an ejection fraction of 0.35 or less,
perioperative mortality was 3.5% for patients without clinical
signs of heart failure versus 7.7% for those with NYHA Classes I
to IV heart failure.
• Viability evaluation is a reasonable strategy when considering CABG
for patients with severe LV dysfunction
Patients with Depressed LV Function
• STITCH
• P – patients with EF <35%, NO left main or Class III Angina
• I – on-pump CABG v GDMT
• O –CABG had less composite MACE, but death any cause wasn't significant

Reduced hospitalization
• M – RCT
Patients with Depressed LV Function
• Myocardial stunning
• prolonged but temporary postischemic LV dysfunction without myocardial
necrosis
• Myocardial hibernation
• persistent LV dysfunction when myocardial perfusion is chronically reduced
(or repetitively stunned) but sufficient to maintain the viability of tissue
• prolonged hibernation maybe irreversible
• high mortality rate during medical therapy
• usual symptoms: dyspnea due to increased LVEDP
Detection of Myocardial hibernation
• Clues to distinguish viability
• angina
• absence of Q waves
• history of previous MI
• A severe reduction in the diastolic wall
thickness of dysfunctional LV segments is
indicative of scarring
• Akinetic or dyskinetic segments with
preserved diastolic wall thickness maybe
mixture of scarred and viable myocardium
Surgical Treatment in Special Group
• Women
• sicker, as defined by age, comorbid conditions, severity of angina, and
history of heart failure
• 2x higher In-hospital mortality and perioperative morbidity than men
• Older
• higher perioperative mortality and complication rates age > 70 years
• Renal Disease
• present in 50% undergoing CABG due to co morbids like DM, HPN with
LVH, LV dysfunction, anemia etc
• CABG is preferred if px is on dialysis
• DM
Impact of Combined Coronary Artery Disease and Peripheral
Vascular Disease
• Adverse prognosis due to greater atherosclerotic burden
• CAD and peripheral atherosclerosis tend to be older, more vascular disease
and end-organ damage
• Diffuse atheroembolism
• serious complication of CABG in patients with peripheral vascular disease
and aortic atherosclerosis
• major cause of perioperative death, stroke, neurocognitive dysfunction,
and multiorgan dysfunction after CABG
• Peripheral vascular disease is a strong marker of an adverse long-term
• CABG may have advantages over PCI
Carotid Artery Disease

• Frequency of carotid artery disease in CABG pxs

• 20%- 50% stenosis
• 6-12%- 80% stenosis
• Higher percentage in pxs with left main CAD
• Simultaneous or staged procedure of CABG and endartrectomy has been
demonstrated to be unequivocal so decision of simultaneous or staged should
be individualized
Management of Patients with Associated Vascular Disease

• Elective vascular sx
• can be postponed until cardiac condition is stable

• Unstable
• combined procedure is necessary in patients with both unstable CAD (PCI
can be performed) and an unstable vascular condition
Patients Requiring Reoperation

• Higher rate of mortality in reoperation

• first operation mortality
• 2.6% for urgent and 6% for emergency procedures
• Reoperation
• 7.4% urgent and 13.5% emergency
• Major indication for reoperation is late disease of saphenous vein graft
PCI vs CABG (Observational Studies)

• Higher repeat revascularization for PCI than CABG

• Survival benefit for CABG in LV dysfxn and proximal LAD stenosis
PCI vs CABG (Randomized Trials)

• Multivessel CAD and preserved ejection fraction

• CABG results in fewer repeat revascularizations and fewer symptoms
• CABG has no significant difference in survival when compared with
multivessel PCI
PCI vs CABG with Single Vessel Disease (Randomized Trials)

• Lausanne and the MASS trial

• P: Isolated proximal LAD disease
• I: PCI vs CABG
• O: rates of mortality and MI were similar
more frequent reintervention in patients treated with PCI
less recurrence of symptoms in CABG group
PCI vs CABG with Multivessel Disease (Randomized Trials)

• SYNTAX Trial
• P: High risk coronary anatomy 3VD or LM
• I: CABG vs PCI
• O: PCI has higher MACE, rate of MI, and repeat revasc
CABG has higher stroke events
Similar rate of death at 12 mos
Conclusion: CABG should remain the standard of care for complex coronary
lesions (high or intermediate SYNTAX), whereas for less complex CAD (low
SYNTAX) or left main CAD ( low or intermediate SYNTAX), PCI is acceptable
alternative

• CABG is better in DM andolder age

PCI versus CABG in DM
• BARI
• P – SIHD patients with DM, for revascularization
• I - PCI v CABG
• O - 34.5% mortality for PCI, 19.4% mortality for CABG
• M – rct

• BARI 2D
• P – DM and CAD
• I – prompt revascularization (PCI or CABG) versus delayed/no revasc
and OMT
• O –All patients: no difference in 5-year all cause mortality
• CABG had lower death, MI, stroke compared with OMT without
revascularization
• No difference between PCI and OMT (only 35% on DES)
• M - RCT
PCI versus CABG in DM
• FREEDOM
• P – DM patients with multivessel disease
• I – PCI (DES) v CABG
• O – reduction in all cause mortality, composite death or MI in CABG group
• M – RCT
•VA-CARDS (significantly underpowered)
• No difference in MACE between PCI and CABG
PCI versus CABG in DM
• Potential advantage of CABG over PCI
• bypass grafts to the mid–coronary vessel both treat the culprit
lesion (regardless of anatomic complexity) and may afford
prophylaxis against new proximal disease progression whereas
stents treat only suitable stenotic segments with no benefit
against the development of new disease
Choosing between Percutaneous Coronary Intervention,
Coronary Artery Bypass Surgery, and Medical Therapy

• Revascularization has not been shown to reduce the rate of death

or MI when used in patients with SIHD (with the exception of
surgery in patients meeting specific anatomic criteria)
• PCI or CABG? depends on
• extent and severity of ischemia
• severity of angina and functional impairment
Choosing between Percutaneous Coronary Intervention,
Coronary Artery Bypass Surgery, and Medical Therapy

• Single vessel disease

• PCI if suitable anatomy
• Multivessel disease
• left main CAD or severe triple-vessel CAD and LV dysfunction
• CABG best approach
• Rates of both MI and repeat revascularization were significantly higher in PCI
• PCI is reasonable for those who refuses sx
Need for complete revascularization

• Complete revascularization is an important goal in patients with LV

dysfunction and/or multivessel CAD
• CABG is the procedure of choice for complete revasc
• Factors to consider
• high quality team
• patient’s preference
• Advanced pxs age and comorbidity
• In young patients, PCI then CABG in the future may be preferable than double CABG
Summary of indications for coronary revascularization

• significant left main CAD, 3VD with prox LAD, LV dysfunction

(EF<50%), high risk on non invasive
• CABG in patients with LV dysfunction and multivessel CAD,
regardless of symptoms (even if with less defined benefits)
• PCI for single vessel for relief of symptoms
• Not high risk pxs- Sx PCI and OMT have similar survival
• PCI or CABG is highly efficacious in relieving symptoms for
patients with moderate to severe ischemic symptoms whose
condition is not controlled with medical therapy, even if they are
not in a high-risk subset
Revascularization to Improve Survival Compared with
OMT
Anatomic Setting COR AHA (2017) ESC (2014) PHA (2014)
UPLM, Complex CAD
CABG and PCI Heart Team approach IC IC
Calculate STS and SYNTAX IIa B -
UPLM
CABG Regardless of SYNTAX IB IB
PCI For SIHD when IIa B IB
- Low risk lesions, SYNTAX <22, ostial or trunk LM CAD
- When CABG has high risk for events (STS >5%)
3 Vessel Disease with or without pLAD
CABG Regardless of SYNTAX IB IA
- Complex 3-vessel CAD with SYNTAX >22 who IIa B -
are good candidates for CABG
PCI SYNTAX <22 IIb B IB
Revascularization to Improve Survival Compared with OMT
(Cont.)
Anatomic Setting COR AHA (2017) ESC (2014) PHA (2014)
2 vessel Disease with pLAD
CABG IB IB
PCI Uncertain benefit IIb B IC
2 vessel Disease without pLAD
CABG Extensive ischemia IIa B Iib C
Without extensive ischemia IIb C -
PCI Uncertain benefit IIb B IC
1 Vessel pLAD
CABG With LIMA for long term benefit (IB IIa B IA
PCI Uncertain benefit IIb B IA
1 vessel without pLAD
CABG Harm III B Iib C
PCI Harm III B IC
Revascularization to Improve Survival Compared with OMT
(Cont.)
Anatomic Setting COR AHA (2017) ESC (2014) PHA (2014)
LV Dysfunction
CABG EF 35-50% Iia B -
EF <35% without significnant LM IIb B IC
PCI Insufficient data Iib B Iia B
Survivors of SCD with presumed ischemia mediated VT
CABG IB IIa B
PCI IC Iia B
Multi-vessel Disease in Diabetic Patients
CABG Regardless of SYNTAX IB IA
PCI SYNTAX <22 Iib B Iia B
Multi-vessel Disease in CKD Patients
CABG With acceptable risk profile, expected to live >1year - Iia B
PCI High surgical risk, expected to live <1year - IIaB
Follow
up
Indications AHA (2012) ESC (2013) PHA
(2014)
Patients able to exercise
Standard ECG if with new or worsening symptoms not consistent with UA IB -
Exercise with MPI or Echo IB IC
Patients unable to exercise
Pharmacologic stress MPI or Echo IB IC
Pharmacologic stress CMR IIaB -
Irrespective of ability to exercise
Cardiac CTA (with or without revasc, stent <3mm, no known mod to severe calcification IIbB -
Cardiac CTA (with or without revasc, stent >3mm, known mod to severe calcification III -
Non invasive testing in patients with ASYMPTOMATIC SIHD
Exercise MPI, Echo or CMR q2years (silent ischemia or high risk) IIaC -
Exercise ECG q1year IIbC -
Exercise ECG (no prior evidence and NOT at high risk) IIbC -
Coronary Angiography -
After high risk PCI (UPLP) late (3-12months) angiography irrespective of symptoms - IIbC
Other Manifestations of CAD
Chest Pain with a Normal Coronary Arteriogram

• Syndrome X
• angina or angina-like chest discomfort with ECG evidence of ischemia but normal findings on
coronary arteriography
• increased risk for adverse outcome
• Causes
• Vascular (endothelial and microvascular) dysfunction
• coronary vasospasm
• myocardial metabolic abnormalities

• WISE
• two thirds of women with chest pain and other findings suggestive of SIHD had no critical coronary
stenoses detected with angiography
• evidence of endothelial and microvascular dysfunction
• coronary calcification on CT is significantly higher than that in normal controls (53% versus 20%) but
lower than that in patients with angina secondary to obstructive CAD (96%).
Chest Pain with a Normal Coronary Arteriogram

• Microvascular Dysfunction (Impaired Coronary Flow Reserve)

• abnormally decreased capacity to reduce coronary resistance and increase coronary flow in
response to stimuli such as exercise, adenosine, dipyridamole, and atrial pacing
• level of hsCRP appears to correlate with the severity of symptoms and burden of ischemic ECG
changes
• Evidence of Ischemia
• microvascular angina and impaired coronary flow reserve
• Abnormal Pain Perception
• Sensitive Heart Syndrome
• awareness of chest pain in response to stimuli such as arterial stretch or changes in heart rate,
rhythm, or contractility
• sensitive to intracardiac cath
Chest Pain with a Normal Coronary Arteriogram

• Clinical Features
• more frequent in women and premenopausal (in obstructive:more common in men and
postmenopausal)
• may have atypical symptoms
• PE and lab
• Normal resting ECG or nonspecific ST-T wave abnormalities
• 20% to 30% positive exercise test results
• Normal resting and exercise LV function (in obstructive CAD- abnormal in exercise)
• Not all have favorable prognosis
Chest Pain with a Normal Coronary Arteriogram

• Management depends on the cause

• ACE inhibitors
• for endothelial function, vascular remodeling, and sympathetic tone
• imipramine (50 mg daily)
• for somatic and visceral pain perception
• Non cardiac causes
• depends on the cause
Silent Myocardial Ischemia

• 1/3 of SCAD have silent ischemia with high prevalence in DM

• Ambulatory ECG
• Transient ST-segment depression of 0.1 mV or more that lasts longer than 30 seconds is a
rare finding in normal subjects
• symptomatic and asymptomatic ST-segment depression has a circadian rhythm and are
more common in the morning.
• Asymptomatic nocturnal ST-segment changes are almost invariably an indicator of
double- or triple-vessel CAD or left main coronary artery stenosis

• SPECT MPI
• symptomatic and silent ischemia, perfusion defects occur in the same myocardial regions during
symptomatic and asymptomatic episodes of ST-segment depression

• Pharmacologic agents that reduce or abolish episodes of symptomatic ischemia (e.g.,

nitrates, beta blockers, calcium antagonists) also reduce or abolish episodes of silent
ischemia.
Silent Myocardial Ischemia

• exercise ECG remains the most important screening test for significant
CAD
• If unable to exercise, MPI and pharmacologic vasodilator stress can be
used
• Mechanism
• overactive gating of afferent signals in the thalamus may reduce the cortical activation necessary for perception
of pain from the heart
• Autonomic neuropathy
• Increased endorphins
• Anti-inflammatory cytokines

• SWISS II
• PCI reduced mortality in silent ischemia vs OMT
Ischemic Cardiomyopathy

• CAD results in severe myocardial dysfunction, with clinical manifestations

often being indistinguishable from those of primary dilated
cardiomyopathy
• angina +ischemic cardiomyopathy= poor outcome
• Earlier symptoms: angina
• Late symptoms: heart failure
• Prognosis
• Medically treated is poor so consider revasc or transplant
• Poor prognosis
• multiple MI
• ventricular arrhythmias
• hibernating myocardium
• heart failure is caused by large segments of reversibly dysfunctional but viable myocardium,
may have a better prognosis and relief of heart failure symptoms after revascularization
Ischemic Cardiomyopathy

• If little or no viable myocardium: manage as DCMP

• Viable myocardium may derive a survival advantage with CABG but
these trials do not agree
• STITCH
• PARR-2:
• PET-guided management to determine myocardial viability did not
demonstrate advantage of revascularization
LV Aneurysm

• segment of the ventricular wall that exhibits paradoxical (dyskinetic)

systolic expansion
• scar tissue + viable myocardium / thin scar tissue also impair LV
function
• paradoxical expansion and loss of effective contraction
• 80%- anterolateral near apex
• 5-10%- posterior location
• ¾ of them are multivessel CAD
• often associated with TO LAD and poor collateral blood supply
• Mural thrombi are found in ½
• Embolic events occur early after MI
LV Aneurysm

• Detection
• persistent ST-segment elevations in the absence of chest pain
• bulge and marked calcification of the silhouette of the left ventricle on a CXR
• 2D echo
• True aneurysm
• wide neck
• almost never rupture
• False aneurysm
• narrow neck
• flow “in and out” of the aneurysm
• “to-and-fro” pattern with characteristic respiratory variation in the peak systolic velocity
• almost always has thrombus and often ruptures
• CMR
• preoperative assessment of LV shape, thinning, and resectability
LV Aneurysmectomy

• True LV aneurysms do not rupture

• CABG is frequently performed along with aneurysmectomy, in
patients in whom angina accompanies heart failure
• operative mortality rate: 3-8%
• STICH Trial
• surgical ventricular restoration (SVR) did not confer surgical benefit
MR secondary to CAD

• Acute MR
• Rupture of papillary muscles
• Chronic MR
• multifactorial
• Enlargement of the mitral annulus at end-systole is asymmetric
• posterior leaflet prolapse
• anterior leaflet tethering
• left atrium is enlarged after more than 6 months of MR
MR secondary to CAD

• Management
• MV replacement is is equivalent to repair in producing reverse LV remodeling
• Surgical revascularization and repair appear to be favorable over PCI in multivessel CAD with
significant mitral regurgitation
• CABG+MVR: 10% mortality
• CABG+MV repair: 6% mortality
• Predictors of early mortality
• need for replacement versus repair
• age
• comorbid conditions
• urgency of surgery
• LV function
• poorer in regurgitation from annular dilation or restrictive leaflet motion than in chordal or
papillary muscle rupture
• procedural risks associated with combined CABG and mitral valve repair may outweigh the benefit of
reduced mitral regurgitation in those at highest perioperative risk
• Cardiac arrhythmias
• dominant clinical manifestation of the disease
• Non atheromatous CAD
• most common is Prinzmetal angina
• congential abnormalities/anomalous origin
• Myocardial bridging
• systolic compression of the LAD coronary artery
• Connective Tissue Disorder
• Ehlers and Marfans: aortic and coronary dissection
• Hurler: coronary obstruction
• Homcysteinuria: coronary thrombosis
• Kawasaki: coronary aneurysms
• Spontaneous coronary dissection
• 75% women and associated with post partum
• Coronary vasculitis
• 20% rheumatoid arthritis
• SLE - vasculitis, immune complex–mediated endothelial damage, and coronary thrombosis from
antiphospholipid antibodies, as well as accelerated atheroclerosis
• APAS
• Takayasu arteritis
• angina, MI, and cardiac failure in patients younger than 40 years (average age 24yo)
• ostia or proximal segment involvement
• Post mediastinal irradiation
• adventitial scarring and medial hypertrophy with severe intimal atherosclerotic disease
• Cocaine
• alpha-adrenergic stimulation, which causes an increase in myocardial O2 demand and a reduction in
O2 supply because of coronary vasoconstriction