.UNSTABLE ANGINA AND NSTEMI
UNSTABLE ANGINA.
Defined as stable angina pectoris that
changes or worsens.
It is a very dangerous condition
Results from disruption of coronary
arterial plaque with superimposed partial thrombosis and/or vasospasm. (fig.1.)
When the plaque in the artery breaks
open, thrombus forms, This causes larger block
Thrombus may form, partly dissolve and
may form again.
Anginal pain occurs each time the
thrombus blocks the artery.
Frequently evolves into acute MI -if
thrombus grows large enough to completely block the artery, it causes MI.
Importance
Unstable
angina is a medical emergency .If unchecked evolves into acute Myocardial
infarct-even if symptoms of UA lessen or disappear risk remains.
Sudden rupture of a plaque causes
rapid accumulation of platelets at the site of rupture and rapid obstruction of
blood flow in the coronary artery .As a result, symptoms occur suddenly in
unexpected unpredictable way. Unchecked, the accumulation of platelets and
obstruction to blood flow can result in myocardial infarction.. Immediate
medical care is a must.
In
patients with myocardial ischemic symptoms ,but no elevation in troponin or
CK-MB, Unstable angina considered to be present,
ECG changes may or may not be present (ST
depression, transient elevation or new T wave inversion)
In (UA) NSTEMI cardiac biomarkers are normal but in
STEMI it is elevated.
Ways of manifestations
·
Angina of recent onset (within the prior 4-6 wks )brought on low work load
·
Angina occurring at rest or with minimal exertion or during sleep.
·
Angina occurring without any trigger
·
Lasts more than 10 min or persists longer than usual
·
It shows crescendo pattern
(Distinctly more severe, prolonged or more frequent than before)
·
Accelerated angina where patients of stable angina get angina more
frequently and lasting longer(sudden worsening of stable angina)
·
If
an episode of unstable angina is the first instance of angina ,it is called
New onset unstable angina.
·
Post MI angina –(24hrs -2wks) after MI (included)
·
May show acute ST elevation or depression or no permanent change.
·
Pain often resistant to
nitroglycerine.
·
New onset angina: First
attack of angina; the period of 6 wks after the 1st attack is
unstable/dangerous; Therefore patient with new onset angina even if only
exertional in nature should be treated as if they have a potentially unstable lesion
·
Occurs at unexpected unpredictable times
Significance of recognizing unstable
angina
It
is a dangerous condition often heralding impending MI. Such patients can
suddenly die.
Clinically;
Intermediate
between chronic stable (exertional) angina and acute myocardial infarction.
PATHOPHYSIOLOGY OF UNSTABLE ANGINA (fig 2
This is important in understanding management
strategies
UA
and evolving MI share a common pathophysiological mechanism
4 Factors involved
Supply-demand
mismatch
1Plaque
disruption or rupture
2Thrombosis
and Vasoconstriction
3Cyclical
flow
1.
.
Supply-demand mismatch
Mismatch
resulting from excessive demand or inadequate supply of oxygen
2. Plaque disruption
·
Inside
the atherosclerotic plaque, foam cells -lipid laden macrophages
accumulate.
Fig1..Picture
of atherosclerosis formation inside coronary
vessel
·
LDL
cholesterol within foam cells is chemotactic and cytotoxic.
·
Metallo
protease from macrophages and elastases from neutrophils produced within the
plaque cause thinning of fibrous cap
·
These
plaques are soft and friable
·
Hemodynamic
shearing force and plaque instability results in plaque rupture
·
The
degree of plaque rupture may be mild, moderate or severe.
Mild-non
occlusive /asymptomatic
Moderate
and severe plaques- causes unstable angina or acute infarct
·
Plaque
rupture exposes the thrombogenic lipid core; Thrombus formation occurs over the
plaque surface
·
Plaques found in unstable angina:-
Have thinner
fibrous cap and a large lipid core;
Are
more widespread and severe than in Stable angina
The
edge /shoulder region of the plaque is most vulnerable for rupture
The plaque
does not surround the entire circumference of the artery (eccentric);
Figure2..Pathophysiology of
unstable angina
3. Thrombus formation and vaso constriction
Note :
·
ACS
results from sudden thrombotic formation ,not from gradual plaque accumulation
·
At
the site of plaque rupture (fissure)platelets aggregate and thrombus forms
Large
fissure can causes occlusive thrombus(Qwave MI)
Small
fissure - non occlusive thrombus and causes unstable angina.
·
When thrombus does not cause complete vessel
occlusion, unstable angina results.Hence
In this condition there is no myocardial necrosis and so no rise in enzymes and
biomarkers
·
Thrombus formation is
also associated with vaso spasm induced by endothelial damage
·
Platelet aggregation also
causes release of vaso constrictors serotonin and thromboxane
·
Non
occlusive thrombus of unstable angina can become occlusive transiently or
persistently
In
such situation one of the following occurs
Recurrent
unstable angina or NQMI or Qwave infarct
This
depends upon
Duration
of occlusion
Presence
of collaterals
Area
of myocardium perfused.
Note:
The lesion being eccentric, the normal segment in the artery containing
smooth muscles is capable of contracting and reducing the lumen still further.
(This vasospasm cannot take place in concentric lesions with much more fibrosis
all around)
·
Thrombus
of Unstable angina is platelet rich:
this has a bearing on treatment.
4. Cyclic flow
Clot
formation is a dynamic process; degree of obstruction may suddenly increase or
regress in UA
Clot forms, enlarges, may chips
off and embolise
Clots
may form, dissolve and form again
Overtime, this cyclical clot
formation and lysis associated with vasospasm and
resistance of microvascular bed causes cyclical occlusion and flow.
CLINICAL TERMINOLGY (Text box1.)
Clinical spectrum of coronary disease and
place of unstable Angina
Unstable angina belongs to the clinical spectrum called acute coronary
syndrome. It can be considered as a subset of ACS. (Text box1)
ECG wise
differentiation in the above 3 groups shown below ,helps to guide their
diagnosis and management.
Above Flow chart shows Acute coronary syndrome showing the types
Unstable angina and NSTEMI are considered together
often, since these patients are difficult to distinguish from one another
clinically and -ECG -wise.-have similar early diagnosis and therapeutic
approach.( AHA guideline 2014)
| NSTEMI |
definition
·
The evaluation and management are almost similar for all 3 components of Acute coronary
syndrome.
Diagnosis and investigations;
§ Assessment of the chest pain.
§ Since MI pain is similar rule out MI
by following tests
§ Serial measurement of biochemical
markers troponin I, T,CK-MB.
§ C-Reactive proteins, Amyloid-a
protein as serum markers of inflammation
§ Evaluation of the ECG.
ECG;
§ In unstable angina or partial
thickness MI, No Q forms.
§ ST/T wave changes may occur; ST
depression, transient ST elevation, T inversion.
§ T wave changes are sometimes
prolonged.
§
Continuous
ECG monitoring is advised
1.
To
detect arrhythmias though rare.
2.
To
look for evidence of recurrent ischemia (ST change).
Angioscopy /Intravascular
ultrasound; shows
“White” platelet rich thrombi -of
unstable angina as opposed to Red
thrombi
In
STEMI.
Troponins:
In unstable angina there is no release of
enzymes or biomarkers of
Myocardial
necrosis. However serial cardiac biomarkers assessment is to be done along with
other lab tests for ACS.
Unstable
angina shares the investigations and treatment of Non Q MI and Q wave MI
Unstable
angina and acute MI may coexist
ECG stress
test, Echo stress test, Nuclear stress test, cardiac cath &angio help in
ruling out MI
TREATMENT OF
UNSTABLE ANGINA (Text box 1&2)
Learning point:
Text box 2. Approach to a case of Ischemic chest pain-An outline
Selection of treatment strategy:
Invasive vs conservative(chart 27.4.2)
Selection
is done on the basis of risk stratification; always choice should be
individualised
High risk cases: Plan invasive therapy Table 27.4.1
Concurrently administering
antiplatelet and anticoagulants as indicated
Low risk cases: Initial
conservative strategy: table 27.4.1
Coronary
angiography is deferred and is guided by ischemia
Repeated
ischemia and high risk stress test despite medical therapy, being taken as
indication for subsequent angiography
This
is accompanied by tests to evaluate LV function
Early conservative versus invasive strategies
;(Always
choice should be individualized
)
.
HIGH RISK
|
LOW RISK
|
|
Clinical
|
Post
infarct angina
Recurrent/
prolonged painat rest
Heart
failure
Hemodynamically
unstable
|
No
history of MI
Rapid
resolution of symptoms
|
ECG
|
ST
depression
Transient
ST elevation
Persistent
deep T wave inversion
|
Minor
or no ECG changes
|
Enzymes
|
Troponin
T>o.2 µg/ml
|
Trponin
I,negative
|
TABLE . Criteria for high risk
and low risk cases Recent advances-Risk stratification includes TIMI and
GRACE scores
Since cardiac biomarkers may not be detectable
for upto 12 hrs after presentation, UA and STEMI remain indistinguishable at
initial evaluation.
GOAL OF THERAPY
1.Relieve
symptoms,by reducing myocardial demand &halting thrombus formation
2.prevent
acute MI /DEATH -by reperfusing the ischemic tissue
TREATMENT OF UNSTABLE ANGINA
COMPRISES OF
I.
Initial medical
treatment (Emergency Anti ischemic therapy)
II.
Urgent Invasive
therapy in high risk cases
III.
Conservative therapy for Low risk cases
IV. Specific
Antithrombotic and antiplatelet therapy along with ongoing risk stratification and use of invasive procedures Fig 2
II.
Early invasive therapy in
high risk cases with revascularisation
Coronary
angiography as soon as possible
Angio
is usually followed by ( revascularization)- PCI or coronary bypass surgery,
depending
upon angio findings-depending upon location and number of blocks
In some centers coronary
angiography and revascularization is performed within 24 hrs-
Contra
indication for Angioplasty:active bleeding ,comorbidities
III.Conservative therapy :
In
low risk and some intermediate risk patients:
Patient
is given medical therapy and if response is poor proceeded with exercise test
or coronary angio to decide about PCI or CABG.
.
INITIAL MEDICAL TREATMENT OF
UNSTABLE ANGINA COMPRISES OF
1.Emergency therapy- to relieve the symptom(primary
therapeutic measures)
This
involves chewing of aspirin 300mg immediately. Chewing accelerates absorption
Immediately
because platelet aggregation starts within 30 minutes in ACS..
2.
urgent hospitalization Various guidelines are available to identify very low risk patients in whom admission can
be avoided.
3.
Supplemental O2 as indicated after pulse oximetry
4. Continuous
ECG monitoring
5.Another
2 important initial drugs are Nitrates and B blockers
(if
not contra indicated.)
Drugs used for initial management
- Aspirin
- Thienopyridines(clopidogrel,prasugrel)
- Heparin
- GPIIb/IIIa inhibitors
- Beta blockers
- Nitrates
- For all these drugs Contra indications should be
considered before administration)
Antiplatelet agents for initial
management fig .3
ASPIRIN
- After emergency administration of Aspirin,75 mg of
aspirin is to be continued indefinitely
THIENO
PYRIDINES
Clopidogrel
Recommended
when intolerant to Aspirin and also in
combination with it.
But
clopidogrel though more efficacious has increased risk of bleeding.
Prasugrel
- Can use as alternative to clopidogrel
- More potent but higher risk of bleeding.
- Cannot be
used for dual platelelet regimen.
- Because of potential harm,used only sparingly.
- Unproven for use in STEMI
NON
THIENOPYRIDINE P2Y12 inhibitors
Ticagrelor
- Indicated as 2nd antiplatelet
agent in addition to low dose
aspirin
- Proved to
be of use inSTEMI
- This is a novel oral P2Y12 inhibitor
GPIIB/IIIA inhibitors
·
Main
disadvantage – only Intrvenously usable
·
Currently
available agents-Abciximab,Eptifibatide,triofiban
·
Only
Eptifibatide and triofiban are shown to be beneficial in patients treated with
medical management alone.
Anticoagulants for initial management fig 3
Heparin
Two
forms :Unfractionated Heparin(UFH),LMWH-Low molecular weight Heparin
Enoxaparin-LMWH-benefits:Less
cost,less bleeding,less incidence of thrombocytopenia.
Demerit-anticoagulation activity cannot be measured during PCI
Fondaparinux: more suitable ,more potent But
causes increased rate of guiding catheter thrombus
But
switching from one agent to another does
not cause clinical benefit,causes excess bleeding.Fondaparinux should be avoided in patients with stage 4 Chronic kidney disease.
Dosage
must be adjusted in patients with renal impirement.
Bivalirudin: Is a direct thrombin inhibitor-alternative to Heparin
But
is costlier,has high rate of bleeding.
Not
recommended for routine use in NSTEMI
Drugs
to reduce mortality/measures to protect the ischemic myocardium
Beta Blockers:
Decrease
incidence of Symptoms and development of MI by-
reducing
the heart rate,BP and cardiac contractility.
But
contra indications have to be taken into consideration before use.
Oral
beta blockers have to be used.
Nitrates
IV
nitrates are useful in reducing chest pain,in hypertensionand heart failure.
But
they do not show long term benefit.
Other drugs
ACE
Inhibitors-especially
useful in cases of large anterior wall infarct with LV dysfunction
Indicated
in Congestive failure,DM,Hypertension
Started
within 24 hrs of admission and titrated for BP effect.
Statins
Show
mortality benefit: early initiation reduces adverse events within short time;
Can
start this agent within 24-96 hrs of admission. if started at hospital discharge it improves adherence; Statins
(Atorvastatin/Simvastatin/lovastatin) used regardless of lipid level in the
patient.:Also beneficial in secondary prevention.
Safety
Alert :statins
can result in myopathy/Rhabdomyolysis-induce kidney failure.
Frequently
Creatinine kinase activity is to be
measured.
Drugs
having no role in Unstable Angina
1.Fibrinolytics
2.Calcium channel blockers.3.
Antibiotics against Chlamydia pneumonia
Fig 3.Therapeutic approaches in Unstable angina pectoris
INTERVENTIONAL THERAPY: REVASCULARIZATION/ SURGERY
INDICATIONS
Drug
therapy mainly lowers the demand, rather
than improving the supply and so does not completely remove the symptoms. Hence invasive therapy as and when indicated-specially in high risk patients
(Refer chapter on revascularization for details
on PCI,Stent and related topics)
IV .Long term treatment for coronary artery
disease
1. Aspirin low dose -life long;
prevents platelet aggregation
2. 2.Ticagrelor-platlet aggregation
inhibitor.
3. Beta blockers
4. Lipid lowering agents
Caution: Ticagrelor is more rapid in onset
and more potent inhibitor of platelets than clopidogrel.It is direct acting
inhibitor of adenosine diphosphate receptorP2Y12.
But
it can cause serious life threatening bleeding.
V. CAD risk
factor treatment
Medication
for hypertension/diabetes
VI. Life
style modifications
A)
Healthy
diet: DASH diet
B)
Regular
exercise
C)
Quitting
smoking
D)
Weight
reduction in obese
E)
Minimising
alcohol intake
---
Difference in
treatment in three types of angina.
In
stable angina Coronary flow is limited; O2 demand is not met with.
Aim
of treatment is to reduce O2demand with Vasodilators and bblockers.
In
unstable angina –same drugs with addition of aspirin and heparin to inhibit
platelet aggregation and thrombosis which is the main pathology
In variant angina aim is to
reverse coronary spasm
Pathophysiologically
In stable angina atheroma is protected by a fibrous cap.This cap ruptures in
Unstable angina
|
Reason : in UA ,thrombus is often intra plaque and luminal projection is not common, and thrombolytic agents have limited area to act. UA thrombus is predominantly white and platelet rich.,Over this thin fibrin coat forms. Thrombolytics are fibrinolytics and they cannot lyse the platelet rich clot If they lyse the thin fibrin coat , they themselves can trigger fresh thrombus formation
Different combination of Aspirin,clopidogrel,
prasugrel,Ticagrelor&GPIIbIIa inhibitors are put into use.
Eptifibatide,tirofiban
are other drugs included.(parenteral drugs)
UNSTABLE
ANGINA- ABSTRACT
·
Angina
experienced at rest is unstable angina
·
It
has unpredictable onset of pain
·
Unstable
angina does not last as long as MI pain and does not damage the myocardium
usually
·
Unstable
angina needs to be diagnosed early and accurately.
·
Underlying
pathology is usually an ulcerated
plaque, with local platelet aggregation
and without complete vessel obstruction
·
Sometimes
clot may be temporary, pain resolves when clot dissolves resuming blood flow.
·
Diagnosis-by
history and ECG changes showing no persistent ST elevation or blood showing no raised troponin levels
·
In
high risk groups-ECG changes and raised troponin levels may occur.
·
Management depends upon patients risk profile
·
Stress testing may help in diagnosis and directing
future treatment
·
New
medical management to stabilize high
risk patients includes low molecular wt heparin,
Clopidogrel
and triofiban via an infusion.
·
After
initial stabilisation early angiography followed by coronary intervention can
significantly improve the outcome in refractory angina and Hemodynamically
unstable cases.
·
Long
term risk factor management and drug therapy controls symptoms and reduces future
CVS events.
…………..
-
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