Unstable Angina

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UNSTABLE ANGINA S. NIRANJAN, MD, FACP, FCCP,
FACC Clinical Assistant Professor of
Medicine State University of New York at
Brooklyn Attending Cardiologist Coney Island
Hospital
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Definition Presence of one or more of the three
features, 1. Crescendo Angina- more severe,
prolonged, or frequent. 2.New onset (1 month)
brought on by minimal exertion. 3.Angina at rest
as well as with minimal exertion.
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• Prevalence
• 4 times the number of A/c ST elevation MI
• 1,300,000 patients with unstable angina or non ST
  elevation MI per year in the US.
• 3.1 million hospital days in 1991

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CLASSIFICATION OF UNSTABLE ANGINA SEVERITY C
LASS 1 NEW ONSET, SEVERE OR ACCELARATED
ANGINA ANGINA lt 2 MOS DURATION, SEVERE OR
OCCURING 3 OR MORE TIMES PER DAY, OR ANGINA
THAT IS DISTINCTLY MORE FRQUENT AND PPT BY
DISTINCTLY LESS EXERTION NO REST PAIN IN THE
LAST 2 MOS
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CLASS II ANGINA AT REST SUBACUTE PATIENTS
WITH ONE OR MORE EPISODES OF ANGINA AT REST
DURING THE PRECEDING MONTH BUT NOT WITHIN THE
LAST 48 HOURS CLASS III ANGINA AT REST
ACUTE PATIENTS WITH ONE OR MORE EPISODES AT REST
WITHIN THE PRECEDING 48 HOURS
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CLINICAL CIRCUMSTANCES
CLASS A SECONDARY UNSTABLE ANGINA Anemia,
infection, fever, hypotension thyrotoxicosis,
hypoxemia secondary to respiratory
failure CLASS B PRIMARY UNSTABLE
ANGINA Develops in the absence of extracardiac
condition CLASS C POST-INFARCTION ANGINA (within
two weeks of DOCUMENTED MI). Occurs in 20 of
A/c MIs
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• INTENSITY OF TREATMENT
• May be divided in to 3 groups depending on when
  it occurs
• ABSENCE OR MINIMAL TREATMENT OF CHRONIC
• STABLE ANGINA
• 2. OCCURING IN PRESENCE OF STANDARD RX FOR
• CHRONIC STABLE ANGINA (CONVENTIONAL DOSES OF
• BETA BLOSKERS, NITRATES, CCB)
• OCCURING DESPITE MAXIMALLY TOLERATED DOSES OF
• ALL 3 CATEGORIES OF ORAL RX , INCLUDING IV NTG

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Clinical features

• Chest discomfort similar in quality to effort
  induced angina, but more intense may last for
  30 minutes , may awaken from sleep.
• Abrupt reduction in threshold of physical
  activity
• Increase in frequency, severity, duration and
  development of rest angina or nocturnal angina
• New associated features- diaphoresis, nausea,
  vomiting, palpitation or dyspnea.
• Temporary or incomplete relief with S/L NTG

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Physical Examination

• Transient systolic murmur of MR, S3 and
  or S4 and or dyskinetic apical impulse.
• Above findings during or immediately after
  the ischemic episode
• These findings are nonspecific and may be
  present in chronic stable angina and in A/c MI.
• Presence of signs of CHF and hypotension
  suggest adverse prognosis.

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Elecrocardiogram

• Transient ST segment deviations and /or T
  wave inversions occur commonly.
• Dynamic shifts in ST segment and T wave
  inversions resolve partially when symptoms are
  relieved and are important markers of subsequent
  A/c MI and death.
• Transient inverted U waves
• ST segment changes in the anteroseptal
  leads suggest significant LAD stenosis and hence
  high risk group.
• Continuous EKG monitoring showed
  asymptomatic ST depression in 60 patients.

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Laboratory Tests

• Cardiac enzymes are not abnormally elevated.
• A/c phase reactants C-reactive protein and
  serum amyloid A protein are elevated
• Nonspecific indicators of tissue necrosis such
  as fever and leucocytosis are absent.
• Echocardiography may show wall motion abnormality.

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Cardiac imaging

• Especially important when ECG is normal, has
  nonspecific findings, obscured by LBBB or paced
  rhythm
• Sestamibi (Technetium-99m) enters myocardial
  cells proportional to regional blood flow and
  then binds to mitochondria and then imaged with a
  gamma camera
• Sestamibi is injected during chest pain and can
  be imaged in the nuclear Medicine Department
  later.

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PATHOPHYSIOLOGY Majority have severe obstructive
coronary atherosclerosis Episodes due to
reduction in myocardial O2 supply from
transient vasoconstriction and or platelet
thrombi. Firstly coronary sinus O2 saturation
decreases, then ST Segment depression, then
chest discomfort appears. Often caused by
reduction in O2 supply rather than demand.
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Mechanisms

• 1 Platelet aggregation
• Increase in sympathetic tone, hypercholesterolemi
  a, leucocyte activation, impaired fibrinolysis,
  increased levels of PAI-1 Thrombaxane A2
• 2 Thrombosis
• Suggested by increased levels of fibrin related
  antigen, D-dimer, tpa, tpa inhibitor-1,
  prothrombin fragments etc
• Intracoronary thrombus at coronary angiography.
• 3 Coronary constriction
• Vasomotor hyperactivity in the area of the
  atheroma by endothelin 1 thrombaxaneA2
  inhibiting the release of EDRF and prostacyclin

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MEDICAL THERAPY

• Antiplatelet agents
• Aspirin,Ticlopidine,Clopidogrel,11b/111a
  inhibitors
• Antithrombin therapy
• Unfractionated heparin,LMWH, Direct antithrombins
• Antianginal therapy
• Betablockers, nitrates, CCB,
• Coronary revascularisation

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MEDICAL THERAPY
BLOCKS PLATELET CYCLO-OXYGENASE BY IRREVERSIBLE
ACETYLATION , BLOCK FORMATION OF THROMBOXANE A 2
, A proaggregatory and Vasoconstrictor
substance. INSUFFICINET BLOCKADE OF PLATELET
ACTIVATION MEDIATED BY ADP, COLLAGEN,
THROMBIN NO INHIBITION OF PLATELET ADHESION

• ASPIRIN

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• TICLOPIDINE TICLID
• BLOCK ADP ,MEDIATED AGGREGATION
• TRANSFORMATION OF PLATELET FIBRINOGEN
• RECEPTORS INTO HIGH AFFNITY FORM
• ADJUNTIVE THERAPY WITH ASPIRIN FOR STENT
• PROBLEMS NEUTROPENIA
• TTP
• DIC ?

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• CLOPIDOGREL PLAVIX
• ADP DEPENDENT ACTIVATION OF GPIIB/IIIA
• COMPLEX AND EFFECTIVELY INHIBITS PLATELET
• AGGREGATION
• AFTER STENT WITH ASA FOR TWO WEEKS
• RECURRENT EVENTS ON ASA COMBINE WITH PLAVIX

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• GP IIB/IIIA INHIBITORS
• MURINE HUMAN CHIMERIC ANTIBODIES
• ABCIXIMAB RHEOPRO
• SYNTHETIC PEPTIDE
• EPTIFIBATIDE INTEGRELIN
• SYNTHETIC NON PEPTIDE
• TIROFIBAN - AGGRASTAT

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COMPETETIVE ANTAGONIST OF THE GP RECEPTOR ON
THE PLATELET SURFACE FOR ADHESIVE PROTEINS SUCH
AS FIBRINOGEN, VON WILLEBRAND FACTOR MAXIMALLY
INHIBIT THE FINAL COMMON PATHWAY INVOLVED
IN ACTIVATION ADHESION AGGREGATION
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CONSITENTLY REDUCED THE 30 DAY RISK
OF COMPOSITE END POINT OF DEATH MYOCARDIAL
INFARCTION NEED FOR REPEAT REVASCULARIZATION 22-
56 ADMINISTERED WITH IV HEPARIN/ASA/ GP
IIB.III A IN ADJUNCTIVE FASHION IN ACUTE CORONARY
INTERVENTION AS PRIMARY MEDICAL RX
ASA/HEPARIN/GP IIB/IIIA RESULTED IN SIGNIFICANT
REDUCTION IN THHE INCIDENCE OF MI / DEATH AT 7
AND 30 DAYS IN ACUTE CORNARY SYNDROME
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EARLY POTENT ANTI-PLATELET RX IN ACUTE CORONARY
SYNDROME PROVIDE BETTER OUT COME ISSUES DOSAGE
WITH MAXIMAL INHIBITION AND MINIMUM
BLEEDING DURATION OF THERAPY ROUTE IV gt
PO OPTIMAL COMBINATION ASA, HEPARIN,
LMWH THROMBOLYTICS
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• LMW HEPARIN
• BETTER BIO AVAILABILITY
• EASIER TO USE
• LOWER INCIDENCE OF BLEEDING
• LESS THROMBOCYTOPENIA
• LESS MONITORING
• ANTI X A CHROMOGENIC ASSAY
• INCREASED COST
• INABILITY TO MONITOR ANTI COAGULATION
• LEVEL CAN BE A PROBLEM DURING INVASIVE
• PROCEDURE

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DIRECT ANTI THROMBINS HIRUDIN, HIRULOG NOT
ACCEPTED AS PRIMARY ANTI THROMBOTIC RX IN ACUTE
CORONARY SYNDROMES WARFARIN EVIDENCE IS
INCONCLUSIVE REGARDING ADDING WARFARIN LONG TERM
FOR UNSTABLE ANGINA THROMBOLYSIS NO PLACE IN
NON ST ELEVATION ACUTE CORONARY SYNDROMES
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Incidence of the Failure of Medical Therapy
According to the Number of Risk Factors Present
on Admission. In patients treated
conservatively, the incidence of the failure of
medical therapy, which led to prompt coronary
angiography and revascularization, increased
substantially as the number of base-line risk
factors increased. These factors included the
presence of ST-segment depression on admission, a
history of angina, older age, a family history of
coronary artery disease, and the use of aspirin
or heparin. Plt0.001 for the comparison among the
groups. Adapted from Stone et al., (129) with the
permission of the publisher.
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Treatment Strategy for Patients Who Present with
Unstable Angina
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Criteria For High Risk On Noninvasive Testing
ECG gt 2MM ST DEPRRESSION gt1 MM ST DEPRESSION IN
STAGE ONE ST DEPRESSION MULTIPLE LEADS ST DEP
MORE THAN 5 MINS IN RECOVERY PHASE WORK LOAD LESS
THAN 4 METS OR LOW PMHR ABNORMAL BP
RESPONSE VENTRICULAR ARRYTHMIAS SPECT MULTIPLE
PERFUSION DEFECTS INCREASED TH203 LUNG
UPTAKE POST EXERCISE TRANSIENT LV DILATATION
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PATIENT IS BEING TREATED WITH ASA, METOPROLOL IV
HEPARIN, IV AGGRASTAT, IV TRIDIL 4 HOURS LATER
THE EKG SHOWS THIS WHAT DO YOU WANT TO DO ?
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