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					ACS   SAP   Asymptomatic

      CAD
                                Hospital

• Hx          Ventricular systolic dysfunction (LV/RV)



• EKG                                      Electrical instability


• PE
        Recurrent ischemia/infarct         •VT/VF
                             AC
        • Inhospital admission             •Heart Block
        • After discharged
                              S            •Atrial arrhythmia



                        Mechanical complication
                        •Myocardial rupture
                                                                    Before discharge
                        •MR
                        •VSD
                         หัวใจล้มเหลว

กล้ามเนื้อหัวใจขาดเลือดซ๊๊า             หัวใจเต้นผิดจังหวะ
                                        •VT/VF
• In-hospital admission                 •Heart Block
• After discharged            ACS       •Atrial arrhythmia


                  ภาวะแทรกซ้อนทาง mechanical
                  •Myocardial rupture
                  •MR
                  •VSD
                 Superficial
                  Erosion
Acute Coronary
  Syndrome
                  Ruptured
                 Fibrous Cap
Pathophysiology of ACS




Subtotal artery occlusion   Complete total occlusion


 Non ST elevation ACS          ST elevation ACS
    (UA/NSTEMI)                     (AMI)
             Structure of thrombus
          following plaque disruption
       UA/NSTEMI                     STEMI
Non-occlusive thrombus       Occlusive thrombus
(platelets, some fibrins) (platelets, fibrins, red cell)




                               Plaque core


   Intra-plaque thrombus
   (platelet dominated)
ST elevation ACS
Non ST elevation ACS
วินิจฉัย
- อาการเจ็บหน้าอก
- คลื่นไฟฟ้าหัวใจ (EKG)
- Cardiac enzyme
       Level




Time
                  Chest pain
                   Initial assesment Goal = 10 min
                Assess 12 lead ECG
            – Hx
            – PE
            – EKG and EKG monitoring
            – CXR
Non          Chronic       Possible     Definite
Cardiac      Stable        ACS          ACS
Diagnosis    Angina
• Treatment in ER
• Treatment at CCU and subCCU ward
• Treatment at general ward
• Prepare for discharge
Assessments and treatments to consider for
patients who present with ACS


        Initial general treatment (“MONA”)
  – Morphine 2-4 mg q 5-10 min
  – Oxygen 4 L/min
  – NTG sublingual or spray, followed by infusion for
    persistent chest pain
  – Aspirin 160 -325 mg chew and swallow or/and
    Clopidogrel 300mg oral
         Acute coronary syndromes
                                                 Aortic dissection

Esophageal reflux           Pneumothorax



        Chest pain
                                       Acute pulmonary embolism
          Myocarditis


                        Acute pericarditis
 Costochronditis                                  Psychosomatic
Treatment of the ACS: Perspective on the Future



      2 overlapping phases
        1. acute phase
        2. rapid stabilization of culprit lesions
•   Treatment in ER
•   Treatment at CCU and subCCU ward
•   Treatment at general ward
•   Prepare for discharge
Treatment of the ACS: Perspective on the Future
  1. acute phase in STE-ACS




      Fibrinolysis vs primary PCI


            “Time is muscle”
     Lives saved per 1000 patients
     with fibrinolytic therapy
40


30


20


10


0
       0-1   2-3 4-6   7-12
               Hours
                                  Door to Needle Time and Mortality
                                 20
                                                                                     18.1
                                 18
                                 16
                                                                         14.14
        In hospital              14
                                 12
                                                               10.3
       mortality (%)             10
                                  8
                                                       6.3
                                  6
                                         4.3
                                  4
                                  2
                                  0
                                        0-30          31-60   61-90      >90          no
                                                                                 thrombolysis
16   Door to Balloon Time and Mortality
                                               14.1
14
12
                       10
10                              9.1
8              7
6      5.6

4
2
0                                                                     Thai ACS registry
       <60   61-90   91-120   120-180      >180
       Acute Coronary Syndrome


             ST elevation >12 hr          •Conservative
             Or New LBBB                  •Primary PCI


                 <12 hr



Reperfusion therapy
 Primary PCI     Fibrinolytic (SK, tPA)
     • Fibrinolytic: door to needle time < 30 min
     • Primary PCI: door to dilatation time 90±30 min
 Clinical Markers of Reperfusion
        Marker                 Indicative of Reperfusion

   Symptom Evolution
                         •Prompt and persistent relief of chest
                         pain discomfort
ST Segment Deviation on •Return of ST segments to baseline ≥70
        ECG             % within 90 minutes
                         •Accelerated idioventricular rhythm
      Arrhythmias        •Hypotension / bradycardia
                         (Vagally mediated Bezold-Jarisch reflex)
                         Early peak (about 12 hours after
   CK MB Evaluation
                         symptom onset
                                      Primary PCI vs. Thrombolysis:
                                           Clinical Outcomes
                                                                                            PCI
                                                       P < 0.0001
               25                                                                           Thrombolytic therapy
                    Short-Term Outcomes
               20                                                                                      P < 0.0001

               15   P = 0.0002 P = 0.0003 P < 0.0001                P = 0.0004 P < 0.0001 P = 0.0032

               10
                5
Frequency, %




                0
                      Death     Death,   Non-fatal Recurrent           Total Haemorrhagic Major Death, Non-fatal
                               Excluding Myocardial Ischemia          Stroke    Stroke    Bleed Reinfarction,
                              SHOCK Data Infarction                                                or Stroke
               50                                      P < 0.0001
                    Long-Term Outcomes
               40
               30   P = 0.0019 P = 0.0053 P < 0.0001                                                   P < 0.0001

               20
               10                                                       -          -          -
                0
                      Death     Death,   Non-fatal Recurrent           Total Haemorrhagic Major Death, Non-fatal
                               Excluding Myocardial Ischemia          Stroke    Stroke    Bleed Reinfarction,
                              SHOCK Data Infarction                                                or Stroke

    Keeley et al. Lancet. 2003.
         Thrombolysis Remains an Important
         Reperfusion Strategy Worldwide

                                                            GRACE1       EHS2      NRMI 3-43
                                                            (n=5476)   (n=3438)   (n=153,486)


           Thrombolytic agent (%)                             45.0       35.1        52.0
           Catheterization (%)                                61.0       53.0         –
               PCI                                            44.4       40.4         –
               Primary PCI                                     –         20.7        48.1
           CABG (%)                                           5.0        3.4          –


          EHS=EuroHeart Survey


1. Goldberg RJ et al. Am J Cardiol 2004; 93: 288–293.
2. Hasdai D et al. Eur Heart J 2002; 23: 1190–1201.
3. Wiviott SD et al. J Am Coll Cardiol 2004; 44: 783–789.
         Importance of Time-to-Treatment:
            Mortality at 6 Months in 10 RCT’s
                 Meta-analysis

           Early      Intermediate      Late
           <2 h           2-4 h         >4 h
%   16                                       14.6
    14
    12
    10
                               7.3                       Primary PCI
    8                                  6.7
                         6.1                             Thrombolysis
    6     5.1   5.4

    4
    2
         n=414n=424     n=512n=523    n=297n=315
    0


                                                    Zijlstra at al. EHJ 2002
                    30-day mortality in major
                 acute myocardial infarction trials

                P=0.001        P=NS         P=NS                 P=NS

                7.3           7.2   7.5
                                           6.6   6.8
Mortality (%)




                      6.3                                       6.2     6.2
                              SK< tPA, rPA,TNK


                SK    rt-PA   rt-PA r-PA   rt-PA n-PA          rt-PA TNK

                GUSTO I       GUSTO III     InTIME-2            ASSENT-2
                 (1993)        (1997)         (2000)             (1999)
                                                       *Lower major bleeds for TNK-tPA
                                                          (4.7% vs 5.9%; P=0.0002).
Strategies for improving pharmacological
                reperfusion


             Improved
            antiplatelet                  Improved
             co-therapy                  fibrinolytic
                                            Agents
        i.v. glycoprotein IIb/IIIa         convenience
                 inhibitors          (tenecteplase, reteplase)

               clopidogrel             risk of major bleeds
                                          (tenecteplase)
Clopidogrel Reduced Primary Endpoint by 36%

                    Clopidogrel Placebo     Odds ratio
                     (n=1752) (n=1739)       (95% CI)     p value

Primary composite endpoint (%)
  TFG 0/1, MI or death 15.0       21.7    0.64 (0.530.76) <0.001

Individual components of primary endpoint (%)
  TFG 0/1               11.7       18.4 0.59 (0.480.72) <0.001
  Recurrent MI           2.5        3.6 0.70 (0.471.04) 0.08
  Death                  2.6        2.2 1.17 (0.751.82) 0.49
Strategies for improving pharmacological
reperfusion
               Improved
              antiplatelet                       Improved
               co-therapy                       fibrinolytic
                                                   Agents
          i.v. glycoprotein IIb/IIIa            convenience
                   inhibitors             (tenecteplase, reteplase)

                 clopidogrel                 risk of major bleeds
                                                (tenecteplase)

                               Improved
                             antithrombotic
                               co-therapy

                          Direct thrombin inhibitors
                             (hirudin, bivalirudin)

                                    LMWH
                                 (enoxaparin)
                                        Primary End Point (ITT)
                                         Death or Nonfatal MI
                        15

                                                                       UFH
Primary End Point (%)




                        12                                                         12.0%

                                                                      17% RRR
                                                                                       9.9%
                        9
                                                                      ENOX

                                                                   Relative Risk
                        6
                                                                 0.83 (0.77 to 0.90)
                                                                     P<0.0001
                        3

                                 Lost to follow up = 3
                        0
                             0   5        10        15      20        25          30
                                                     Days
 PCI after fibrinolysis


• Failed fibrinolysis
  – PCI immediately (rescue PCI)




                              JACC 2006, January
Kaplan-Meier survival curves for patients randomly
assigned to rescue PCI or conservative


  Survival %
    1.0
                                         PCI
   0.9

                                      No PCI
   0.8


   0.7


   0.6
         0           24                    62 weeks



                               Am J Heart 2000;139:1046-53
      PCI after fibrinolysis

• Failed fibrinolysis
  – PCI immediately
  – Hours to days after failed fibrinolysis No benefit
• Successful fibinolysis
  – PCI immediately Not recommend
  – Hours to days after succesful fibrinolysis
                                     Recommend


                                      JACC 2006, January
NSTEACS
Non ST elevation ACS

                             Antithrombin
  fibrinolytic                UFH, LMWH




                              Stabilized
    Severe stenosis
   Subtotal occlusion
                             ASA, clopidogrel,
             Antiplatelets   G2b3a inhibitors
NSTEACS


          PCI




          ยา
Treatment of the ACS: Perspective on the Future
  1. acute phase in NSTE-ACS




                        Routine
                          vs
             Selective invasive strategies
Main Outcomes in Trials of Routine vs Selective Management of NSTE-ACS
     ( TIMI iiiB, VANQWISH, MATE, FRISC ii, TACTICS, VINO, RITA 3)


    10
                                                   9.4
     9                                           Selective (Nonfatal MI)
     8                                            Routine (Non fatal MI)
                                                   7.3
     7                             6.6              Selective (Mortality)
     6                                             6
                                                   5.5
     5                             4.9
                                                 Routine (Mortality)
                 3.7              3.8
     4
                                  3.8
     3            3

     2            1.8
     1            1.1

     0
           In-hospital    After hospital       Overall
                           discharge
                                                 JAMA 2005:293:2908-17
Main Outcomes in Trials of Routine vs Selective Management of NSTE-ACS
     ( TIMI iiiB, VANQWISH, MATE, FRISC ii, TACTICS, VINO, RITA 3)




   “Early Hazard but followed by
    later benefit in routine invasive”




                                                 JAMA 2005:293:2908-17
Early invasive strategy in NSTE-ACS
      •   Recurrent ischemic
      •   Elevated troponin level
      •   New ST segment depression
      •   CHF, new or worsening MR
      •   Depressed LV function
      •   Hemodynamic instability
      •   Sustained VT
      •   PCI in 6 months
      •   Prior CABG

                                  JACC 2006, January
Treatment of the ACS: Perspective on the Future



    2. rapid stabilization of culprit lesions
      - to attenuate plaque thrombogenicity.
      - to rapidly control of the disease process.
    Statin, ACE-I, antiplatelets, BB
      - to prevent recurrence.
                                                PROVE-IT-TIMI-22

                                      0.1                            LDL >70 mg/dl, CRP>2 mg/L
Recurrent MI or Coronary Death (%)




                                     0.08
                                                                     LDL >70 mg/dl, CRP<2 mg/L
                                     0.06                            LDL <70 mg/dl, CRP>2 mg/L

                                                                     LDL <70 mg/dl, CRP<2 mg/L
                                     0.04


                                     0.02


                                     0.00

                                            0                      2.5 y


                                                                             NEJM 2005;352:20-8
                  4000


                  3000          ACE-I
Number of death                 Placebo

                  2000


                  1000


                    0
                         0-1 D    2-7D    8-30D   Total

   Lives saved            1.9      2.2    0.9     4.8
   per 1000
                    Beta-Blocker
Early use

Pre-thrombolytic era
• infarct size, cardiac rupture, ventricular function
•Prevent life threatening ventricular arrhythmia.

 6 lives saved per 1000 patients treated with beta-blocker

Thrombolytic era (TIMI IIB)
• Recurrent ischemia & reinfarction (non-fatal)
               Beta-Blocker
Long term use
(timolol,metoprolol,propanolol,atenolol)
• 20-25% mortality and reinfarction rates


Conclusion
AMI patient who do not have contraindication should
be treated within 24 hours from the onset with IV or
oral beta-blocker and the treatment should be
continued for at least 2-3 years or longer.
        Therapy for Acute MI: Effect on Mortality

Therapy             Pt (no.)                          P
Aspirin              18,773                         <0.001
Thrombolysis         58,600                         <0.001
b blocker            28,970                          0.02
b blocker (post)     24,298                         <0.001
ACE-I               100,963                          0.006
ACE-I,  EF           5,986                         <0.001

Statins (post MI)   13,673                          <0.001
Statins (ACS)        3,086                          <0.05


                               0.5   1.0      1.5
•   Treatment in ER
•   Treatment at CCU and subCCU ward
•   Treatment at general ward
•   Prepare for discharge
Post ACS risk stratification
SYMPTOMS
               Prognosis
  12-Year
Survival (%)

      70
      60
      50                                        LVEF
      40                                         (%)
      30
      20                                  >50
      10                               35-40
                                    <35
       0
               1     2       3

           No of Diseased vessels

                                      Circulation 1994;90:2645
                               Prognosis


                  100
                   80

5-Year Survival    60
      (%)          40                                           4
                   20                                     3
                                                     2        Exercise Tolerance
                    0                                          (Stage of Bruce
                         <1      1=2      >2    >1                Protocol)

                        ST Segment Depression
                               (mm)


                                                         J Am Coll Cardiol 1984;3:772
       Post STEMI

• Post MI angina         Pre-hospital stress test discharge D5-7
• VT,VF after 48 hrs
• LVEF <40%

                       Positive         Negative

                       Maximal stress test 4-6 wks after discharge



                          Positive       Negative



                                     Medical treatment
Revascularization
                            Revascularization
     Percutaneous coronary intervention (PCI)
      Coronary Artery Bypass Graft ( CABG)
   is a medical procedure that opens up
    blocked or narrowed blood vessels
    without surgery.
               ABCDE

A- antiplatelets, ACE-I
B- beta-blocker, blood pressure control
C- cholesterol lowering, cigarette smoking
  cessation
D- diet, diabetes management
E- exercise
       Ventricular systolic dysfunction (LV/RV)



                                     Electrical instability
Recurrent ischemia/infarct           •VT/VF
                                     •Heart Block
• Inhospital admission   ACS         •Atrial arrhythmia
• After discharged

                 Mechanical complication
                 •Myocardial rupture
                 •MR
                 •VSD
Angina pain




              Nitrates


              Beta-blockers


              Calcium channel blockers
      antianginal therapy for angina patients:

• Hemodynamic agents are first line drugs (ACC/AHA and
  ESC recommendations)

• Metabolic drugs are potentially effective and can be
  used as second line group of drugs, especially in
  combination with hemodynamic agents (ESC
  recommendations)
                Results of Polish study
          500    485
                       457                            465
          450                             427               423
                                                381
          400

          350
                 P=0.05
                                                                       Met+TMZ
          300                             P<0.01      P<0.01           Met+P
seconds




          250

          200

          150

          100                 P=0.01
                                                                     P<0.01
           50                 9.7    9                               2.1   3
            0
                Duration of   METs       Time to ST   Time to      Number of
                   EST                   depression   angina      angina/week


                                                 Coronary artery disease 12:s25-28;2001
   Management of atherosclerosis


Control of risk factors
Diet, Exercise
Smoking cessation

   General           High
                   Preventive therapy
                                  No    Stable
                   ASA,Statin,ACE-I                       ACS
  prevention          risk   symptom    angina
                                        Treatment
                                        NTG,bB,CCB,FFA inh,
                                        PCI or CABG

                                                    Treatment
                                                    UFH/LMWH
                                                    ASA+clopidogrel
                                                    GP2b3a inh
                                                    PCI, Fibrinolytic
Rehabilitation

				
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