Quinn Capers, IV, MD

Transcription

1 Heart Attacks Mended Hearts Presentation, January, 2017 Quinn Capers, IV, MD Associate Professor of Medicine (Cardiovascular Medicine) Director, Transradial Coronary Interventions Division of Cardiovascular Medicine

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3 Acute Coronary Syndromes Definition Life-threatening episodes of abrupt decrease in coronary blood flow in the patient with coronary atherosclerotic heart disease Continuum (clinical): from unstable angina to ST segment elevation myocardial infarction (STEMI) Clinical continuum correlates with degree of coronary artery obstruction, from partial to complete.

4 Coronary Atherosclerosis: Vascular Biology Stable angina Unstable angina/ NSTEMI STEMI

5 Acute Coronary Syndromes Biological/Clinical Correlation Stable plaque: Chronic, stable exertional angina pectoris Low inflammatory state Chronic coronary syndromes Unstable or vulnerable plaque: Unstable angina, acute MI High systemic inflammatory state (CRP, ESR, IL1) Acute coronary syndromes

6 1: Excess circulating LDL cholesterol gets subendothelial and becomes oxidized, stimulating an inflammatory response.

7 2: Circulating inflammatory cells are attracted to the subendothelial compartment to participate in the inflammation

8 3: Once in the subendothelial compartment, the macrophages ingest the lipid, becoming foam cells

9 4: Accumulation of foam cells make up the early atherosclerotic lesion: the fatty streak

10 5: Plaque progression. Over 20 to 40 years, the plaque continues To grow, until

11 Coronary Artery Plaque/Rupture

12 12 Lessons Learned from Intravascular Imaging

13 Coronary Angiogram: Provides a great silhouette of the lumen But the action is in the vascular wall 13

14 14 Coronary Imaging Intravascular Ultrasound (IVUS)

15 Unstable/Vulnerable Plaque vs Stable Plaque Thickness of fibrous cap covering plaque Lipids, WBC s and enzymes within plaque Connective tissue within plaque Risk of rupture Associated clinical sydromes Stable plaque Thick Small amt Large amt Low Stable exertional angina Unstable/ vulnerable plaque Thin Large amt Small amt High Acute coronary syndromes, sudden death

16 16 Unstable vs Stable Plaque

17 Acute Coronary Syndromes Biological/Clinical Correlation Changing the vulnerable plaque to a quiescent, stable plaque is major focus of treatment of CAD patients Statins (lipid lowering drugs) BP control Inhibition of renin angiotensin system Tobacco avoidance

18 High Dose Statin Therapy Induces Regression in Plaque Size and Change in Plaque Biology Baseline After 24 months statin tx

19 Plaque STABILIZATION (Not Regression/Shrinkage) is the major benefit of aggressive lipid lowering Lower levels of circulating LDL cholesterol Less oxidized LDL infiltrating the arterial wall Fewer macrophages infiltrating the arterial wall Fewer enzymes to degrade the cap of the plaque Plaque less likely to rupture Lower risk of myocardial infarction

20 Acute Coronary Syndromes Pathogenesis of Coronary Thrombosis RBC s WBC s Fibrin strands Platelets

21 Coronary Thrombosis: Clot begets Clot Ruptured plaque promotes thrombin formation and recruits platelets to site Thrombin stimulates platelet activation Activated platelets accelerate thrombin formation

22 Coronary Thrombosis: Clot begets Clot Antiplatelet drugs Antithrombin drugsruptured plaque promotes thrombin formation and recruits platelets to site Antiplatelet drugs Antithrombin drugs Thrombin stimulates platelet activation Activated platelets accelerate thrombin formation Antiplatelet drugs Antithrombin drugs

23 The Primacy of the Platelet in Acute Coronary Syndromes Inferior STEMI 100% native RCA Acute thrombosis of LAD stent

24 Keys to breaking the Vicious Cycle of Coronary Thrombosis Antiplatelet drugs Aspirin Clopidogrel Prasugrel IIb/IIIa glycoprotein receptor antagonists Antithrombin drugs Unfractionated Heparin Low molecular weight heparins Bivalirudin Argatroban

25 Acute Coronary Syndromes (USA/NSTEMI/STEMI): Treatment Principles Restore normal coronary blood flow as soon as possible Address coronary thrombosis, interrupt cycle Optimize myocardial oxygen demand-supply ratio (Decrease HR, BP, wall tension) Interrupt sympathetic nervous system/catecholamine stimulation of heart In STEMI patients and high risk, unstable USA/NSTEMI patients, immediate cardiac cath/reperfusion

26 Acute Coronary Syndromes Treatment:USA/NSTEMI/STEMI Statins Reduce inflammation inside culprit plaques and other plaques throughout the body. Beta blocker Decrease HR, BP, myocardial oxygen demand Nitrates Decreases myocardial oxygen demand by decreasing preload, wall tension Improves coronary perfusion directly by dilating coronary arteries

27 Acute Coronary Syndromes Treatment:USA/NSTEMI/STEMI Clopidogrel/Prasugrel/Ticlopidine/Ticagrelor Inhibits ADP-induced platelet activation Aspirin Inhibits thromboxane A2-mediated platelet activation IIb/IIIa platelet receptor antagonists Inhibits final common pathway of platelet aggregation Reduces composite of death and MI in ACS pts Unfractionated Heparin or Low molecular weight Heparin Inhibits thrombin

28 Acute Coronary Syndromes Treatment: USA/NSTEMI/STEMI When or whether to perform cardiac catheterization with coronary angiography? In STEMIs---emergently, unless there is a major contraindication If pain persists despite maximal medical treatment, urgent cardiac cath with revascularization (coronary stent placement or CABG) is indicated If pain resolves with medical treatment, but patient with high risk markers, cardiac cath and revascularization before hospital discharge (High TIMI Risk Score) Very low risk patients without recurrent symptoms can be managed conservatively, with cardiac catheterization performed only for recurrent symptoms

29 Cardiac Catheterization/Coronary Angiography

30 Acute Coronary Syndromes: Treatment:STEMI Thrombus Complex plaque Lumen

31 Acute Coronary Syndromes: Treatment:STEMI Immediate reperfusion therapy (coronary balloon angioplasty/stent placement or fibrinolytic drug therapy ) Restore normal coronary blood flow ASAP ( Time is muscle ) Beta blockers, nitrates, antiplatelets, anti-thrombins, and statin drugs are initiated immediately

32 Acute Coronary Syndromes STEMI Fibrinolytic therapy Plasmin: enzyme that digests fibrin strands of a clot, effectively lysing the clot Plasminogen: Pro-enzyme of plasmin. Needs to be cleaved to plasmin Plasminogen activators: enzymes that cleave plasminogen to plasmin: Streptokinase (rarely used in US) Tissue type plasminogen activator (tpa) Tnk-tPA (modified tpa with longer half-life) rpa (modified tpa with longer half-life) Others (urokinase, APSAC, vampire bat saliva, etc.)

33 Fibrinolytic therapy: (Plasminogen activators that cleave plasminogen to plasmin) Plasmin: digests fibrin strands, rendering clot unstable Antiplatelet agents: prevent further platelet aggregation Antithrombin agents: prevent production of more fibrin strands Clot

34 STEMI: Percutaneous Coronary Intervention (PCI) Catheter introduced into femoral, Brachial, or radial artery, advanced up to heart X ray dye injected into coronary arteries to identify blocked artery Blocked artery opened with tiny balloon and stent

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36 Immediate Reperfusion in STEMI: Fibrinolytic Therapy vs PCI Fibrinolytic drug tx Percutaneous intervention Improves survival in STEMI pts Improves survival in STEMI pts Works within 90 min of initiation of tx Works within <30 min of initiating cath Initial success in 65-75% of pts Initial success in >95% of pts 20-30% of pts reocclude artery <1% of pts reocclude artery Intracranial bleed in approx 1% Intracranial bleed risk <0.1% Artery often left with moderate or severe residual stenosis Available in all hospitals Artery usually left with 0% residual stenosis Available in <1/3 of hospitals

37 STEMI Treatment: Fibrinolytic Therapy vs Percutaneous Coronary Intervention (PCI) In multiple head-to-head studies, PCI (balloon angioplasty with stent placement) in STEMI pts proved superior to fibrinolytic drug therapy (better survival, better myocardial salvage, lower complication rates) Most hospitals do not have an interventional cath lab If pts present to hospitals without cath lab, they have better outcomes if they can be transported to a cath lab and have PCI within 90 minutes

38 Treatment of STEMI: Coronary Stenting vs Fibrinolytic therapy Bottom line: Stenting >>>fibrinolytic therapy>>>nothing

39 Acute Coronary Syndromes: Treatment:STEMI Whether treating the STEMI pt with fibrinolytic therapy or mechanical revascularization, patients who receive the treatment early (2-3 hrs from pain onset) have ½ the mortality of people who receive the treatment late (>6 hrs after pain onset) This is a major problem, with delays at several steps: Patient delays seeking medical help (denial, poor access, social issues) Delay in ER staff performing EKG Delay in EKG being presented to MD for interpretation Delay in drugs being mixed in pharmacy and administered to pt Delay in transporting pt from ER to cath lab or from one hospital to another Delay in cath lab staff coming in from home

40 Cases from The OSU Ross Heart Hospital

41 Inferior STEMI EKG 1615 after ROSC

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48 Sudden Cardiac Death While Exercising

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56 Inferior STEMI Artery Reperfused With Lytic Therapy

57 Inferior STEMI Artery Reperfused With Lytic Therapy

58 Inferior STEMI Artery Reperfused With Lytic Therapy

59 Anterior-Lateral MI with Cardiogenic Shock

60 Anterior-Lateral MI with Cardiogenic Shock

61 Anterior-Lateral MI with Cardiogenic Shock

62 Anterior-Lateral MI with Cardiogenic Shock

63 Unstable Angina

64 Unstable Angina

65 Unstable Angina

66 Anterior STEMI

67 Anterior STEMI Occluded prox-mid LAD

68 Anterior STEMI

69 Anterior STEMI

70 5 Minutes Later...

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72 72 Discharge after STEMI: What Rx?

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74 Acute Coronary Syndromes STEMI: The Aftermath Therapies to start before hospital discharge: ACE inhibitors (prevent post-mi cardiac enlargement or remodeling, and sudden death) Statins (decrease lipids and change vulnerable, ruptureprone plaques to stable plaques) Aldosterone receptor antagonists (improve survival in pts with severe LV dysfunction post-mi) (These are all in addition to ASA, P2Y12 inhibitor, betablocker)

75 Acute Coronary Syndromes: Summary Acute coronary syndromes range from unstable angina without infarction, to STEMI. Stable plaques are filled with connective tissue, are metabolically inactive, and cause stable exertional angina Unstable or vulnerable plaques are lipid-filled, tense, metabolically active, and prone to rupture, causing acute coronary syndromes A main focus of treating CAD pts is transforming vulnerable plaques to stable plaques. Statins are the drugs with the most evidence supporting this.

76 Acute Coronary Syndromes: Summary Coronary thrombosis is a hallmark of acute coronary syndromes Much of the therapy for ACS is directed at interrupting the vicious cycle of thrombosis (e.g., ASA, clopidogrel, heparin, IIb/IIIa blockers) In STEMI, emergent reperfusion can be life-saving, the sooner the better In STEMI patients, PCI (coronary stenting) results in greater myocardial salvage and better survival than fibrinolytic therapy, but only if it can be performed expeditiously. If no cath lab is available, do not delay giving fibrinolytic therapy, which is also a lifesaving therapy

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