1. Todd C. Villines, MD Cardiology Service Cardiology Board Review Part I April 2008 Walter Reed Army Medical Center

4. Acute Coronary Syndromes Revascularization

5. Hospitalizations in the U.S. Due to Acute Coronary Syndromes (ACS) Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI † STEMI 1.24 million Admissions per year .33 million Admissions per year Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69-171. *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA.

6. ACS - Thrombolytics Greatest benefit of thrombolytics in first 1-2 hours from symptom onset! (Golden Hour) ABSOLUTE Contraindications

7. Thrombolytics Relative Contraindications

8. ACS Things you must know… 1. 2. 3. 4. Rescue Angioplasty If no reperfusion in 60-90 mins. (20-40% will not reperfuse) If hemodynamically stable: no treatment! (CK washout ) Accelerated Idioventricular Rhythm (AIVR)

10. Primary PCI

11. Primary PCI STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within 90 min of first medical contact as a systems goal. STEMI patients presenting to a hospital without PCI capability, and who cannot be transferred to a PCI center and undergo PCI within 90 min of first medical contact, should be treated with fibrinolytic therapy within 30 min of hospital presentation as a systems goal, unless fibrinolytic therapy is contraindicated. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B

12. Facilitated PCI

13. Meta-analysis: Facilitated PCI vs Primary PCI 1.03 (0.15-7.13) 3.07 (0.18-52.0) 1.43 (1.01-2.02) 1.03 (0.49-2.17) Mortality Reinfarction Major Bleeding Fac. PCI Better PPCI Better Fac. PCI Better PPCI Better Fac. PCI Better PPCI Better Keeley E, et al. Lancet 2006;367:579. 0.1 1 10 0.1 1 10 0.1 1 10 1.38 (1.01-1.87) 1.71 (1.16 - 2.51) 1.51 (1.10 - 2.08 ) 1.40 (0.49-3.98) 1.81 (1.19-2.77) Lytic alone N=2953 All (N=4500) Lytic +IIb/IIIa N=399 IIb/IIIa alone N=1148

14. A planned reperfusion strategy using full-dose fibrinolytic therapy followed by immediate PCI is not recommended and may be harmful. Facilitated PCI using regimens other than full-dose fibrinolytic therapy might be considered as a reperfusion strategy when all of the following are present: a. Patients are at high risk, b. PCI is not immediately available within 90 minutes, and c. Bleeding risk is low (younger age, absence of poorly controlled hypertension, normal body weight). Facilitated PCI I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B

15. Rescue and Late PCI

16. Meta-analysis: Rescue PCI vs Conservative Tx Wijeysundera HC, et al. J Am Coll Cardiol. 2007;49:422-430. In 3 trials, enrolling 700 patients that reported the composite end point of all-cause mortality, reinfarction, and HF, rescue PCI was associated with a significant RR reduction of 28% (RR 0.72; 95% CI, 0.59-0.88; P =.001) P RR (95% CI) Conservative Treatment Rescue PCI Outcome <.001 4.58 (2.46–8.55) 3.6 (307) 16.6 (313) Minor bleeding, % (n) .04 4.98 (1.10–22.48) 0.7 (295) 3.4 (297) Stroke, % (n) .04 0.58 (0.35–0.97) 10.7 (354) 6.1 (346) Reinfarction, % (n) .05 0.73 (0.54–1.00) 17.8 (427) 12.7 (424) HF, % (n) .09 0.69 (0.46–1.05) 10.4 (457) 7.3 (454) Mortality, % (n)

18. Rescue PCI A strategy of coronary angiography with intent to perform PCI (or emergency CABG) is reasonable in patients ≥ 75 years who have received fibrinolytic therapy, and are in cardiogenic shock, provided they are suitable candidates for revascularization.

23. Analgesia Patients routinely taking nonsteroidal anti-inflammatory drugs (NSAIDs) (except for aspirin), both non-selective as well as COX-2 selective agents, prior to STEMI should have those agents discontinued at the time of presentation with STEMI because of the increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture associated with their use.

24. Analgesia NSAIDs (except for aspirin), both nonselective as well as COX-2 selective agents, should not be administered during hospitalization for STEMI because of the increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture associated with their use. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

25. Beta-Blockers

27. Effects of Metoprolol Lancet . 2005;366:1622. Death 13% P=0.0006 ReMI 22% P=0.0002 VF 15% P=0.002 Totality of Evidence (N = 52,411) COMMIT (N = 45,852) Increased early risk of shock Risk factors for cardiogenic shock :heart failure, age > 70 , systolic blood pressure < 120, sinus tachycardia > 110 or heart rate < 60, increased time since onset of STEMI symptoms

28. Oral beta-blocker therapy should be initiated in the first 24 hours for patients who do not have any of the following: 1) signs of heart failure, 2) evidence of a low output state, 3) increased risk* for cardiogenic shock, or 4) other relative contraindications to beta blockade (PR interval > 0.24 sec, 2 nd - or 3 rd -degree heart block, active asthma, or reactive airway disease). It is reasonable to administer an IV beta blocker at the time of presentation to STEMI patients who are hypertensive and who do not have any of the following: 1) signs of heart failure, 2) evidence of a low output state, 3) increased risk* for cardiogenic shock, or 4) other relative contraindications to beta blockade (PR interval > 0.24 sec, 2 nd - or 3 rd -degree heart block, active asthma, or reactive airway disease). Beta-Blockers I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B

29. IV beta blockers should not be administered to STEMI patients who have any of the following: 1) signs of heart failure, 2) evidence of a low output state, 3) increased risk* for cardiogenic shock, or 4) other relative contraindications to beta blockade (PR interval > 0.24 sec, 2 nd - or 3 rd -degree heart block, active asthma, or reactive airway disease). Beta-Blockers I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A

30. Anticoagulants Patients undergoing reperfusion with fibrinolytics should receive anticoagulant therapy for a minimum of 48 hours (Level of Evidence: C) and preferably for the duration of the index hospitalization, up to 8 days (regimens other than unfractionated heparin [UFH] are recommended if anticoagulant therapy is given for more than 48 hours because of the risk of heparin-induced thrombocytopenia with prolonged UFH treatment). (Level of Evidence: A) Anticoagulant regimens with established efficacy include: ♥ UFH (LOE: C) ♥ Enoxaparin (LOE:A) ♥ Fondaparinux (LOE:B) I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A

31. Anticoagulants For patients undergoing PCI after having received an anticoagulant regimen, the following dosing recommendations should be followed: a. For prior treatment with UFH: administer additional boluses of UFH as needed to support the procedure taking into account whether GP IIb/IIIa receptor antagonists have been administered. (Level of Evidence: C) Bivalirudin may also be used in patients treated previously with UFH. (Level of Evidence: C) Recommendation continues on the next slide. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C

32. Anticoagulants b. For prior treatment with enoxaparin: if the last SC dose was administered within the prior 8 hours, no additional enoxaparin should be given; if the last SC dose was administered at least 8 to 12 hours earlier, an IV dose of 0.3 mg/kg of enoxaparin should be given. c. For prior treatment with fondaparinux: administer additional intravenous treatment with an anticoagulant possessing anti-IIa activity taking into account whether GP IIb/IIIa receptor antagonists have been administered. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B

33. Anticoagulants Because of the risk of catheter thrombosis, fondaparinux should not be used as the sole anticoagulant to support PCI. An additional anticoagulant with anti-IIa activity should be administered. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C

34. ExTRACT-TIMI 25: Primary End Point (ITT) Death or Nonfatal MI Primary End Point (%) Enoxaparin UFH Relative Risk 0.83 (95% CI, 0.77 to 0.90) P <.001 Days after Randomization 9.9% 12.0% Lost to follow-up = 3 17% RRR Adapted with permission from Antman EM, et al. N Engl J Med . 2006;354:1477-1488.

35. CLARITY-TIMI 28 Primary Endpoint: Occluded Artery (or D/MI thru Angio/HD) Placebo Clopidogrel LD 300 mg MD 75 mg P=0.00000036 Odds Ratio 0.64 (95% CI 0.53-0.76) Clopidogrel better Placebo better n=1752 n=1739 Sabatine N Eng J Med 2005;352:1179. STEMI, Age 18-75 15.0 21.7 0 5 10 15 20 25 Occluded Artery or Death/MI (%) 1.0 0.4 0.6 0.8 1.2 1.6 36% Odds Reduction

36. COMMIT: Effect of CLOPIDOGREL on Death In Hospital Dead (%) Days Since Randomization (up to 28 days) Placebo + ASA: 1,846 deaths (8.1%) Clopidogrel + ASA: 1,728 deaths (7.5%) 0.6% ARD 7% RRR P = 0.03 N = 45,852 No Age limit ; 26% > 70 y Lytic Rx 50% No LD given Chen ZM, et al. Lancet . 2005;366:1607.

37. Clopidogrel 75 mg per day orally should be added to aspirin in patients with STEMI regardless of whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion therapy. Treatment with clopidogrel should continue for at least 14 days. Thienopyridines I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B

38. In patients < 75 years who receive fibrinolytic therapy or who do not receive reperfusion therapy, it is reasonable to administer an oral clopidogrel loading dose of 300 mg. (No data are available to guide decision making regarding an oral loading dose in patients ≥ 75 years of age.) Long-term maintenance therapy (e.g., 1 year) with clopidogrel (75 mg per day orally) can be useful in STEMI patients regardless of whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion therapy. Thienopyridines I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C

39. It is reasonable for patients with STEMI who do not undergo reperfusion therapy to be treated with anticoagulant therapy (non-UFH regimen) for the duration of the index hospitalization, up to 8 days. Convenient strategies that can be used include those with LMWH (Level of Evidence: C) or fondaparinux (Level of Evidence: B) using the same dosing regimens as for patients who receive fibrinolytic therapy. Anticoagulants I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B

40. Coronary arteriography may be considered as part of an invasive strategy for risk assessment after fibrinolytic therapy (Level of Evidence: B) or for patients not undergoing primary reperfusion. (Level of Evidence: C) Invasive Evaluation I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C

45. Goals Class I Recommendations For all post-PCI STEMI stented patients without aspirin resistance, allergy, or increased risk of bleeding, aspirin 162 to 325 mg daily should be given for at least 1 month after bare-metal stent implantation, 3 months after sirolimus-eluting stent implantation, and 6 months after paclitaxel-eluting stent implantation, after which long-term aspirin use should be continued indefinitely at a dose of 75 to 162 mg daily. Antiplatelet agents/ anticoagulants: Aspirin Secondary Prevention and Long Term Management CHANGED TEXT

46. Goals Recommendations In patients where the physician is concerned about the risk of bleeding lower-dose 75 to 162 mg of aspirin is reasonable during the initial period after stent implantation. (Class IIa; LOE: C) Antiplatelet agents/ anticoagulants: Aspirin Secondary Prevention and Long Term Management NEW REC

47. Goals Class I Recommendations For all post-PCI patients who receive a drug-eluting stent (DES), clopidogrel 75 mg daily should be given for at least 12 months if patients are not at high risk of bleeding. For post-PCI patients receiving a bare metal stent (BMS), clopidogrel should be given for a minimum of 1 month and ideally up to 12 months (unless the patient is at increased risk of bleeding; then it should be given for a minimum of 2 weeks). Antiplatelet agents/ anticoagulants: Clopidogrel Secondary Prevention and Long Term Management CHANGED TEXT

48. Goals Recommendations For all STEMI patients not undergoing stenting (medical therapy alone or PTCA without stenting), treatment with clopidogrel should continue for at least 14 d. (Class I; LOE: B) Long-term maintenance therapy (e.g., 1 year) with clopidogrel (75 mg per day orally) is reasonable in STEMI patients regardless of whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion therapy. (Class IIa; LOE: C) Antiplatelet agents/ anticoagulants: Clopidogrel Secondary Prevention and Long Term Management NEW RECS

49. Goals Class I Recommendations Managing warfarin to INR = 2.0 to 3.0 for paroxysmal or chronic atrial fibrillation or flutter is recommended, and in post-STEMI patients when clinically indicated (e.g., atrial fibrillation, left ventricular thrombus). Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with increased risk of bleeding and should be monitored closely. In patients requiring warfarin, clopidogrel, and aspirin therapy, an INR of 2 to 2.5 is recommended with low dose aspirin (75 to 81 mg) and a 75 mg dose of clopidogrel. Antiplatelet agents/ anticoagulants: Warfarin Secondary Prevention and Long Term Management NEW REC NEW REC CHANGED TEXT

51. Goals Class I Recommendations ACE inhibitors should be started and continued indefinitely in all patients recovering from STEMI with LVEF ≤ 40% and for those with hypertension, diabetes, or chronic kidney disease, unless contraindicated. ACE inhibitors should be started and continued indefinitely in patients recovering from STEMI who are not lower risk (lower risk defined as those with normal LVEF in whom cardiovascular risk factors are well controlled and revascularization has been performed), unless contraindicated. Among lower risk patients recovering from STEMI (i.e., those with normal LVEF in whom cardiovascular risk factors are well controlled and revascularization has been performed) use of ACE inhibitors is reasonable. (Class IIa; LOE: B) Renin-Angiotensin-Aldosterone System Blockers: ACE Inhibitors Secondary Prevention and Long Term Management NEW REC CHANGED TEXT NEW REC

52. Goals Class I Recommendations Use of ARBs is recommended in patients who are intolerant of ACE inhibitors and have HF or have had a STEMI with LVEF ≤ 40%. It is beneficial to use ARB therapy in other patients who are ACE-inhibitor intolerant and have hypertension. Considering use in combination with ACE inhibitors in systolic dysfunction HF may be reasonable. Renin-Angiotensin-Aldosterone System Blockers: ARBs Secondary Prevention and Long Term Management NEW REC NEW REC CHANGED TEXT

53. Goals Class I Recommendations Use of aldosterone blockade in post-STEMI patients without significant renal dysfunction or hyperkalemia is recommended in patients who are already receiving therapeutic doses of an ACE inhibitor and beta blocker, have an LVEF of ≤ 40% and have either diabetes or HF. Renin-Angiotensin-Aldosterone System Blockers: Aldosterone Blockade Secondary Prevention and Long Term Management CHANGED TEXT

54. Goals Class I Recommendations It is beneficial to start and continue beta- blocker therapy indefinitely in all patients who have had MI, acute coronary syndrome, or left ventricular dysfunction with or without HF symptoms, unless contraindicated. Beta- Blockers Secondary Prevention and Long Term Management CHANGED TEXT

63. MI: Initial Medical Therapy *Warfarin x 3-6 months: LV thrombus, large anterior MI with akinetic anterior wall. -Don’t give warfarin to a patient simply with a depressed EF without Afib or embolism or thrombus (controversial) *

82. Endocarditis Prophylaxis No Post-treatment 20 mg/kg IM or IV 600 mg IM or IV Clindamycin OR 50 mg/kg IM or IV 1 g IM or IV Cefazolin or ceftriaxone Allergic to penicillins or ampicillin and unable to take oral medication 15 mg/kg 500 mg Azithromycin or clarithromycin OR 20 mg/kg 600 mg Clindamycin OR 50 mg/kg 2 g Cephalexin* Allergic to penicillins or ampicillin - oral 50 mg/kg IM or IV 1 g IM or IV Cefazolin or ceftriaxone OR 50 mg/kg IM or IV 2 g IM or IV Ampicillin Unable to take oral medication 50 mg/kg 2 g Amoxicillin Oral Children Adults Regimen: single dose 30 to 60 min before procedure Agent Situation

100. Congenital Heart Disease

108. Todd C. Villines, MD Cardiology Service Cardiology Board Review Part II 2008 Walter Reed Army Medical Center

122. Atrial Fibrillation

138. Chest Pain suggestive of Pericarditis ECG Diagnostic ? Age < 40 & no other suspected systemic illness or traumatic ANY: JVD, Pulsus Paradoxus, +Cardiac Enzymes, Poor Pain Control in ER, No social support Admit / Reconsider If YES to ANY = Admit + Echo Suspect Pericarditis ? YES ECHO NO Large or Moderate Effusion Small Effusion -NSAIDS & F/U NO One Approach (MKSAP) Who to Admit ? Admit: - suspect serious underlying cause (e.g. - uremic) or on immunosuppressive Consider: 1. MI 2. Aortic Dissection 3. PE 4. Pneumothorax 5. Esophageal Rupture 6. Pancreatitis

151. Pre-Operative Evaluation A Must Know! Risk Stratify the Patient Risk Stratify the Surgery