1. Translating evidence into practice: cardiac patients for non-cardiac surgery H Yang Professor & Chair Department of Anesthesia

2. Conflict of Interest No payment by industry No shares in industry

3. Objectives Understand the statistics on perioperative myocardial infarctions (POMI) Review status of prophylaxis against POMI Discuss pre-op risk stratification Discuss management options

4. Lindenauer et al. NEJM 2005; 353:349 - 61 Perioperative Mortality 541297 (did not receive  -blockers) 10771 (1.98%) RCRI Factors ≤ 1RCRI Factors ≥ 2 8443 (1.73%) 2328 (4.23%) 78% of all mortality 22 % of all mortality

5. Anesthesiology 2009; 111(4): 690-4 Effect of β-blockers in Postop Hip & Knee Replacements 23 (5.0–106)14 (0.3%)2 (2.6%)Class IV 38 (19–75)63 (1.2%)15 (19.5%)Class III 10 (6.1–17)502 (9.9%)32 (41.6%)Class II 4502 (88.6%)28 (36.4%)Class I ORNo PMI (n=5081)PMI (n=77) Anesthesiology 2009; 111:717–24

6. GUIDELINES

7. POISE. Lancet 2008; 371:1839-47 Risk 0.0 0.02 0.04 0.06 0.08 0102030 HR(95%CI)=0.83(0.70-0.99), p=0.035 4177391538733853 4174395939093879 # at Risk M P Metoprolol Placebo POISE Primary Outcomes

8. POISE. Lancet 2008; 371:1839-47 0.0 0.02 0.04 0.06 0.08 0102030 Days Metoprolol Placebo HR(95%CI)=0.70(0.56-0.86), p=0.0007 4177392338823859 4174397639223889 M P POISE Non-fatal MI Risk

9. POISE All Cause Mortality Risk 0.0 0.01 0.02 0.03 0102030 Days Metoprolol Placebo HR(95%CI)=1.33(1.02-1.74), p=0.032 4177411640914069 4174411340664038 No. at Risk M P POISE. Lancet 2008; 371:1839-47

10. CVC by Sx urgency and treatment assignment Number at risk: 3736 3571 35303515 3506 3500 3494 438 401 397 393 391 390 389 3729 3606 3572 3558 3550 3539 3533 440 407 401 398 395 393 392

11. Mortality by surgical urgency and treatment assignment Number at risk: 3736 3719 3698 3687 3678 3672 3666 438 428 420 417 413 407 406 3729 3709 3692 3676 3660 3647 3639 440 426 414 407 400 396 394

12. Large Database Propensity Matched Studies LindenauerLondon Total matched 335,92275610 RCRI 0 1.43 (1.29 – 1.58) (n=141,916) No effect (n=24,500) RCRI 1 1.13 (0.99 – 1.30) (n= 137,353) No effect (n=32,114) RCRI 2 0.90 (0.75 – 1.08) (n=53,238) 0.63 (0.50 – 080) (n=13,590) RCRI 3 0.71 (0.56 – 0.91) (n=12,260) 0.54 (0.39 – 073) (n=4,180) RCRI ≥ 4 0.57 (0.42 – 0.76) (n=1065) 0.40 (0.25 – 0.73) (n=1226) N Engl J Med 2005;353:349-61 JAMA, 2013; 309(16):1704 - 13

13. PREDICTABLE PREOP?

14. POISE: Table 5

15. Population Attributable Risk: Pre-op Variable Adjusted OR (95%CI) Frequency of at risk Factor n(%) PAR (95% CI) Statin 1.520(1.087,2.126)5674(67.94%)0.274(0.064,0.462) Age > 70 1.990(1.475,2.684) 4311(51.67%)0.361(0.201,0.501) Emergent Sx 3.302(2.441,4.466) 878(10.51%)0.242(0.128,0.349) Creat > 175 3.312(2.246,4.885) 401(4.80%)0.114(0.05,0.177) CHF 1.674(1.103,2.541) 499(5.98%)0.052(-0.006,0.11) LMWH 1.507(1.004,2.261)556(6.66%)0.049(-.016,0.113) Full PAR (95% CI) 0.696 (0.373,0.869 )

16. Population Attributable Risk: Post-op Variable Adjusted OR (95%CI) Frequency of at risk Factor n(%) Par(95% CI) hypotension 4.684(3.451,6.358) 1029(12.32%)0.424(0.213,0.597) MI wo sympt 3.338(2.156,5.169) 279(3.34%)0.143(0.023,0.26) Bleed 1.750(1.207,2.538) 553(6.62%)0.12(-0.014,0.249) Stroke 14.762(7.914,27.535) 60(0.72%)0.156(0.022,0.285) Bradycardia 2.085(1.368,3.178) 351(4.20%)0.089(0.006, 0.17) MI w sympt 3.023(1.659,5.509)164(1.96%)0.043(0.007,0.079) Full PAR (95% CI) 0.592 (0.262, 0.798 )

17. Non-Obstructive ? Supply & Demand No Culprit Lesions ACS MI Type 1 Plaque Rupture Type 2 Supply & Demand Unstable Plaque Stable CAD Hemodynamics ( ↓BP, ↑HR ) Coronary Vasoconstriction ↑ Sympathetic Tone (pain) ↓ volume ↑ inflammation (statins) ↑ coagulability (ASA, clopidogrel) Plaque RupturePlaque Erosion Type 1 ACS MIType 2 ACS MI ↑ MVO2 ↑ HR ↑LVEDP ↑afterload (BP) ↑contractility ↓Supply ↓ Hb ↓ O2 ↑ LVEDP ↓ BPd ↑ HR Pre-op Predictable Stable CAD ↑ inflammation (statins) ↑ coagulability (ASA, clopidogrel) Pre-op Non-predictable Unstable Plaque Hemodynamics ( ↓BP, ↑HR ) Coronary Vasoconstriction ↑ Sympathetic Tone (pain) ↓ volume ↑ MVO2 ↑ HR ↑LVEDP ↑afterload (BP) ↑contractility ↓Supply ↓ Hb ↓ O2 ↑ LVEDP ↓ BPd ↑ HR No Culprit Lesions

18. Pre-op Predictable Stable CAD ↑ inflammation (statins) ↑ coagulability (ASA, clopidogrel) Pre-op Non-predictable Unstable Plaque Hemodynamics ( ↓BP, ↑HR ) Coronary Vasoconstriction ↑ Sympathetic Tone (pain) ↓ volume ↑ MVO2 ↑ HR ↑LVEDP ↑afterload (BP) ↑contractility ↓Supply ↓ Hb ↓ O2 ↑ LVEDP ↓ BPd ↑ HR No Culprit Lesions

19. MANAGEMENT OPTIONS

20. What next? Beta-blockers for high risk elective patients Still uncertain about – Emergency cases – Previous CVA patients – Low risk patients Nothing else has had an impact New Paradigms – Pre-op echo in emergency cases – Diastolic Dysfunction – Stem cells – Postop monitoring

22. Pooled sensitivity: 94% (95% CI, 92%-96%) specificity: 96% (94%-97%) the AUC for ROC was 0.99 (0.98-0.9) “General practitioners and Emergency Medicine physicians should be encouraged to learn LUS since it appears to be an established diagnostic tool in the hands of experienced physicians”

23. Routine Preop FATE in urgent Sx To quantify unexpected cardiopulmonary pathology by FATE in unselected patients undergoing urgent surgery & to evaluate impact of unexpected pathology on choice of anesthesia techniques or supportive actions Acta Anaesthesiologica Scandinvica 2014; May 28. DOI 10.1111/aas12343

24. Assessment Criteria 1.Pericardial effusion ≥ 10 mm present? 2.Left ventricle end diastolic diameter ≥ 6.2 cm, indicating left ventricle dilation? 3.Mid right ventricle end diastolic diameter ≥ 42 mm or tricuspid annular plane systolic excursion ≤ 16 mm, indicating right ventricle dilation or systolic dysfunction? 4.Left ventricle septal or posterior wall thickness ≥ 13 mm? In case hypertrophy was present, we assessed whether left atrium diameter was > 50 mm, indicating diastolic dysfunction.

25. Assessment Criteria II 5.Ejection fraction ≤ 40% by eyeballing, indicating left ventricle systolic dysfunction? 6.Visible aortic valve sclerosis? In case sclerosis was present, supervisors assessed whether maximum jet velocity over the aortic valve by Continuous Wave Doppler was ≥ 3 m/s, indicating aortic stenosis. 7.Other obvious pathological findings, processes or excrescences present? 8.Any pleural effusion present?

28. Diastolic Dysfunction Random sampling of general population – Diastolic Dysfunction in 27.3% – Echo diagnosis CPP = BP d - LVEDP

29. Systolic Heart Failure Circulation 2002; 105:1387-93

30. Diastolic Heart Failure Circulation 2002; 105:1387-93

31. Molecular Phenotype of MSC Treated Septic Mice dos Santos et al, AJP 2012

32. Summary Pathophysiology – At least 25% of PMI is Type 2 – “non-obstructive” category exists – Hemodynamic → Type 1 & Type 2 Pre-op risk stratification is limited by unpredictable intra- & post-op events Judicious use of beta-blockers Need for new paradigms