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

Conflict of Interest No payment by industry No shares in industry

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

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

Anesthesiology 2009; 111(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

GUIDELINES

POISE. Lancet 2008; 371: Risk HR(95%CI)=0.83( ), p= # at Risk M P Metoprolol Placebo POISE Primary Outcomes

POISE. Lancet 2008; 371: Days Metoprolol Placebo HR(95%CI)=0.70( ), p= M P POISE Non-fatal MI Risk

POISE All Cause Mortality Risk Days Metoprolol Placebo HR(95%CI)=1.33( ), p= No. at Risk M P POISE. Lancet 2008; 371:

CVC by Sx urgency and treatment assignment Number at risk:

Mortality by surgical urgency and treatment assignment Number at risk:

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

PREDICTABLE PREOP?

POISE: Table 5

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 > (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 > (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) (0.373,0.869 )

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 (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) (0.262, )

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

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

MANAGEMENT OPTIONS

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

Pooled sensitivity: 94% (95% CI, 92%-96%) specificity: 96% (94%-97%) the AUC for ROC was 0.99 ( ) “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”

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 /aas12343

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.

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?

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

Systolic Heart Failure Circulation 2002; 105:

Diastolic Heart Failure Circulation 2002; 105:

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

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