Agenda. Perioperative Cardiac Risk Stratification circa Surgical Mortality: What is High Risk? Presenter Disclosure Information

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9:45 1:45 am Perioperative Evaluation and Management of the Cardiac Patient in Noncardiac Surgery SPEAKER Joshua A. Beckman, MD, MS Presenter Disclosure Information The following relationships exist related to this presentation: Joshua A. Beckman, MD, MS: Advisory Board for Bayer; Bristol-Myers Squibb; Merck & Co., Inc.; and Novartis Pharmaceuticals Corporation. Contracted Research for Bristol-Myers Squibb and Merck & Co., Inc. Ownership Interest in EMX and Jana Care Inc. Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Agenda Perioperative Evaluation and Management of the Cardiac Patient in Noncardiac Surgery Objectives pmicme Joshua A. Beckman, M.D., M.S. Vanderbilt University Risk of noncardiac surgery Risk stratification Patient-based Procedure-based Modifiers Follow up Perioperative Cardiac Risk Stratification circa 1977 Determination of factors that predict major events and death after major surgery in 11 patients over the age of 4 years 6 5 4 3 2 1 Severe Event (MI, APE, VT) Events (%) I <6 II 6-12 III 13-25 IV > 25 Goldman, L. NEJM 1977;297:845 Surgical : What is High Risk? Operation N Age (years) Emergent Status (%) 3-Day (%) AAA Repair 3767 69±7 6 4.7 Infrainguinal Vascular Bypass 12535 65±9 6 3.1 CEA 1173 67±8 2.5 1.2 Lobectomy / 489 65±9.6 5.5 Pneumonectomy Laparoscopic 862 58±37 2.5.5 Cholecystectomy Colectomy 1331 66±11 18.6 6.9 Total Hip Arthroplasty 8241 63±12.8 1. Khuri, SF. Ann Surg 1999;23(3):414

Methods for Assessing Risk Pre-Operatively Patient-based High-risk conditions Functional Capacity Surgery-based Vascular Surgery Emergency surgery Intervention-based Medications Revascularization High Risk (Unstable) Conditions: Fix These Pre-Op! Unstable coronary syndromes Unstable or severe angina* (CCS class III or IV) Recent MI (>7, <3 days) Decompensated HF NYHA functional class IV Worsening or new-onset HF Significant arrhythmias High-grade atrioventricular block (Mobitz II, Third-degree AV block) Mobitz II atrioventricular block Third-degree atrioventricular heart block Symptomatic ventricular arrhythmias Supraventricular arrhythmias (including AF) with HR > 1 Symptomatic bradycardia Newly recognized ventricular tachycardia Severe valvular disease Severe aortic stenosis (mean pressure gradient greater than 4 mm Hg, aortic valve area less than 1. cm2, or symptomatic) Symptomatic mitral stenosis ACC/AHA Periop Guidelines 27 Effect of Prior CABG on Cardiac Risk of Vascular Surgery: The CASS Registry The Trump Card: Functional Capacity Event Rate (%) 1 8 6 4 2 (n=314) 3. No CAD *** 8.5 * 2.8 CAD: Medical Rx Periop MI *** *.6 1.1 CAD: CABG Perioperative cardiac risk is increased in patients unable to exercise 4 METs* Functional capacity can be estimated in the office Energy expenditure for eating, dressing, walking around house, dishwashing ranges from 1-4 METs Climbing a flight of stairs, running a short distance, scrubbing floors, and golf ranges from 4-1 METs Swimming and singles tennis exceeds 1 METs * Metabolic equivalent Eagle et al. Circulation, 1997 A Rapid Functional Screen: Exercise Role of Noninvasive Testing Events Prior to D/C (%) 6 consecutive pts w/consultation for preoperative evaluation before major noncardiac procedures stratified by exercise tolerance 1 Cardiovascular Complications Exercise Tolerance 2 flights/4blocks < 2 flights/4blocks Reilly, D. Arch Int Med 1999;159(18): 2185 What is the amount of myocardium in jeopardy? Is there multivessel disease? What is the ischemic threshold, i.e. amount of stress required to produce ischemia? What is the ventricular function?

Prognostic Interpretation of ECG- Monitored Exercise Test High Risk Ischemia induced by low level exercise (<4 METs) Eating, dressing, walking around house, dishwashing Intermediate Risk Ischemia induced by moderate level exercise (4-6 METs) Climbing a flight of stairs, running a short distance, scrubbing floors, and golf Low Risk No ischemia or ischemia induced at high level exercise (>7 METs) Swimming and singles tennis Predictive Value of Preoperative Exercise Testing before Surgery Predictive Value Author n % Abn Positive Negative McCabe 81 314 36 81% 91% Cutler 81 13 39 16% 99% Arous 84 88 17 21% NR Gardine 85 86 48 11% 9% von Knorring 86 15 25 8% 99% Kopecky 86 114 57 13% 1% Leppo 87 6 28 25% 92% Hanson 88 74 57 5% 1% McPhail 88 1 7 24% 93% Urbinati 94 121 23 % 1% Graybum, PA. Ann Intern Med 23; 138:56 Predictive Value of Preoperative Vasodilator- Nuclear Testing before Surgery MI or Predictive Value Author n Positive Negative Eagle 2 8 16% 98% Cutler 116 1 2% 1% Younis 111 7 15% 1% Hendel 327 9 14% 99% Lette 355 8 17% 99% Brown 321 5 13% 99% Vanzetto 134 9 13% 98% Baron 457 5 4% 96% Bry 237 7 11% 1% Roghi 32 4 5% 98% Surgery-Specific Risk: High Risk* Major emergency surgery Vascular surgery including: aortic surgery, infra-inguinal bypass Prolonged surgery with large fluid shifts or blood loss * Reported risk of cardiac death or nonfatal MI >5% Graybum, PA. Ann Intern Med 23; 138:56 Assessment of Possible Risk- Reduction Interventions Medications Beta Adrenergic Blockers Statins Coronary Artery Revascularization CABG PCI Invasive Pressure Monitoring -Blockade and Perioperative Risk 112 patients undergoing vascular surgery with positive DBA stress test, randomized to bisoprolol or usual care Patients (%) 4 3 2 1 Standard Care P <.1 Bisoprolol 7 14 21 28 Days after surgery Poldermans, NEJM 1999: 1789

POISE Trial 8351 patients 45 years or older undergoing noncardiac surgery with a history of CAD, PAD, stroke, or CHF within 3 years undergoing major vascular surgery; or have 3 of 7 risk factors undergoing high-risk surgery. Patients randomized to receive either metoprolol CR or placebo started 2-4 hrs preop and continued for 3 days at 1 mg preop, 1 mg in the six-hour post-op, 2 mg 12 hours later, and 2 mg daily thereafter. Outcome Metoprolol (n=4174), (n=4177), ratio P-value Primary composite 243 (5.8) 29 (6.9).83.4 Nonfatal MI 151 (3.6) 215 (5.1).7.7 Total mortality 129 (3.1) 97 (2.3) 1.33.3 Stroke 41 (1.) 19 (.5) 2.17.5 Devereaux, PJ. Lancet 28; 371(9627)1829 POISE Trial Outcome Metoprolol (n=4174), (n=4177), ratio P-value Revascularization 11 (.3) 27 (.6).41.1 Atrial fibrillation 91 (2.2) 12 (2.9).76.4 Significant hypotension 626 (15.) 44 (9.7) 1.55 <.1 Significant bradycardia 274 (6.6) 11 (2.4) 2.71 <.1 Devereaux, PJ. Lancet 28; 371(9627)1829. Statins Improve Survival After Vascular Surgery 1 pts randomized 2 mg atorvastatin or placebo for 45 days. Vascular surgery ~ 3 days after randomization. F/U 6 months Event free survival (%) 1 8 6 4 2 Primary Endpoint CV death + NFMI+ Ischemic stroke+ Unstable Angina Atorvastatin 3 6 9 12 15 18 Days after Surgery The Catheterization Questions to Ask Yourself Does this patient have symptomatic coronary disease that will have a mortality benefit from revascularization now? Am I willing to send the patient to CABG? Am I doing this just to know the anatomy? Durazzo, AES. JVS 24:39(5):975 The Effect of Percutaneous Revascularization Above Optimal Medical Therapy: COURAGE 2287 Pts w/myocardial ischemia and CAD randomized to PCI with optimal medical therapy (PCI group) and 1138 to medical therapy alone. Survival Free of /MI 1..9.8.7.6.5 Medical therapy PCI + Medical therapy 1 2 3 4 5 6 7 Years Boden, W. NEJM 27; 356:153 Age Pre-Operative Stenting May Cause Catastrophic Outcomes Ticlid withheld ASA withheld Surgery Major Bleeding 82 Yes Yes Femoral No 11 embolectomy 62 No No CEA Yes 7 72 No Yes MVR Yes 3 68 Yes Yes CEA Yes 8 67 Yes Yes TAA repair No No 67 No Yes TAA repair Yes 8 72 Yes Yes Colectomy No 2 62 Yes Yes Lung TXP Yes 11 74 Yes Yes TAA repair Yes 9 Kaluza, G. JACC 2;35:1288

Coronary Revascularization Does Not Improve Immediate or Long-Term Outcomes 51 VA pts, aged 66 years, with stable CAD, scheduled for elective AAA repair (33%) or infrainguinal bypass (67%), randomized to Revasc (PCI 59%, CABG 41%) or conservative management. 25 2 15 1 CAD Severity in 148 patients who had coronary angiography in CARP Extent of CAD No. of Patients 2.5 Year Survival Ratio 1 Vessel 41.6% 84% 1 pvalue 2 Vessels 19.5% 79% 1.64.4 3 Vessels 12.4% 75% 1.87.1 5 Post-Op MI 3 Day Revascularization 2.7 Year Conservative Mgmt McFalls, E. CARP Trial;AHA 24 Left Main CAD Previous CABG 4.6% 74% 1.64.12 21.5% 78% 1.58.9 Garcia, S. Am J Cardiol 28;12:89 813 Swan-Ganz Catheters in Major Surgery 1994 patients >6 YO (ASA) class III or IV risk scheduled for urgent or elective major abdominal, thoracic, vascular, or hip-fracture surgery Proportion Surviving 1..8.6.4.2 Standard Care Pulmonary artery catheter. 2 4 6 8 1 12 Months Surveillance for Perioperative Myocardial Infarction ECGs All intermediate and high-risk patients should get a post-op ECG. As needed for signs or symptoms of ischemia Troponin/CK In patients with signs or symptoms of ischemia Do not do screening biomarkers Sandham, JD. NEJM 23; 348(1):5-14 Peak TNT (ng/ml) Postoperative TNT Levels and 3-Day In Noncardiac Surgery A prospective, international cohort study that enrolled 15133 noncardiac patients (aged 45 Years or older) from 27 to January 11, 211. TnT levels were measured 6 to 12 hours after surgery and on days 1, 2, and 3. Vascular (n = 127) Number died/ Number group Adjusted HR Nonvascular (n = 155) Number died/ Number group <.1 56/13376 1 78/13376 1.2 7/494 1.65 13/494 3.25.3 51/1121 4.81 53/1121 5.6.29.3 13/142 1.1 11/142 9.2 Adjusted HR Vascular death was defined as deaths following MI, cardiac arrest, stroke, PCI or CABG, pulmonary embolus, hemorrhage, or deaths due to an unknown cause. Devereaux, PJ. JAMA. 212;37(21):2295-234 Take Home Messages Unstable syndromes require management prior to surgery. Look for: Unstable angina Signs of heart failure Stenotic valve lesions Ventricular arrhythmias Functional tolerance is the best single predictor of outcome. Be very specific in your history (one step at a time, regular or slow pace, etc.) Every patient should get beta blockers & statins unless contraindicated. PCI/CABG only if patient needs it independent of surgery. Think twice because of stent data and delays.