CCS Perioperative Guidelines When to order a BNP and What to do with a Positive Troponin

Canadian Society of Internal Medicine Annual Meeting 2017 Toronto, ON CCS Perioperative Guidelines When to order a BNP and What to do with a Positive Troponin Dr. Vikas Tandon Associate Professor, Cardiology McMaster University November 1, 2017

CSIM Annual Meeting 2017 Conflict Disclosures I have the following conflicts to declare: Company/Organization Advisory Board or equivalent X X Details Speakers bureau member X X Payment from a commercial organization. (including gifts or other consideration or in kind compensation) X X Grant(s) or an honorarium X X Patent for a product referred to or X X marketed by a commercial organization. Investments in a pharmaceutical organization, medical devices company or communications firm. X Participating or participated in a clinical trial McMaster University Participated in periop research studies including VISION, POISE-2, MANAGE X

CSIM Annual Meeting 2017 The following presentation represents the views of the speaker at the time of the presentation. This information is meant for educational purposes, and should not replace other sources of information or your medical judgment. Learning Objectives: Understand the importance of perioperative risk assessment Review the utility of current risk stratification tools Examine the utility of BNP/nt-pro-BNP in the preoperative setting Understand the significance of the postoperative troponin elevation and develop an approach to management

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Case Mrs. B.W. 72 y/o F with significant OA Referred for upcoming total knee arthroplasty Cardiac risk factors DM, HTN, Chol, previous NSTEMI 2003 Otherwise asymptomatic, N vitals, N labs Meds: ASA, Atorvastatin, Coversyl, Bisoprolol OR date July 19, 2016

Case Mrs. B.W. What should be done next? 1. Send for cath 2. Take pt straight to the OR, no other consult required 3. Cancel surgery too high risk 4. Consider for a perioperative consult by medicine and/or cardiology teams

Is the preoperative consult useful?

Scope of problem Worldwide >200,000,000 major noncardiac surgical procedures annually 1:20 suffer myocardial injury/infarction or cardiac arrest/death within 30 days Perioperative cardiac complications account for 1/3 of perioperative deaths

Is the preoperative consult useful?

Yes! Is the preoperative consult useful? 1. Patients: ethical obligation to patients to give accurate risk assessment for informed decision making 2. Physicians: Gauge CV risk to guide management Further testing if needed Instructions re: medications Postop monitoring Shared care model

Good Pre-op Consults Specify: 1. Clear estimation of risk 2. Clear recommendation re: further testing 3. Clear recommendations for medications 4. Clear direction as to degree of post op monitoring i.e. ward bed w tele vs CCU/ICU/Step down bed, trops 5. Clear communication of who will do what

Risk Scores RCRI most validated; simplest to use CAD, stroke, CHF, DM, high risk surgery, Creatinine Does not take into account emergency surgeries underestimates cardiac risk by 50% NSQIP likely superior to RCRI Requires an online calculator Underestimates risk as routine troponin screening not done All risk scores will underestimate in >40% pts Limited mobility so pts won t manifest symptoms

CCS Recommendation When evaluating cardiac risk, we suggest clinicians use RCRI over other available clinical risk prediction scores Conditional recommendation low-quality evidence

Revised Cardiac Risk Index Variables Pts Hx of IHD 1 Hx of CHF 1 Hx of CVD 1 Insulin for diabetes 1 Crt >177 µmol/l 1 High-risk surgery 1 Total RCRI points Risk of MI, cardiac arrest, or death 30 days after surgery 95% CI 0 3.9% 2.8%-5.4% 1 6.0% 4.9%-7.4% 2 10.1% 8.1%-12.6% 3 15.0% 11.1%-20.0% * based on high-quality external validation studies

Is Non-Invasive Testing Useful? Current guidelines: Pts with low functional capacity Pts with risk of MI/death 1% When result will change management Stress Nuclear and Stress Echo most common 9% of adults age 40 with int/high risk tested

Pharmacological stress echocardiography and radionuclide imaging Several studies, mostly small sample size and small number of events Low quality of evidence most retrospective, few reported risk adjusted associations No study adequately assessed incremental value of stress tests over well-established perioperative cardiac risk factors (e.g., RCRI)

CCS Recommendations We recommend against performing preoperative exercise stress test, pharmacological stress echocardiography, or preoperative radionuclide imaging to enhance perioperative cardiac risk estimation

Is Cardiac CT Angiography Useful?

VISION CCTA Prospective cohort study 12 centers in 8 countries Evaluated whether preop CCTA enhances perioperative risk prediction in 955 at-risk patients Physicians were blinded unless LM detected Systematic Postop Trop monitoring Primary outcome - CV death and nonfatal MI 74 patients (7.7%) within 30 days of surgery

Interpretation of VISION CCTA results Although CCTA findings improve risk estimation for patients who will suffer periop CV death or MI CCTA findings are more than 5 X as likely to lead to inappropriate overestimation of risk among patients who will not suffer these outcomes

CCS Recommendation We recommend against performing preoperative coronary CT angiography to enhance perioperative cardiac risk estimation Strong recommendation, moderate-quality evidence

Biomarkers NT pro-bnp

Individual data M-A of 2179 patients 235 suffered death or MI within 30 days after noncardiac surgery Preop NT-proBNP 300 ng/l or BNP 92 ng/l strongest independent preop predictor of death/mi OR, 3.40; 95% CI, 2.57-4.47 Compared to preop clinical model preop natriuretic peptide improved risk estimation among patients who did and did not suffer primary outcome In sample of 1000 patients overall absolute NRI is 155 patients

NT-proBNP/BNP Risk of death or MI at 30 days after noncardiac surgery, based on patient s preoperative NT-proBNP or BNP Test result Risk estimate 95% CI NT-proBNP <300 ng/l or BNP <92 mg/l 4.9% 3.9% - 6.1% NT-proBNP value 300 ng/l or BNP 92 mg/l 21.8% 19.0% - 24.8% compared to RCRI, preop NT-proBNP/BNP results improved risk classification in 155 patients in 1000 patient sample based on risk categories <5%, 5-10%, >10-15%, >15%

Biomarkers NT pro-bnp Compared to imaging, NT pro-bnp More accurate Less expensive Convenient and faster due to availability of point of care NT pro-bnp assays due to cost differential b/w NT pro-bnp and consult may have role in determining who needs preop consult

CCS Recommendation We recommend measuring NT-proBNP or BNP before noncardiac surgery to enhance perioperative cardiac risk estimation in patients 65 years of age, 45 to 64 years of age with significant cardiovascular disease, or who have RCRI score 1 Strong recommendation, moderate-quality evidence

Troponin monitoring POISE Trial (8351 patients) 65% of patients suffering perioperative MI do not experience ischemic symptoms Presence or absence of signs/symptoms does not change risk 30-day mortality symptomatic MI: aor 4.76 (95% CI, 2.68-8.43) asymptomatic MI: aor 4.00 (95% CI, 2.65-6.06)

VISION Study (Botto 2014) Prospective international cohort study 15,065 in-hospital noncardiac surgery patients TnT measured postop days 1,2,3 MINS Criteria TnT 0.03 ng/ml due to myocardial ischemia death at 30 days: MINS - 9.8%, No MINS - 1.1% 84% MINS asymptomatic undetected without troponin monitoring Asymptomatic perioperative TnT elevations adjudicated as myocardial injuries due to ischemia that did not fulfill Universal Definition of MI were also associated with increased risk of 30-day mortality ahr, 3.30; 95% CI, 2.26 4.81

Recommendation We recommend obtaining daily troponin measurements for 48 to 72 hours after noncardiac surgery in patients with baseline risk >5%* for cardiovascular death or nonfatal MI at 30 days after surgery Strong recommendation, moderate-quality evidence * Patients with an elevated NT-proBNP/BNP measurement before surgery or, if there is no NT-proBNP/BNP measurement before surgery, in those who have an RCRI score 1, age 45 to 64 years with significant cardiovascular disease, or age 65 years

Approach to MINS Look for and correct physiological abnormalities hypoxia, hypotension, tachycardia (if BP adequate), Hb if <70 If no signs of bleeding initiate ASA 81 mg daily Initiate or intensify Statin therapy

Postoperative management of complications ASA and statin in patients suffering myocardial injury after noncardiac surgery Prospective cohort study 415 noncardiac surgery patients who suffered postop MI ASA and statin at discharge reduced 30-day mortality ASA : aor 0.54 (95% CI, 0.29-0.99) Statin: aor 0.26 (95% CI, 0.13-0.54)

Recommendations We recommend initiation of long-term ASA and statin in patients who suffer myocardial injury or myocardial infarction after noncardiac surgery Strong recommendation, moderate-quality evidence

Conclusions 1. Current clinical risk scores underestimate risk in substantial proportion of patients Revised risk estimations for RCRI in new CCS guidelines Non-invasive testing probably adds little CCTA has net overall effect of putting more patients in wrong risk category 2. NT pro-bnp is more accurate, convenient, faster, and less expensive than non-invasive testing 3. Troponin are strong independent predictor of 30-day mortality after noncardiac surgery 85% of MINS patients asymptomatic (4 TH gen trop) Up to 93% asymptomatic with hs-trops 4. ASA and Statins reduce 30 day mortality in patients with MINS

CSIM Annual Meeting 2017 Special thanks to Dr. PJ Devereaux Scientific Leader, Perioperative Research Group, PHRI, McMaster University VISION, POISE 1, POISE 2 MANAGE, HIP ATTACK, VISION 2, POISE 3 Co-Chair, CCS Perioperative Guidelines

Comments and Questions

M-A of dipyridamole stress perfusion prior to vascular surgery

M-A of dipyridamole stress perfusion prior to vascular surgery Baseline risk = 7%

Is Non-Invasive Testing Useful? Limitations: Small studies, few events, clinicians not blinded Almost half used a retrospective design No evaluation independent prognostic value Few systematically monitored for MI None reporting net absolute reclassification

Net Absolute Reclassification Index how well a new model reclassifies subjects - either appropriately or inappropriately - as compared to an old model i.e. comparison of old model vs. old model + 1 new element RCRI alone vs. RCRI + non invasive test

Is Cardiac CT Angiography Useful?

Model with CCTA and RCRI - C=0.66 # of Patients HR 95% CI P RCRI scores 0 1 2 3 CCTA findings Normal Non-obst Obstructive Extensive obst 320 407 178 50 81 371 357 146 1.00 1.39 (0.74-2.61) 1.88 (0.94-3.79) 4.02 (1.80-8.98) 1.00 1.51 (0.45-5.10) 2.05 (0.62-6.74) 3.76 (1.12-12.62) 0.005-0.300 0.076 <0.001 0.014-0.509 0.238 0.032

Net reclassification index Models for 30 day probability of CV death and MI Model that included CCTA findings Patients who had an event Patients who did not have an event RCRI only <5% 5-15% >15% <5% 5-15% >15% <5% 5 10 0 191 114 0 5-15% 0 41 7 47 453 37 >15% 0 1 10 0 10 29 NRI for those who had event: 21.6% 95% CI 10.4-32.9) p<0.001 NRI for those who did not have event: -10.7% (-13.9- -7.5) p<0.001 Overall NRI: 11% (-0.73, 22.64), p=0.066

Net reclassification index Models for 30 day probability of CV death and MI Model that included CCTA findings Patients who had an event Patients who did not have an event RCRI only <5% 5-15% >15% <5% 5-15% >15% <5% 5 10 0 191 114 0 5-15% 0 41 7 47 453 37 >15% 0 1 10 0 10 29 17 pts appropriately reclassified 1 pt inappropriately reclassfied Net = 17-1 =16

Net reclassification index Models for 30 day probability of CV death and MI Model that included CCTA findings Patients who had an event Patients who did not have an event RCRI only <5% 5-15% >15% <5% 5-15% >15% <5% 5 10 0 191 114 0 5-15% 0 41 7 47 453 37 >15% 0 1 10 0 10 29 17 pts appropriately reclassified 57 pts appropriately reclassified 1 pt inappropriately reclassfied 151 pts inapprop. reclassified Net = 17-1 = 16 Net = 57-151 = -94

CCS Recommendation We recommend against performing preoperative coronary CT angiography to enhance perioperative cardiac risk estimation Strong recommendation, moderate-quality evidence