Avoiding Thor’s Thunderbolt!

The Urologist’s Role in Managing the Peri-operative Risk of Cardio-Ischemic

and Embolic Events

Philip J. Walther, MD, PhD, MBA, FACS Professor of Urologic Surgery Duke U. School of Medicine

Disclosures: None Off-Label Recommendations: None

Philip J. Walther, MD, PhD, MBA, FACS

Myocardial Infarction Evolving Diagnostics

• 1970’s: Primarily Sxs and EKG changes • 1980’s: Developing cardiac biomarkers

– LDH –isoenzymes, CPK and then CPK-MB • 1990’s: Onset of troponin Dxtics, but criteria for

ischemic Sx and EKG ∆ still dominant • 2000’s: Greater sensitivity: 4th and 5th Gen

– 2017: 5th Gen cTnT just approved by FDA • Impact of Better Dx & Rx: ↓ mortality rate

– Fewer have STEMI than N-STEMI MI’s

Major Peri-Operative Cardiac Complications

• Account for at least 1/3 of perioperative deaths. • Challenge: Ischemic Sx masked by patient’s

obtundation (Eg. Narcotics) or misinterpreted coinciding symptoms (abd. incisional pain)

• Impact: • Substantial morbidity & prolonged hospitalization • Increased medical cost • Affects intermediate and long-term prognosis.

Deceppe E, et al: Canad. J. Cardiology 2017; 33, 17-32

Revised Cardiac Risk Index Computation: Components (1 point / component present)

Lee TH, et al: Circulation 100: 1043-9, 1999

Revised Cardiac Risk Index Validation Cohort

RCRI Class

Index Sum

Major Cardiac Complication

Rate* (%) I 0 0.4 II 1 0.9 III 2 6.6 IV >2 11.0

*V.Fib/Cardiac arrest, Complete heart block, acute MI, or Pulmonary Edema

Lee TH, et al: Circulation 100: 1043-9, 1999

Ann Internal Med 2011; 154: 523-8

Perioperative MI (PMI) after Non-Cardiac Surgery:

Characteristics and Short-Term Prognosis

• Of those who had MI, 65% did not have ischemic Sx

• 30-Day Mortality: – PMI-11.6%; no PMI-2.2%

• With ischemic Sx: 9.7% • Without ischemic Sx: 12.5%

• 8.3% had elevated cardiac markers only Devereaux PJ et al:

Ann Internal Med 2011; 154: 523-8

VISION Investigators JAMA 2012; 307:2295-304

• Prospective cohort study (15,133 pts) • Troponins drawn daily (POD 1,2,3)

– NOTE: 4th Gen cTnT was utilized • Clinical outcomes reviewed: 30-day

mortality was determined.

Postoperative Troponin and 30-Day Mortality

• Peak Troponin level correlated with risk of death within 30 d VISION Investigators

JAMA 2012; 307:2295-304

Kaplan-Meier Estimates of 30-Day Mortality Based on Peak Troponin T Levels

MINS

• Many surgical patients sustain myocardial injury perioperatively that will not satisfy diagnostic criteria for MI, but portend diminished survival outcomes.

• (M)yocardial (I)njury after (N)on-cardiac (S)urgery- defined as: myocardial injury detected by troponin -caused by ischemia (that may or may not result in necrosis), has prognostic relevance, and occurs with 30 days of surgery.

VISION Investigators. Anesthesiology 2014; 307:564-78

MINS: Clinical Outcomes

• Eight % of patients suffered MINS • 52.8% would not have fulfilled universal

definition of MI. • Only 15.8% of MINS experienced ischemic

symptoms. • Conclusion: MINS is common and is

associated with substantial mortality.

VISION Investigators. Anesthesiology 2014; 307:564-78

JAMA 2017; 317: 1642-51

• 21,842 participants • Outcome: Death within 30 d.: 266 (1.2%) • Protocol: • cTnT drawn postop: At 6-12 hr, D1, 2, 3 • If >14 ng/L, assessed for:

– Ischemic features (Sxs, EKGs) – Excluding sepsis, PE, AF

Post-Operative Complications Troponin Occurrence and 30-Day Mortality

Complication % Occurrence Deaths (% of Occurrence)

MINS 17.9 4.1 Major Bleeding 14.2 4.5 Sepsis 4.1 9.3 New Atrial Fib 1.2 10.6 Stroke 0.3 15.9 Pulmonary embolus 0.4 4.3 DVT 0.3 2.6 Pneumonia 1.8 9.4

VISION Study Investigators. JAMA 2017;317:1642-51

Post-Operative Complications Troponin Occurrence and 30-Day Mortality

VISION Study Investigators. JAMA 2017;317:1642-51

Brain (B-Type) Natriuretic Peptide (BNP)

• Synthesized as Pro-BNP. Released by cardiomyocytes with multiple stimuli: – Ischemia, stretch, inflammation,

neuroendocrine stimuli. – Inhibits renin ↓ Aldosterone

production Natriuresis – Causes vasodilation

Brain (B-Type) Natriuretic Peptide (BNP)

• Strongly prognostic of cardiac injury and decompensation. – N-terminal peptide (NT-ProBNP and BNP very

similar in prognostic value.) • Blood test is inexpensive.

Peri-Op Cardiac Risk Assessment /

Management for Elective Non-Cardiac Surgery: Canadian Cardiovascular Society Guidelines 2017

(Duceppe, 2017: Can. J. Card.)

Patient Population: (Surgery requiring overnight admission) • Age: 18-44 yrs + known

signif. CV (SigCV) disease* • Age: ≥ 45 yrs

Risk Stratification with Revised Cardiac Risk (Lee) Index

If: • ≥ 65 yrs and RCRI ≥ 1, • 45-64 yrs with Sig CV,

Draw BNP/NT-proBNP (Neg. / Threshold- NT-pro: <300 mg/L

BNP <92 mg/L)

If NOT: No further testing

necessary

If Neg: No

additional Routine Postop

monitoring

If Pos:

• EKG in PACU (? Troponin) • Daily troponin x 48-72 hrs • Consider in-hospital shared-

care management

* Sig. CV Disease: Known CAD,

CBVD, PAD, CHF, Severe PHTN,

Severe obstructive intra-cardiac abnormality

Anesth Analg 2014; 119:1053-63

• Retrospective, case-controlled study • Site: Paris, France • All patients aged >18 years who underwent

major vascular surgery 2005-8 • Note: All patients had 30d of enoxaparin

Therapy Intensification (TI) for Post-Operative Troponin Elevation

• Focus on 4 major drug groups: – Anti-platelet agents – Beta-blockers – ACE inhibitors – Statins

• 66 pts with Pos. cTp: – 43 had TI; 23- no change

Fourcrier A, et al.: Anesth Analg 2014; 119:1053-63

Therapy Intensification (TI) for Post-Operative Troponin Elevation

Fourcrier A, et al: Anesth Analg 2014; 119:1053-63

Gettysburg, 1863

THE “GOOD OLD DAYS”

SURGEON

THE “GOOD OLD DAYS”

Gettysburg, 1863 • Surgical therapeutic objectives

were straightforward. • Since the “tools of the trade” were

few (scalpel, saw, and thread), outcome expectations were limited.

• The surgeon was a HERO – when the patient lived!

• No one kept track of complications; they kept track of “SAVES”.

NOT the “GOOD OLD DAYS” Anymore!!

• Joint Commission inspections & mandates provide a regulatory framework for constant surveillance of physician practice patterns

• National Surgical Quality Improvement Program (NSQIP)

• Plaintiff Bar Filing Malpractice Torts

EVERY BUSY SURGEON’S NEMESIS

EMBOLUS

CMS considers Venous Thromboembolism

a preventable complication!!!

NOT the “GOOD OLD DAYS” Anymore!!

• Payors are now monitoring physician performance (scorecards”): – Complications – Length of Stay – Re-admission rates – Deaths!

• Since CMS considers venous thromboembolism a preventable complication, it becomes a major cost to the hospital– and ….

• SURGEON PRACTICE PATTERNS BECOME AN ISSUE!

DVT Occurrence Correlates in Tandem with No. of Risk Factors

Anderson FA, Spencer FA. Circulation 2003; 107:I9-I16

Risk of VTE in Perioperative Period

Bahl V, Et al: Ann Surg 2010; 251: 344

Radical Cystectomy: A Setup for VTE?

• Of GU cancer cases, highest rate of VTE • Independent risk for VTE • Contemporary VTE incidence: 2.9-24.4% • In pelvic surgeries, Gyn and Gen Surg

literature suggests that risk extends beyond discharge date.

Findings: • 6% were diagnosed with VTE (DVT only- 2.9%; PE only-

1.7%; Both-1.4%) • 55% were diagnosed after initial discharge (65% of PE, 50%

of DVT) • Of pts with VTE, 30-day mortality rate was 6.4%

J. Urol 191: 943, 2014

Observational retrospective study: 1,037 cystectomy patients Source: NSQIP data base of ACS

Timeframe of surgery: 2005-2011

Timing of Postoperative VTE Events

VanDlac AA, et al. J. Urol 191: 943, 2014

Median and Mean Time: 14d &15.2d, respectively

DVT Prophylaxis: Changing Patterns of Care-Need for New Paradigm?

• Large clinical experience (outside GU) has demonstrated risk of thromboembolism for several weeks after surgery (multiple abdominal sites)

• “Utilization Review” initiatives in late 1990’s: – Impact: substantially shorter postoperative hospital stays. – When used, postop inpatient DVT prophylaxis (SCD’s, ?

pharma) had a substantially shorter duration of use => potentially adverse outcomes

• Time for new paradigm? (Post-discharge prophylaxis!!) But if so, extent of duration?

• All 332 pts: Everyone- Enoxaparin 40 mg qd (starting 10-14 hrs preop) for 6-10 d => then randomized.

• Randomization: Placebo vs. Drug for 19-21 d. • Compression stockings but no SCD’s • All pts had venograms at 25d (after not earlier for

Sxs)

New Engl. J. Med. 346: 975, 2002

Prospective, Double-blind, Placebo-controlled Randomized Trial

DVT Prophylaxis-Postoperative Ortho LMWH (Enoxaparin) vs. Placebo

• Study: 100 pts undergoing hip surgery • Regimen: Randomization. Enoxaparin 30 mg

bid starting 12 hr postop x 14d (or discharge) • Monitoring: Daily 125I-Fb scans (confirmed by

venography if positive)

Turpie AGG, et al. et al. New Eng. J. Med. 315: 925, 1986

DVT Prophylaxis-Postoperative LMWH (Enoxaparin) vs. Placebo

Turpie AGG, et al.: New Eng. J. Med. 315: 925, 1986

(10.8%) (51.2%) ( 5.4%) (23.1%)

Caprini Method

of Risk

Stratifi-cation

Bahl V, et al: Ann Surg

2010; 251: 344

Bahl V, Et al: Ann Surg 2010; 251: 344

SHOCKING!!!

• 10,966 AUA members queried; 11% responded. • Question: FAMILIAR WITH RECOMMENDATIONS of the

AUA Best Practice Statement? • Yes 50.7% • No 19.4% • Unaware of AUA-BPS 29.9%

49.3% Sterious S, et al.: J. Urol. 190: 992 (2013)

DVT Prophylaxis: Technique

• Mechanical: – Early ambulation – Graduated compression stockings – Intermittent (sequential) pneumatic compression (SCD’s)

• Pharmacologic: – Low-dose unfractionated heparin (LDUF-H) – Indirect Factor X inhibitors:

• Low molecular weight heparin (WMWH)- Ex., enoxaparin • Synthetic- fondaparinux

– Vitamin K antagonists (VKA)- warfarin – Oral therapies: Factor IIa & Xa inhibitors (dabigatran,rivaroxaban) – Developmental: Anti-sense anti-Factor XI inhibitors

Stratifying Patient Risk of DVT: Intrinsic Patient Risk AND Type of Procedure

Risk Stratification

AUA Best Practice Statement-DVT Prophylaxis, 2008

Risk-Adapted VTE Prophylaxis: AUA-Best Practice Statement

*If patient >150 kg, consider Enoxaparin 40 mg q12h

AUA-BPS DVT Prophylaxis, 2008

“In selected very high-risk pts, consider post-discharge enoxaparin”