Postoperative Troponin Screening: a Cardiac Cassandra?

DOI: 10.1161/CIRCULATIONAHA.113.003195

1

Postoperative Troponin Screening: a Cardiac Cassandra?

Running title: Beckman; Troponin: Barometer or Weathervane?

Joshua A. Beckman, MD, MS

Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA

Address for Correspondence:

Joshua A. Beckman, MD, MS

Cardiovascular Division

Brigham and Women’s Hospital

75 Francis Street

Boston, MA 02115

Tel: 617-525-7053

Fax: 617-232-2749

E-mail: [email protected]

Journal Subject Codes: Diagnostic testing:[33] Other diagnostic testing

Key words: surgery, surveillance, troponin T, myocardial infarction, Editorial

Cardiovascular Division, Brigham and Women’s Hospital, Boston, MAMAA

AAdAdddrdress for r CoCoCorrrrrresspopopondndndennencecee:::

JooJoshhhuau A. Beeckmamaman, MMMDDD, MMMSSS

CaCardrdrdioioiovavavascscscululu arar DDDivivvisissiioionnn

BBriighham and d WoWomemen’n’s s HoHospsppititalal

75 F i S

by guest on February 12, 2018http://circ.ahajournals.org/

Dow

nloaded from

http://circ.ahajournals.org/


2

The cardiovascular management of the patient undergoing non-cardiac surgery has been in

evolution for the last 35 years. Over this time frame, two secular trends have advanced in parallel

but provided contrary practice implications for the care of the surgical patient. First,

cardiovascular event rates have been dropping significantly over time. In 1977, Goldman and

colleagues created a risk evaluation system that predicted a 22% rate of “life-threatening”

cardiovascular events and more than 50% mortality in the highest risk group 1 in 1001 patients

undergoing surgery. These rates of events have dropped each decade since significantly. Finks

and colleagues reported 2 years ago a mere 2.8% national mortality rate for open abdominal

aortic aneurysm repair; the exemplar of routine, high-risk surgery 2. These numbers were

recapitulated world-wide for high-risk patients undergoing noncardiac surgery in the

PeriOperative ISchemic Evaluation (POISE) trial 3. Improvements in surgical and anesthetic

techniques, perioperative medical therapy, and intensive care have each participated in the

significant improvement in outcomes.

Second, the sensitivity of testing to detect evidence of cardiovascular disease or ischemia

has increased dramatically. In this same time frame, risk assessment has evolved from stress

testing, to nuclear – vasodilator testing, inotropic echocardiographic assessment, cardiac

magnetic resonance imaging, and positron emission tomographic (PET) scanning.

Counterintuitively, the ability to accurately detect smaller and smaller amounts of disease has not

improved post-operative cardiovascular event prognostication. Indeed, the positive predictive

value for each of these modalities in predicting a cardiovascular event remains below 20% 4. The

poor performance may be attributed to two components. First, improvements in disease detection

fosters inclusion of patients previously deemed healthy by less sensitive modalities. Indeed, it is

the specific coronary heart disease detection improvement that undermines its prognostic value

ecapitulated world-wide for high-risk patients undergoing noncardiac surgery iinn n thhhee

PeriOperative ISchemic Evaluation (POISE) trial 3. Improvements in surgical and anesthetic

eechchhnininiqququesess,, peperiopopopeererative medical therapy, and ininntetennsive care havevee eacach h h ppparticipated in the

iiignnnifi icant immprprovovovememeenent tt ininin oooutututcocomememes.s.

SeSecococondnnd,, tththee e sesensnsititivivitittyy y ofofof tttesesestitinngng ttto oo ddedetetetectctt eevvvidddenenncecece of f f cacacardrddioioiovavaascccululararar dddisiseaeaeassese ooorr iisischchhememmiai

has increased d drdrdramammatata iciccalala lylyy.. InInIn tthihihiss s sasasamememe tttimimime e e frfrframamme,e,e rrisiskk k asasassesesessssssmemm ntntnt hhhasasas eeevovovolvlvvededd fffrororom mm stress


Dow

nloaded from



3

in the stable patient by diminishing the risk of the group with a “positive study.” Second, ever-

dropping event rates largely render the prognostic value of these tests moot. A three-fold hazard

ratio in the setting of a 1-3% surgical mortality provides little insight into patient selection for

higher level therapies beyond medical therapy. Because of the overall low mortality and the

limited value of noninvasive testing to clarify outcome and need for preoperative coronary artery

revascularization 5, there has been an increase in effort to find patients at heightened risk post-

operatively to stave off severe adverse events. Over the last decade, much of this effort has

focused on biomarkers of myocardial injury, the cardiac troponins.

The troponin complex is co-located with tropomyosin on the actin filament and

participates in cardiac muscle contraction. The complex consists of three peptide components, T,

I, and C. The first two have been used in the measurement of myocardial injury whereas troponin

C, the calcium binding site, is not because of its shared location in skeletal muscle. Measurement

of troponin T was approved by the Food and Drug Administration in 1996 and its uptake into the

medical practice was rapid. Just 4 years later, the cardiology community made troponin the

preferred biomarker to diagnose myocardial infarction 6 as part of the guideline process. By

2007, troponin measurement became the de facto global standard when the first Universal

Definition of Myocardial Infarction was published 7. Over the last decade, the troponin use has

skyrocketed beyond the limited use for determining the presence or absence of an acute coronary

syndrome and become a nonspecific marker of illness. Indeed, the value of troponin in the

diagnosis of myocardial infarction may have reached its apex in 2001 with the publication of the

Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative

Strategy (TACTICS) study. The investigators showed that early invasive therapy was superior to

a conservative approach in patients presenting to the hospital with chest pain with a troponin T of

participates in cardiac muscle contraction. The complex consists of three peptidde e cooompmpponnonenenentstst ,, T,

, and C. The first two have been used in the measurement of myocardial injury whereas troponin

C,C, ttthehehe ccc lalalciciciumumum bbininindidid ng site, is not because of itss shshs aaared location ininn skeelelelettatal muscle. Measurement

off ttrroroponin T wawaas appprpprovovovededed bbbyyy ththe ee FoFoF ododd anddd DDDruggg AdAdmimim ninissts rraratitioonon iin n 1911 99696 aaandndnd iitstss uuptptp akaka eee iininttot the

memeedididicacacall prprpracacacttiticece wwwasas rrrapappidid. JuJuJuststst 444 yyyeaearrsrs lllatatatereer, thththee caaardrddioiololologygygy cccomomommumumuniniityty mmaadadeee trtropopopoooniinin ttthehe

preferred biomommarara kekeker r r totoo dddiaagngngnosoo e e e mymymyocoo ararardididialalal iiinfnfnfararrctctctioioonn 666 aaass s papapartrtrt ooof thththeee guguguidididelele ininne e prprprocococesee s. By


Dow

nloaded from



4

> 0.01 ng/ml but not without this troponin T elevation 8. This led to the wide adoption of

troponin in the standard evaluation of patients with chest pain or thought to be at risk of

myocardial infarction.

Subsequently, troponin has been measured in a wide variety of settings to provide

prognostic information in diseases that do not originate in the coronary arteries. Prognostic

information has been generated for diseases that originate with the heart, affect the heart, are

remote from the heart, and have extended to patients who aren’t acutely ill. Elevations in

troponin associate with worse outcomes in patients with myocarditis 9, congestive heart failure 10,

11, and cardiac contusions 12 showing the value of this biomarker in a broad range of cardiac

disease. Troponin release provides significant prognostic information for pulmonary disease,

presumably because of its direct vascular coupling with the right ventricle. For example, many

studies have shown that troponin release during pulmonary embolism is a marker of severity and

adverse prognosis 13-15. Similarly, elevations in troponin during chronic obstructive pulmonary

disease exacerbation are associated with a greater need for ventilator support and worse long-

term survival 16. The release of troponin is thought to result from a direct increase in right

ventricular overload and right heart strain.

Perhaps more impressively, release of cardiac troponin has become sensitive enough to

act a barometer of the severity of illness unrelated to the heart. Patients with septicemia who

have measurable troponin levels suffer worse outcomes than those who do not, even after

adjustment for other prognostic markers 17. Similarly, the release of troponin predicts poorer

outcomes in patients admitted with subarachnoid hemorrhage 18-20. More recently, investigators

have shown that troponin release may occur in the absence of overt illness and provide

prognostic data for outcomes in the non-hospitalized person. Using a high-sensitivity troponin T

disease. Troponin release provides significant prognostic information for pulmonnnaryryy dddisisiseaeaeasesese,,

presumably because of its direct vascular coupling with the right ventricle. For example, many

ttududdieieiesss hahahaveveve ssshoownwnwn that troponin release during pppulullmonary embolollisi m m isisis aa marker of severity and

addvveverse prognonosisis s 13-3-15151 . SiSiSimimimilalalarlrly,y, eelelel vvvatttionsss iinn troooppponiniinn n duduuriinng g chchrooniniicc oobobstststruruuctctivivvee pupup lmlmmononaararyyy

didiseseseasassee e exexacacaceererbabaattioonon aaareee aasss oocociaiaiateteted d d wiwiththth aaa gggrereatatatererr nnneeeedd d fofoforr r veveentntn ilillatattororor ssupupuppopop rtrtrt aaandnd wwwoorssse lllononggg-rr

erm survivaal l 161616.. ThThThee e rerer lelel asasse e e ofofo tttrororopopoponiiin nn isisis ttthohohougugughththt tttooo reeesususultltlt fffroroom m m a a dididirererectctct ininncrcreaeaeasesese iiin n n rir ght


Dow

nloaded from



5

assay, investigators in the Dallas Heart Study have shown that among 3546 individuals aged 30

to 65 years enrolled between 2000 and 2002, 25% of the cohort had detectable troponin T 21.

Moreover, when the troponin level was greater than 0.0014 ng/ml, the hazard ratio for all-cause

death over the 6.4 years of follow up was nearly 5 five fold higher despite adjusting for age,

race/ethnicity, sex, diabetes, hypertension, hypercholesterolemia, low high-density lipoprotein

cholesterol level, current smoking, log-transformed values of high-sensitivity C-reactive protein,

and chronic kidney disease categories. Moreover, the troponin elevation across the range

predicted all-cause mortality and cardiovascular mortality similarly. And, therein, lies the

problem. Although certainly originating in the heart, when used to provide prognostic data

beyond cardiac-in-origin diseases, troponin elevation no longer provides cardiovascular

outcome-specific information. It becomes a nonspecific test of illness that requires interpretation

by setting. Indeed, the screening measurement of troponin post-operatively most resembles the

use of troponin in the Dallas Heart Study as a screening tool.

In this issue of Circulation, Van Waes and colleagues are to be commended for reporting

the largest single-center study of post-operative troponins yet published. The investigators

studied 2,232 consecutive intermediate to high risk noncardiac surgery patients aged >60 years

who underwent surgery in 2011 22. Of the total surgical population, all-cause mortality was 3%,

troponin T release was detected in 19%, and elevations predicted death in a dose-related manner,

consistent with past work. Also consistent with past work and similar to the Dallas Heart Study

was a stronger association with all-cause mortality than myocardial infarction. In this cohort,

myocardial infarction (based on the universal definition) was diagnosed in 10 subjects or 0.6% of

the total.

Other studies have demonstrated both a similar relationship between troponin elevation

beyond cardiac-in-origin diseases, troponin elevation no longer provides cardiovvaaascucuc lalalar r

outcome-specific information. It becomes a nonspecific test of illness that requires interpretation

byy sssetetettititingngg.. InInInddeededd,, tht e screening measurement ofofof trrooponin post-oopepp raatitiivevevelyl most resembles the

uuse ofo troponiin n inini tthehe DDalalallalalass HHHeaeartrtrt SSStutuuddyy as a screeeeenninnnggg totooool.

InIn ttthihihiss isissususue e e ofoff CCiCircrculullatatioioion,n,n, VaVaVann WaWaWaeses aaandndd cccololleleagagaguueuesss arara eee tototo bbeee cocoommmmmenene dedeedd d foorrr rrerepopoorrtiining

he largest siingngnglelel -c-ccenenenteteter r r sttudududy yy ofofof pppososost-t opopoperereratatativiviveee trtrtropopoponono ininns s yeyeyet t pupupublbb isisishehehed.d.d TTTheheh iiinvnvnvesesestititigagag tors


Dow

nloaded from



6

and mortality after surgery and the relative infrequency of myocardial infarction by the universal

definition in this setting 23, however, it is the Vascular Events In Noncardiac Surgery Patients

Cohort Evaluation (VISION) Study that puts the whole picture in perspective 24. The VISION

investigators measured troponin T levels 6 to 12 hours after surgery and on days 1, 2, and 3 after

surgery in patients older than 45 years who required at least a one-night stay in the hospital.

Overall, the 30-day mortality rate was 1.9% and troponin T was measurable in 11.6% of the

patients. Across a narrow range of troponin T elevation, the hazard for mortality rose quickly,

with a 10-fold mortality risk noted in patients with troponin elevations 0.30 ng/ml. Despite the

fact that the vascular death category included nontraditional elements like pulmonary embolism,

hemorrhage, and death from unknown causes, the number of vascular deaths remained smaller

than non-vascular deaths. The VISION investigators reported that increases in troponin T

predicted cardiovascular and non-vascular death equivalently. Thus, post-operative troponin

elevation has become a non-specific marker of hazard.

In this author’s opinion, practitioners underappreciate this lack of specificity of post-

operative troponin testing. For example, the authors of the Third Universal Definition of

Myocardial Infarction 25 recommend “routine monitoring of cardiac biomarkers in high-risk

patients, both prior to and 48–72 h after major surgery” because “most patients who have a

perioperative MI will not experience ischemic symptoms. Nevertheless, asymptomatic

perioperative MI is as strongly associated with 30-day mortality, as is symptomatic MI.” They

then go on to recommend close clinical scrutiny, but without any specific recommendation for

care. I favor an approach to testing as advocated by Laine 26 in posing certain questions prior to

ordering a test. First, will the test change the care of my patient? In the asymptomatic patient

without ECG changes, a troponin elevation does not predict any specific kind of death, thus the

hemorrhage, and death from unknown causes, the number of vascular deaths remmmaininnededd ssmamamallllllerer

han non-vascular deaths. The VISION investigators reported that increases in troponin T

prrededdicicicteteteddd cacacardrdrdioovavavascscular and non-vascular death hh eqeqequuivalently. Thhusuu , popooststst-operative troponin

ellevvvaation has bebecococomeme a nnnononon-s-s-sppepecicififif ccc mmamarrkerr oof haaazaaard.. .

InIn ttthihihiss auauuththhoror’’ss ooopipip niionono , prprpracacacttitittioioonenenersrrs uuundndn eererapapa pprprecececiaiaiateee ttthihiis lalalackckck off f spsppecececififi iciccititityy y ofoff ppposost-t--

operative tropopoponononininn tttesese titit ngngn .. FoFoFor r exexexamamamplple,e,e, ttthehehe aaautututhohoorsrsr oof thththeee ThThThirirird d d UnUnnivivvererersasasall l DeDeDefififinininititiiononon of


Dow

nloaded from



7

test provides no direction for care and clinicians should continue to treat patients individually.

Second, what are the probability and potential adverse consequences of a false positive result?

For this, I would refer to the vanishingly small number of type 1 myocardial infarctions

diagnosed and worry that management for plaque rupture events (antiplatelet therapy,

anticoagulation, and possibly catheterization) would be provided for patients with hemodynamic

(type 2 myocardial infarction) events. None of these interventions is likely beneficial for the vast

majority of patients, particularly early after major surgery when the troponin is likely to be

elevated. As noted by Van Waes and the VISION investigators, the majority of troponin T

release occurs by the end of post-operative day 1, a high-risk period for bleeding. Third, is the

patient in potential danger over the short term if I do not perform this test? Although it is

certainly true that an elevation in troponin portends adverse outcome, the lack of specificity

concerning the mechanism of adverse outcome suggests that the test will not foster a change or

modification of therapy. In a small study of patients over aged 60 years undergoing emergency

orthopedic surgery, the addition of cardiovascular care to troponin positive patients did not affect

in-hospital cardiovascular complications or 1 year mortality 27. Most telling, however, is that the

cardiologists did little to alter care. No coronary angiography was performed and only 1 in 6

patients seen by cardiologists had the addition of aspirin, beta blockers, or both.

It is the author’s opinion that improvements in troponin T assay sensitivity have created a

condition in which the biomarker is so easily measured that it now culls out patients at higher

risk for any adverse event more than diagnoses cardiac-specific events. Indeed, one may suggest

that the results are similar to the Dallas Heart Study, but instead of free-living individuals, the

perioperative patient population represents an asymptomatic group exposed to surgical stress,

and the elevation in troponin similarly indicates a high-risk group for all-cause death. In the

patient in potential danger over the short term if I do not perform this test? Althoougugughh h iitit iiisss

certainly true that an elevation in troponin portends adverse outcome, the lack of specificity

cooncncncererernininingngng ttthehh mmmeecechah nism of adverse outcome sususuggggests that the ttesee t wiwiwillllll not foster a change or

mmoddidification oof ff thtt eererapappy... IIInnn aa a ssmsmalallll l sststuuddyyy off paaatiennnttss oveveverr agagageeded 6600 yeyeararss uunundedederrgrgoioinngng eememmerrgrgenennccyy

orrthththopopopedede icic sssuururgegeeryyy,,, ththhee adada diditititiononn ooof f f ccacarrddioioovavavascccululu ararr ccacareree tttooo trtrtroppponononininn ppposossiitiivivee papap titit enenntststs dididd nnnotot aaafffffece t

n-hospital cacardrdrdioioi vavavascscsculululara cccomomomplplplicicicatatatioi nsnsn ooor r r 11 yeyeyearara mmmoro tatatalililitytyty 272727.. MoMoMoststst tttelelelliliingngng,, hohohowewewevevever,r is that theee


Dow

nloaded from



8

absence of any demonstrated beneficial treatment strategy, the possibility of harm in applying the

standard treatment for type 1 myocardial infarction, and the potential to divert attention from a

true cause of adverse event (non-vascular morbidity) to a false one (myocardial infarction), the

author believes that routine measurement of troponin is more likely to cause harm than provide

benefit and should not be used as a screening modality.

Currently, low rates of overall perioperative mortality in the setting of guidelines based

care 28 have made risk prediction difficult and largely limited the task of risk assessment to

ferreting out patients with active cardiac conditions, severe pulmonary disease, or severe

underlying medical illness. These factors may or may not be related to the features seemingly

most predictive of troponin release, such as intra-operative hypotension, pre-operative

hypertension, and the presence of atherosclerosis 29-31. Studies are ongoing to determine response

strategies to elevations of troponin post-operatively, but until a specific strategy or treatment is

identified, the ontogeny of troponin testing makes unlikely patient benefit from its routine

measurement after noncardiac surgery.

Conflict of Interest Disclosures: Consulting: Ferring Pharmaceutical, Novartis Pharmaceutical, Merck Pharmaceutical, Astra Zeneca, and Boston Scientific. Board Membership: VIVA Physicians. Research Grants: Bristol-Myers Squibb References 1. Goldman L, Caldera DL, Nussbaum SR, Southwick FS, Krogstad D, Murray B, Burke DS, O'Malley TA, Goroll AH, Caplan CH, Nolan J, Carabello B, Slater EE. Multifactorial index of cardiac risk in noncardiac surgical procedures. N Engl J Med. 1977;297:845-850. 2. Finks JF, Osborne NH, Birkmeyer JD. Trends in hospital volume and operative mortality for high-risk surgery. N Engl J Med. 2011;364:2128-2137. 3. Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, Xavier D, Chrolavicius S, Greenspan L, Pogue J, Pais P, Liu L, Xu S, Malaga G, Avezum A, Chan M, Montori VM, Jacka M, Choi P. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (poise trial): A randomised controlled trial. Lancet. 2008;371:1839-1847.

most predictive of troponin release, such as intra-operative hypotension, pre-opererrattivivi ee

hypertension, and the presence of atherosclerosis 29-31. Studies are ongoing to determine response

ttraraatetetegigigieses ttto o o eeelevvvatatatioions of troponin post-operativvveelelyyy, but until a spppece ifficicc ssstrt ategy or treatment is

dddennntit fied, the e ononntooogegenynny oofff trtrtropoppononnininin tteessttiing mmmaaakesss uuunliiikekeelylyy patatieieentt bbennefefitit fffrororomm ititts ss rororouututinnnee

memeeasasa urururememenenenttt afaftteerr r nononncncarardid aacac sssurururgegegeryry..

CoConfnflilictct ooff InIntetererestst DDisisclclososurureses:: CoConsnsulultitingng:: FeFerrrriningg PhPhararmamaceceututicicalal NoNovavartrtisis PPhaharmrmacaceueutiticacall


Dow

nloaded from



9

4. Grayburn PA, Hillis LD. Cardiac events in patients undergoing noncardiac surgery: Shifting the paradigm from noninvasive risk stratification to therapy. Ann Intern Med. 2003;138:506-511. 5. McFalls EO, Ward HB, Moritz TE, Goldman S, Krupski WC, Littooy F, Pierpont G, Santilli S, Rapp J, Hattler B, Shunk K, Jaenicke C, Thottapurathu L, Ellis N, Reda DJ, Henderson WG. Coronary-artery revascularization before elective major vascular surgery. N Engl J Med. 2004;351:2795-2804. 6. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE, 3rd, Steward DE, Theroux P, Gibbons RJ, Alpert JS, Eagle KA, Faxon DP, Fuster V, Gardner TJ, Gregoratos G, Russell RO, Smith SC, Jr. Acc/aha guidelines for the management of patients with unstable angina and non-st-segment elevation myocardial infarction: Executive summary and recommendations. A report of the american college of cardiology/american heart association task force on practice guidelines (committee on the management of patients with unstable angina). Circulation. 2000;102:1193-1209. 7. Thygesen K, Alpert JS, White HD, Jaffe AS, Apple FS, Galvani M, Katus HA, Newby LK, Ravkilde J, Chaitman B, Clemmensen PM, Dellborg M, Hod H, Porela P, Underwood R, Bax JJ, Beller GA, Bonow R, Van der Wall EE, Bassand JP, Wijns W, Ferguson TB, Steg PG, Uretsky BF, Williams DO, Armstrong PW, Antman EM, Fox KA, Hamm CW, Ohman EM, Simoons ML, Poole-Wilson PA, Gurfinkel EP, Lopez-Sendon JL, Pais P, Mendis S, Zhu JR, Wallentin LC, Fernandez-Aviles F, Fox KM, Parkhomenko AN, Priori SG, Tendera M, Voipio-Pulkki LM, Vahanian A, Camm AJ, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Morais J, Brener S, Harrington R, Morrow D, Lim M, Martinez-Rios MA, Steinhubl S, Levine GN, Gibler WB, Goff D, Tubaro M, Dudek D, Al-Attar N. Universal definition of myocardial infarction. Circulation. 2007;116:2634-2653. 8. Cannon CP, Weintraub WS, Demopoulos LA, Vicari R, Frey MJ, Lakkis N, Neumann FJ, Robertson DH, DeLucca PT, DiBattiste PM, Gibson CM, Braunwald E. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein iib/iiia inhibitor tirofiban. N Engl J Med. 2001;344:1879-1887. 9. Freixa X, Sionis A, Castel A, Guasch E, Loma-Osorio P, Arzamendi D, Roig E, Perez-Villa F. Low troponin-i levels on admission are associated with worse prognosis in patients with fulminant myocarditis. Transplantation proceedings. 2009;41:2234-2236 10. Nishio Y, Sato Y, Taniguchi R, Shizuta S, Doi T, Morimoto T, Kimura T, Kita T. Cardiac troponin t vs other biochemical markers in patients with congestive heart failure. Circ J. 2007;71:631-635 11. Waxman DA. Troponin i is an independent predictor of all-cause mortality in hospitalized patients with congestive heart failure. Am Heart J. 2007;154:e27; author reply e29. 12. Rajan GP, Zellweger R. Cardiac troponin i as a predictor of arrhythmia and ventricular

7. Thygesen K, Alpert JS, White HD, Jaffe AS, Apple FS, Galvani M, Katus HA, NNNewewe bybyy LLK,K,, Ravkilde J, Chaitman B, Clemmensen PM, Dellborg M, Hod H, Porela P, Underwrwwooooo dd d R,R,R, BBBaxaxa JJ,Beller GA, Bonow R, Van der Wall EE, Bassand JP, Wijns W, Ferguson TB, Sttegeg PPPGGG, UUUrereretsttskykkyBF, Williams DO, Armstrong PW, Antman EM, Fox KA, Hamm CW, Ohman EM, Simoons ML, Poole-WiW lson PA, Gurfinkel EP, Lopez-Sendon JL, Pais P, Mendis S, Zhu JR, Wallentin LCC,,, FeFeFerrnrnananandededez-AvAvAvililes F, Fox KM, Parkhomenkko oo AAAN, Priori SG, TTTenndedederrara M, Voipio-Pulkki LM,VaVaVahahahanian AA, , CaCaC mmmmmm AAJ,J,J, DDDeee CaCateteteriririnana RR,, , DeDeanan VV, DiDiD ckststeieieinnn K,KK FiFiFillilippppppatatososos G, FuFuuncncnck-k-BrBrenenntatat nonono CC, HHelllleme ans I, KKririristtenensseen n n SDSDSD, , McMMcGGrGreegegooor KK, SSeSecchteeemmm U,U,, SSSililbbeber r S,S, TTTenndedederaaa MMM, WWiWidididimmsmskykyk PPP, ZZaZammomorano JJL,L,, MMMorrrais J,, Brereeneneer S,S HHHararrririnngn toonon R, MoMoM rrrrrowowow DDD, Limmm MM, MMMaarartitineneez-z-Riooos MMMAA,, StSteieieinhnhnhububu ll S,S,S, LLLevevvininnee GNGNGN,,, GiG bblblerrr WWWB,B,B GGGofofofff f DDD, TuTuT bbabarror MMM, , DDuDudededek k D,D,D AAAl-l--AAtAttatarr r NN.N. UUUnininiveerrrsaalal defifininititionn oof mymyoccarardidial iinfn ararctctioion.n Circcululatatioionn. 202 077;1;11616:2:263634-26265353..

88 CCanannononn CPCP WeWeinintrtrauaubb WSWS DeDemomopopoululosos LLAA VVicicararii RR FFrereyy MJMJ LaLakkkkisis NN NeNeumumanannn FJFJ


Dow

nloaded from



10

dysfunction in trauma patients with myocardial contusion. J Trauma. 2004;57:801-808; discussion 808. 13. Giannitsis E, Muller-Bardorff M, Kurowski V, Weidtmann B, Wiegand U, Kampmann M, Katus HA. Independent prognostic value of cardiac troponin t in patients with confirmed pulmonary embolism. Circulation. 2000;102:211-217. 14. Kucher N, Wallmann D, Carone A, Windecker S, Meier B, Hess OM. Incremental prognostic value of troponin i and echocardiography in patients with acute pulmonary embolism. Eur Heart J. 2003;24:1651-1656 15. Binder L, Pieske B, Olschewski M, Geibel A, Klostermann B, Reiner C, Konstantinides S. N-terminal pro-brain natriuretic peptide or troponin testing followed by echocardiography for risk stratification of acute pulmonary embolism. Circulation. 2005;112:1573-1579 16. Martins CS, Rodrigues MJ, Miranda VP, Nunes JP. Prognostic value of cardiac troponin i in patients with copd acute exacerbation. Neth J Med. 2009;67:341-349. 17. John J, Woodward DB, Wang Y, Yan SB, Fisher D, Kinasewitz GT, Heiselman D. Troponin-i as a prognosticator of mortality in severe sepsis patients. J Crit Care. 2010;25:270-275. 18. Naidech AM, Kreiter KT, Janjua N, Ostapkovich ND, Parra A, Commichau C, Fitzsimmons BF, Connolly ES, Mayer SA. Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage. Circulation. 2005;112:2851-2856.

19. Ramappa P, Thatai D, Coplin W, Gellman S, Carhuapoma JR, Quah R, Atkinson B, Marsh JD. Cardiac troponin-i: A predictor of prognosis in subarachnoid hemorrhage. Neurocrit Care. 2008;8:398-403. 20. Sandhu R, Aronow WS, Rajdev A, Sukhija R, Amin H, D'Aquila K, Sangha A. Relation of cardiac troponin i levels with in-hospital mortality in patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Am J Cardiol. 2008;102:632-634 21. de Lemos JA, Drazner MH, Omland T, Ayers CR, Khera A, Rohatgi A, Hashim I, Berry JD, Das SR, Morrow DA, McGuire DK. Association of troponin t detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010;304:2503-2512.

22. van Waes JAR, Nathoe HM, de Graaff JC, Kemperman H, de Borst G, Peelen LM, van Klei WA. Myocardial injury after noncardiac surgery and its association with short-term mortality. Circulation. 2013;127:XX-XXX. 23. Weber M, Luchner A, Manfred S, Mueller C, Liebetrau C, Schlitt A, Apostolovic S, Jankovic R, Bankovic D, Jovic M, Mitrovic V, Nef H, Mollmann H, Hamm CW. Incremental value of high-sensitive troponin t in addition to the revised cardiac index for peri-operative risk stratification in non-cardiac surgery. Eur Heart J. 2013;34:853-862.

17. John J, Woodward DB, Wang Y, Yan SB, Fisher D, Kinasewitz GT, Heiselmmman nn DD.D. TTTrororopopop nninas a prognosticator of mortality in severe sepsis patients. J Crit Care. 2010;25:2:2707070 2-2-2757575.

18. Naidech AM,, Kreiter KT, Janjua N, Ostapkovich ND, Parra A, Coommichau C, Fitzsimmons BFBF,,, CoCoConnnnololollylyly ES,S,S MMMayer SA. Cardiac troponin elelelevevvation, cardiovvasaa cuulalalarr r mom rbidity, and outcomeafafftteterrr subarachchchnonoididid hhememmororrrhrhrhagage.e.. CiCiC rcrcululatatioionn.. 202005055;1112:2:228585851-11 288855656..

19199. RRaR mapppa a P, TThhhataai DDD, CCCopopplin n W,W,W GGGeeellmmanann S, CCararhuhuuapapapomomma JRRR,, Quaahah R,R, AAAtkkinsssonnn BBB, MMarrrshhh JDDD. CaCaCardrdiaiacc c trtrtropoppononninin--ii: AA A prp edede icicictototor r r ofof ppprororogngngnosssisisi iiinn susubababarararachcchnononoididd hhhemememooorrrhrhagagge.e. NeNeeurururoccrrrit t t CaCaarere.. 200808;8;8 3:39898-40303.

2020 SaSandndhuhu RR ArArononowow WWSS RRajajdedevv AA SSukukhihijaja RR AmAminin HH D'D AqAquiuilala KK SaSangnghaha AA ReRelalatitionon ooff


Dow

nloaded from



11

24. Devereaux PJ, Chan MT, Alonso-Coello P, Walsh M, Berwanger O, Villar JC, Wang CY, Garutti RI, Jacka MJ, Sigamani A, Srinathan S, Biccard BM, Chow CK, Abraham V, Tiboni M, Pettit S, Szczeklik W, Lurati Buse G, Botto F, Guyatt G, Heels-Ansdell D, Sessler DI, Thorlund K, Garg AX, Mrkobrada M, Thomas S, Rodseth RN, Pearse RM, Thabane L, McQueen MJ, VanHelder T, Bhandari M, Bosch J, Kurz A, Polanczyk C, Malaga G, Nagele P, Le Manach Y, Leuwer M, Yusuf S. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307:2295-2304. 25. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, Katus HA, Lindahl B, Morrow DA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S. Third universal definition of myocardial infarction. Circulation. 2012;126:2020-2035. 26. Laine C. High-value testing begins with a few simple questions. Ann Intern Med. 2012;156:162-163. 27. Chong CP, van Gaal WJ, Ryan JE, Profitis K, Savige J, Lim WK. Does cardiology intervention improve mortality for post-operative troponin elevations after emergency orthopaedic-geriatric surgery? A randomised controlled study. Injury. 2012;43:1193-1198. 28. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF, Smith SC, Jr., Jacobs AK, Adams CD, Anderson JL, Antman EM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Page RL, Riegel B. Acc/aha 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: Focused update on perioperative beta-blocker therapy: A report of the american college of cardiology/american heart association task force on practice guidelines (writing committee to update the 2002 guidelines on perioperative cardiovascular evaluation for noncardiac surgery): Developed in collaboration with the american society of echocardiography, american society of nuclear cardiology, heart rhythm society, society of cardiovascular anesthesiologists, society for cardiovascular angiography and interventions, and society for vascular medicine and biology. Circulation. 2006;113:2662-2674. 29. Wax DB, Porter SB, Lin HM, Hossain S, Reich DL. Association of preanesthesia hypertension with adverse outcomes. J Cardiothorac Vasc Anesth. 2010;24:927-930. 30. Nagele P, Rao LK, Penta M, Kallogjeri D, Spitznagel EL, Cavallone LF, Nussenbaum B, Piccirillo JF. Postoperative myocardial injury after major head and neck cancer surgery. HeadNeck. 2011;33:1085-1091. 31. Alcock RF, Kouzios D, Naoum C, Hillis GS, Brieger DB. Perioperative myocardial necrosis in patients at high cardiovascular risk undergoing elective non-cardiac surgery. Heart. 2012;98:792-798.

26. Laine C. High-value testing begins with a few simple questions. Ann Intern MMededed..2012;156:162-163.

27. Chong CP, van Gaal WJ, Ryan JE, Profitis K, Savige J, Lim WK. Does cardiology ntervention impprove mortality for post-operative troponin elevations after emergency

orrththhopopopaaeaedididic-c-c gggeririatatatririr c surgery? A randomised coontnntrooolled study. Innjujuj ryy.. 202020121 ;43:1193-1198.

2288. FFleisher LLA,A,A BBBecckmkmkmananan JJJA,A,A, BBroroowwnwn KKKA, CCCaaalkinnnss H, CCChahaikiki ofof EEE, FlFleieiissschmhmhmananann n KEKEKE, FrFrF eeeemmamannn WKWKWK, , Froehllicich JJBB,, Kaaasppper EEEKKK, KKerrststs eenn JJR, RRiiegeeel BB, , RoRoRobbbbbb JJJF, SSmmmith SCC,C, JJJr..,, JaJ cooobbss AAAKKK, AdAddamamamss s CDCDD, , , AnAAnddederrsrsononn JJL,L,L AAntntn mamaman nn EMEMEM, , FaFaFaxxxon nn DPDPDP, FuFuuststererer VVV, HaHaHalplperererinin JLL,L, HHHiriratata zkzkka a a LFLFF, HHuHunnnt SSSAALytltle e BWBW, , NiN shshimmurura a R, PPagge e RLRL, Riegelel BB.. AcAcc/c aha a 20200606 gguiuideelilinene uupddata ee onon pperioiopep raratitiveve cardiovascullararar eeevavaaluluuatattioioon fofofor r r noooncncn ararardidiacaca sssurururgegegeryryry:: FoFoFocucusesesed d d upupupdadadatetet ooon n n pepeperiririopopopeerararatititiveveve bbbete a-blocker hhererapapy:y: AA rrepeporortt ofof tthehe aamemeriricacann cocollllegegee ofof ccaardrdioiolologygy/a/amemeriricacann hehearartt asassosociciatatioionn tatasksk ffororcece oonn


Dow

nloaded from


Joshua A. BeckmanPostoperative Troponin Screening: A Cardiac Cassandra?

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2013 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation published online May 10, 2013;Circulation.

http://circ.ahajournals.org/content/early/2013/05/10/CIRCULATIONAHA.113.003195World Wide Web at:

The online version of this article, along with updated information and services, is located on the

http://circ.ahajournals.org//subscriptions/

is online at: Circulation Information about subscribing to Subscriptions:

http://www.lww.com/reprints Information about reprints can be found online at: Reprints:

document. Permissions and Rights Question and Answer available in the

Permissions in the middle column of the Web page under Services. Further information about this process isOnce the online version of the published article for which permission is being requested is located, click Request

can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.Circulation Requests for permissions to reproduce figures, tables, or portions of articles originally published inPermissions:


Dow

nloaded from

http://circ.ahajournals.org/content/early/2013/05/10/CIRCULATIONAHA.113.003195

http://www.ahajournals.org/site/rights/

http://www.lww.com/reprints

http://circ.ahajournals.org//subscriptions/


Documents

Postoperative Troponin Screening: a Cardiac Cassandra?