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Clinical Question:

  1. In patients presenting to Primary Care and the Emergency Department with acute chest pain, what is the accuracy and utility of a POC panel of cardiac markers compared to standard practice in diagnosing myocardial infarction? 
  2.  In patients presenting to Primary Care and the Emergency Department with acute chest pain, what is the prognostic value of a POC panel of cardiac markers compared to standard practice in predicting short-term (up to six-month) future cardiac events?

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Background, Current Practice and Advantages over Existing Technology:
Myocardial infarction (MI), ‘a heart attack’, is caused by myocardial ischaemia(1). Upon myocardial ischaemia, components of cardiac muscle are released into the blood stream(1). The detection of these biomarkers - cardiac troponin (cTn), myoglobin and creatine kinase MB isoenzyme (CK-MB) - form the foundation of MI diagnosis(2, 3).

Due to its high cardiac specificity(2), the National Institute for Health and Clinical Excellence (NICE) currently recommends testing of troponin I or T on initial presentation to hospital and again 10-12 hours after the onset of symptoms(4).  One limitation of this current protocol is troponin levels do not increase to a detectable level until 6 hours after the onset of symptoms(1), although limits of detection of troponin are diminishing with newer assays(5) (see concluding comments below). Myoglobin, however, is detectable within 1-2 hours of symptom onset(6), and generally returns back to normal levels within 24 hours of symptom onset(6). CK-MB, like troponin, is elevated approximately 6 hours after symptom onset, however, unlike troponin remains elevated for only 24-36 hours (troponin remains elevated for 7-10 days(6)). Therefore, it has been proposed that myoglobin could be useful for early detection of MI and both myoglobin and CK-MB could be useful for monitoring re-infarction(7).

Mortality risk has been strongly linked to time until treatment(8), with evidence showing a 1% mortality rate when treatment is implemented within 1 hour of an acute event, compared to 10-12% at 6 hours(8). It has been suggested that POC testing could facilitate more rapid treatment decisions. However, it must be noted that the improved detection limit and functional sensitivity has led to some literature suggesting highly sensitive troponins alone may soon be sufficient to rule in or out MI within an hour(5).     

Chest pain accounts for 700,000 attendances to Emergency Departments (ED) in England and Wales annually(9). Studies have suggested that up to 85% of these patients are not actually suffering from MI(6, 10, 11). Much time and money is spent stratifying these 700,000 patients(12). POC panels of all three cardiac markers could provide a result (predictive for actual risk of having an MI) more rapidly after onset of symptoms and thus confidently rule in or out MI. This ability to rule out in particular would allow patients who do not have an MI to be discharged, easing the financial burden and time pressure of current practice.

Details of Technology:
The available products that measure multiple cardiac markers are shown in the tables below. Qualitative devices only indicate if the specific biomarker is present in the sample at increased levels, whereas quantitative devices give a numerical value for each biomarker.

For the qualitative devices, the sample is applied to the cassette and results can be read directly.  The quantitative devices consist of one or more cassettes, where the sample is applied and then inserted into a bench-top analyser to obtain the results. The Nano-ditech and Anibiotech can be read as an individual cassette (qualitatively) or with a reader (quantitatively).

Qualitative POC devices:

 

Tn

CK-MB

Myo

Type of sample

Volume

Time (min)

FDA/CE approved

Individual cassette

WB

P

S

Decision point (EU)/ Cardiac STATus (US)

(Nexus Dx, Inc, USA)

~6 drops

15

Decision point: CE

Cardiac STATus: FDA

Yes

MI CK-MB/Myo/TnI (US)

(LifeSign LCC, USA)

120 µL

(3 drops)

15

CE

Yes

Instant view

(Alfa Scientific. Inc, USA)

 

4 drops

10

CE

Yes

Cardiac STATus

(Spectral Diagnostics Inc, Canada)

~6 drops

15

N/A

No

 
Quantitative POC devices

 

Tn

CK-MB

Myo

Type of sample

Volume

Time (min)

FDA/CE approved

Individual  cassette

WB

P

S

Triage Cardiac panel (Alere, UK) (*Alere acquired Biosite) 

 

250 µL

(~6 drops)

15

CE

 

Yes

RAMP

(Response Biomedical, Canada)

 

 

~6 drops

15

Both

No

Cobas h 232 system

(Roche Diagnostics Ltd., UK)

(T)

 

 

150 µL

(~4 drops)

8-12

CE

No

Stratus CS Acute Care Diagnostic System

(Siemens AG, Germany) *Formerly, Dade-Behring

 

 

~6 drops

14

FDA

No

AQT90 FLEX analyser

(Radiometer Ltd, England)   

(T+I)

 

~6 drops

10-20

N/A

Yes

Vidas Emergency Panel

(BioMerieux Ltd, UK)

250 µL

(~6 drops)

30

N/A

No

Pathfast

(Mitsubishi, Tokyo)

100 µL

(~3 drops)

16

N/A

No

 
Qualitative and Quantitative

 

Tn

CK-MB

Myo

Type of sample

Volume

Time (min)

FDA/CE

Individual cassette

WB

P

S

Nano-Check AMI Cardiac Markers

(Nano-Ditech Corp.,USA)

~6 drops

10-15

FDA

Yes

Cardiac marker tests (Anibiotech, Finland)

 

 

100 µL

(~3 drops)

15

CE

No

Tn: Troponin; CK-MB: Creatine Kinase MB; Myo: Myoglobin; Where no indication, troponin represents troponin I.

WB = Whole blood; P = Plasma; S = Serum; N/A: Not available

 Patient Group and Use:
Patients presenting to General Practice or Emergency Departments with acute chest pain suspicious of myocardial infarction 

Importance:
Although identification and management of risk factors and improved medication has resulted in a declining incidence of coronary heart disease (CHD), it remains the most common cause of death in the UK(12). Annually 1 in 5 male deaths and 1 in 10 female deaths can be attributed to CHD(12). It is estimated that CHD cost £1.8 billion in 2009(12). Of this, 56% is estimated to be due to inpatient hospital care(12). Additional cost, not included in the above estimation, can be attributed to lost working days (over £3 billion annually) and the burden of informal care (£1.7 billion in 2009)(12). Accumulatively, in 2009, the financial burden of CHD on the UK economy was estimated to be £6.7 billion(12). In the US, it is estimated to be “in excess of $10 billion”(10).  Much of this cost, morbidity and mortality can be off-set by early diagnosis, and consequential, early treatment. As well as accurate exclusion of patients presenting with chest pain, but not suffering a MI(8). In addition to management of patients with confirmed MI, there is also a considerable burden and cost of managing patients presenting to primary care, emergency ambulance services and emergency departments with chest pain(12). This is an extremely common clinical presentation, and requires usually immediate access to clinical services and the ability to safely risk stratify patients. By far the largest proportion of patients presenting in such settings will not have acute ischaemia as the cause of their chest pain(6), but clinical assessment alone, without the use of biomarkers, is not sufficient to make safe diagnostic decisions in the majority of patients.

Previous Research:
A total of 23 studies were identified of which 12 examined the Biosite/Alere Triage Cardiac Panel, 3 the Siemens Stratus CS Acute Care diagnostic system, 4 the Spectral Cardiac STATus and 1 each for the Response Biomedical RAMP, Radiometer AQT90 FLEX analyser and Nexus Cardiac STATus. All were based in the ED except one, which was based in an ambulance setting (Leshem-Rubinow et al 2011). 

We present the results grouped by POC device, and for each of these present existing research on diagnostic accuracy for MI, clinical utility, and prediction of future cardiac risk (at up to six months after initial chest pain event). Clinical utility is a broad term used to incorporate ‘practical’ aspects of Point-of-care testing (POCT). These practical outcomes vary between studies and can include Emergency Department length of stay (ED LOS), acceptance of POCT by ED staff, turnaround time (the time between blood sample taken and results returning) etc.  

The term ‘diagnostic study’ refers to the ability of the experimental POCT Multi-marker panel (MMP) protocol to acutely diagnose (rule in or rule out) an MI compared with the control protocol. Both the intervention protocol (POCT MMP protocol) and the control protocol (generally hospital-based laboratory) varied amongst studies.  The term ‘prognostic study’ refers to the experimental POCT MMP protocol to predict risk of short-term future cardiac events. Studies used varying follow up periods, but none more than 6 months.

Biosite/Alere Triage Cardiac Panel

The table below shows the studies that assessed the Biosite/Alere Triage Cardiac Panel. Together, these 12 studies examined 13 148 patients.

All studies included all three cardiac biomarkers (cTn, CK-MB, Myoglobin) except one, which examined only cTnI and Myoglobin(6). The table shows diagnostic, prognostic and performance studies as indicated.  

Study

Control: Central lab

No. of patients

Cut-off (μg/L)

Protocol

Sen

%

(95%CI)

Spec

%

(95%CI)

PPV

%

(95%CI)

NPV

%

(95%CI)

TnI

CK-MB

Myo

Than et al 2011(13)

Prognostic

Varied (Architect, Access Accu,  Vidas Ultra,  Vitros ECi ES,  E170,  Elecsys (2010),  Centaur Ultra)

3582

0.05

4.3 

108

Prognostic at 30 days

82.9% (79-86.2)

56% (54.3-57.7)

20.1% (18.2-22.0)

96.1% (95-96.9)

Aldous et al 2012(14)

Prognostic + Clinical utility

Architect

1000

0.05

4.3

108

Prognostic at 30 days

90.9% (86.7-94.0)

52.2 (50.9-53.2)

37.8 (36.1-39.1)

94.7% (92.3-96.5)

Birkhahn et al 2011(15)

Diagnostic + Clinical Utility

Hitachi Modular

Analytics system

151

0.1

4.3

150

Diagnostic at 2 hours

100% (74-100)

65% (57-73)

20% (11-32)

100% (96-100)

Meek et al 2012(16)

Diagnostic +

Clinical utility

 

Access Accu

258

0.08

6

107

Diagnostic at 2 hours

92.6% (74.2-98.7)

N=25/27

98.7% (95.9-99.7)

N=228/231

89.3% (70.6-97.2)

N = 25/28

99.1% (96.6-99.8)

N=228/230

Lee-Lewandrowski et al 2011(17)

Diagnostic

E170,

i-STAT (POC)

204

MMP:

0.05*

7.4

170

Diagnostic at present-ation (0 hours)

83%

78%

34%

97%

MMP: 0.39*

7.4

170

55%

80%

25%

94%

cTnI alone (Abbott): 0.08

 

 

63%

94%

58%

95%

cTnT (Roche)<0.03

 

 

88%

87%

48%

98%

Macdonald et al 2008(18)

Diagnostic +Prognostic

Elecsys 

100

0.05

4.3

107

Diagnostic at 2 hours

100%

86%

33%

100%

Prognostic at 30 days

86%

88%

38%

97%

Straface et al

2008(7)

Diagnostic

Dimension RxL 

5201

0.4

50% increase

Doubling

Diagnostic at 3 hours

98.0% (95.7-100.2)

99.8% (99.6-99.9)

92.4% (88.2-96.5)

99.9% ( 99.9-100.0)

Ng et al 2001(19)

Diagnostic + Clinical utility

Opus

1285

0.4

8.9

170

Diagnostic at 90mins

100%(CI not stated)

94% (CI not stated)

47%(CI not stated)

100%(CI not stated)

 

McCord et al 2001(6)

Diagnostic + clinical utility

AxSYM analyzer 

817

0.4 (CV:12%)

6 (CV:12%)

200 (CV:11%)

Diagnostic at 90mins

 

cTn and Myo only

96.7% (89-100)

53.1%(49-57)

15.2%(12-19)

99.6% (98-100)

 

Apple et al 1999(20)

Diagnostic

Stratus, Access, Opus 

192

0.4

4.3

107

0-<6h

52.5(37-68)

100(100-100)

 

 

6-<12h

53.1(35.8-70.4)

98.5(95.5-100)

12-<24h

61.4(47-75.8)

97.8(94.7-100)

>24-72h

60.4(50.4-70.5)

98.6(95.9-100)

Rathore et al 2008(21)

Prognostic

Not available

325

0.1

4.1

150

Prognostic at 6 months

85.7%( not stated)

96.5%(not stated)

92.3%(not stated)

 

Di Serio et al 2003(22)

Clinical utility

Dimensions RxL

33

0.19

4.3

107

*Clinical utility study

 

*The manufacturer’s recommended cut-off point is 0.39. However, the CV at this concentration of troponin is greater than 10% and thus does not meet with current acceptable guidelines. For this reason, this study used both cut off points (manufacturer’s: 0.39 and cut-off that meets guidelines: 0.05)(17)

Architect: Abbott Diagnostics; Access: Beckman Coulter, Inc. ; Vidas Ultra: bioMerieux; Vitros ECi ES: Ortho Clinical Diagnostics; E170: Hitachi Modular Analytics system, Roche Diagnostics; Elecsys (2010): Hitachi Modular Analytics system, Roche Diagnostics; Centaur Ultra: Siemens; i-STAT: Abbott diagnostics (POC device: cTnI only); Dimension RxL: Formerly Dade-Behring, now Siemens; AxSYM analyzer: Abbott Diagnostics; Stratus: Dade-Behring; Opus: Dade-Behring

The consistently high sensitivity and NPV supports the notion of using POCT as a ‘rule out’ device. 8 of the 9 diagnostic studies showed a sensitivity of greater than 82% (with 8 above 90%) and the NPV ranged from 94 to 100%. Conversely, the highly variable specificity and PPV (from 52.2 to 100% and 15.2 to 92.3%, respectively), helps confirm the minimal use for a POC device in ‘ruling in’ MI.  

Four prognostic studies(13, 14, 18, 21) examined the ability of cardiac biomarkers to predict future cardiac risk. Three of these used cardiac biomarker results to stratify chest pain patients into risk groups and assess major adverse cardiac events (MACE) over the following 30 days(13, 14), another study used the same methodology, however assessed over 6 months(21). All studies used all three cardiac biomarkers (cTn, CK-MB, Myoglobin) except one, which examined only cTnI and Myoglobin(6). The consistently high negative predictive value found across studies supports the notion that this device could be potentially employed as a risk stratification and rule out tool.    

Clinical utility
The measures of clinical utility predominantly revolved around time saved from POCT in comparison to routine practice. The savings from sampling to receiving results ranged from 47-59 minutes(6, 16, 22). Emergency Department Length of Stay (ED LOS) (median) was also decreased for both patients who were discharged (248 minutes saved) and admitted (124 minutes saved)(16) and an estimated 172(14) and 13650(15) bed days and patient care hours could be saved, respectively. 

One study also estimated that 22.8% of stress tests, 3% of angiography, and 4.6% of antiplatelet drugs currently used would be unnecessary under a POCT protocol(14).  Two studies showed the predictive value of POCT stratification, with only 1%(21) and 4%(13) of patients deemed low risk by POCT suffering a Major Adverse Cardiac Event (MACE) in the following 6 months and 30 days respectively. Importantly, POCT was well accepted by ED staff, with 90% supporting its on-going use(16).

 Siemens Stratus CS Acute Care Diagnostic System (Formerly Dade-Behring)

A small number of studies (3) were identified that examined the Siemens Stratus CS Acute Care POC MMP. Collectively, 3453 patients in total were assessed. The types of studies are indicated in the table below. 

Study

Control: Central lab

No. of patients

Cut-off

μg/L

Sen

%

(95%CI)

Spec

%

(95%CI)

PPV

%

(95%CI)

NPV

%

(95%CI)

Odds ratio (95%CI)

TnI

CK-MB

Myo

Caragher et al 2002(8)

Diagnostic at 24 hours +

Clinical utility

Stratus,  Hitachi, Axsym analyzer

205

0.1

5.6

85

100% (CI not stated)

100% (CI not stated)

97% (CI not stated)

100% (CI not stated)

 

Newby et al 2001(23)

Prognostic at 30 days

Varied (individually not reported)

1005

0.1

4

105

 

 

 

 

Mortality: 5.4 (2.8-10.4, p=0.0001)

MI: 9.6(4.9-19, p=0.0001)

 

Goodacre et al 2011(9)

Diagnostic at 4 hours +

Prognostic at 3 months +

Clinical utility

Centaur Ultra,  Elecsys,  iSTAT,  

Access Accu,

2243

0.03

5

2nd sample 25% higher

Diagnostic at 4 hours: Odds ratio: 3.81 (3.01 to 4.82, p < 0.001) 

Prognostic at 3 months: adjusted OR 1.31; 95% CI 0.78 to 2.20, p = 0.313).

 
One prognostic study showed the value of POCT in predicting future cardiac risk (assessed at 30 days) with an odds ratio of 5.4 (95% CI: 2.8-10.4, p=0.0001) and 9.6 (95% CI: 4.9-19, p=0.0001) for death and myocardial infarction after a positive POC result(23). The diagnostic accuracy appears strong, with the one diagnostic accuracy study showing exceptionally high sensitivity, specificity, PPV and NPV (100% for sensitivity, specificity and NPV, and 97% PPV)(8). However, since no confidence intervals were presented, this data should be interpreted with caution.       

Clinical utility
One study of clinical utility found that patients in the POC group were successfully discharged at a higher rate compared to standard-care group (358/1125 (32%) vs. 146/1118 (13%))(9). Further, the same investigators found a decrease in both median and mean LOS (p < 0.001 and p = 0.462 respectively) and a higher percentage of patients that had no inpatient days (p < 0.001) for the POC group(9).  The other clinical utility study compared the POC ‘time-to-result’ to standard care and found a 48 minute and 52 minute decrease for mean and median, respectively(8)

Spectral Cardiac STATus
A total of 4 studies were identified that compared the Spectral Cardiac STATus POC MMP with standard care; 2 studies focused on clinical utility, 2 on diagnosis.

Study

Control: Central lab

No. patients

Cut-off  

μg/L

Sen

%

(95%CI)

Spec

%

(95%CI)

PPV

%

(95%CI)

NPV

%

(95%CI)

TnI

CK-MB

Myo

Kratz et al 2002(24)

Diagnostic at 0 hours.

Elecsys

3369

1.5

5

50

Not reported

Not reported

76% (CI not stated)

Not reported

Hillis et al 1999(25) (*This study also included myosin light chain (MLC))

Diagnostic at 0, 4 and 8 hours.

Stratus

208

0.2

5

100

4hr: 88.0 (82.4 to 92.1)

57.7 (50.4 to 64.7)

23.7 (16.1 to 33.3)

97.0 (90.8 to 99.2)

8hr: 92.9 (88.2 to 95.8)

54.0 (46.9 to 61.0)

24.5 (17.3 to 33.6)

97.9 (92.0 to 99.6)

16hr: 92.9 (88.1 to 95.9)

51.5 (44.3 to 58.5)

23.6 (16.6 to 32.5)

97.8 (91.5 to 99.6)

24hr: 92.9 (88.0 to 95.9)

46.6 (39.4 to 54.0)

23.2 (16.3 to 31.9)

97.4 (90.9 to 99.5)

Mutrie 1999(26)

Clinical utility

Not reported

100

Not reported

Not reported

Not reported

*Clinical utility study only

Lee-Lewandrowski et al 2003(27)

Clinical utility

Not reported

369

Not reported

Not reported

Not reported

*Clinical utility study only

 
The strong NPV and sensitivity in the one diagnostic study (which these figures were reported in), support the other (above) research that POCT could work as an effective rule out tool. The PPV varied significantly between the two diagnostic studies (~23% vs. 76%). The contradictory cut-off levels used, year of study, the number of patients used in each study and/or the potentially variable methodological quality of each study could have influence these results.   

Clinical Utility
Two clinical utility studies(26, 27) found a decreased turnaround time of 45 minutes(27) and 30%(26) respectively. Further, both found that POCT was well accepted by ED staff(26, 27). Other notable findings include a 30 minute decrease in ED LOS(27) and 60% fewer “non-MI, non-unstable angina” patients admitted(26)

Radiometer AQT90 FLEX Analyser
One study was identified that assessed the Radiometer AQT90 FLEX Analyser. This Australian prognostic study stratified patients into risk groups according to their POC cardiac biomarker results and followed each group over 30 days to observe for MACE. The Radiometer POC MMP was outperformed by both the Radiometer POC cTnI and Beckman central laboratory.

Study

Control: Central lab

No. patients

Cut-off

μg/L

Sen

%

(95%CI)

Spec

%

(95%CI)

PPV

%

(95%CI)

NPV

%

(95%CI)

Area under ROC curve (95%CI)

TnI

CKMB

Myo

Cullen et al 2012(28)

Prognostic at 30 days

Access Accu, Radiometer cTnI (POC)

704

0.023

4.3 

108

Not available

Not available

Not available

Not available

POC MMP: 0.67 (0.61-0.72)

POC cTnI: 0.73 (0.68-0.78)

Central lab: 0.77 (0.72-0.82)

 
Nexus Decision Point (EU)/Cardiac STATus
One study was identified that assessed the Nexus Decision Point POC MMP. This study explored the use of POC MMP in a pre-hospital (ambulance) setting. Only 15 of the 641 negative POC patients suffered an MI in the following three days(29). The sensitivity (86.6%) and NPV (97.6%) supports the idea that POCT can be used as a ‘rule out’ tool(29). 

Study

Control: Central lab

No. of patients

Cut-off μg/L

Sen

%

(95%CI)

Spec

%

(95%CI)

PPV

%

(95%CI)

NPV

%

(95%CI)

TnI

CKMB

Myo

Leshem-Rubinow et al 2011(29)

Prognostic at 3 days

Not available

821

Not available

Not available

Not available

86.6% (CI  not specified)

83.3%(CI  not specified)

53.8%(CI  not specified)

97.6% (CI  not specified)

 
Guidelines and Recommendations
The European Society of Cardiology (ESC) and the American College of Cardiology (ACC) recently re-defined the diagnostic criteria for myocardial infarction(2, 3) – see appendix 1.  The British Cardiovascular Society (BCS), ESC, ACC, American Heart Association (AHA) and the National Academy of Clinical Biochemistry (NACB) recognize cTn (I or T) as the preferred biomarker for detection of MI(30, 31). 

In accordance to the ESC/ACC definition, NICE recommends testing of troponin I or T on initial presentation to hospital and again 10-12 hours after the onset of symptoms(4). The AHA guidelines and National Academy of Clinical Biochemistry (NACB) have similar recommendations (presentation and 8-12 hours after symptom onset, and 0-6h and 6-9 respectively)(32). Clinical settings in the UK and worldwide use different strategies to try ensure the most efficient and safe management of patients presenting with acute chest pain, given the need for two tests separated by several hours. As alternatives to simply keeping patients in the emergency department, some centres use short stay wards, dedicated chest pain units, or admit patients to the inpatient wards.

Further, there is recent and building evidence to suggest that single marker (troponin) rule out protocols are as effective as multi-marker protocols and will, most likely, become the standard(5, 33-35).  

According to the ACC/AHA, 60 minutes is the maximum acceptable turnaround time (for cardiac biomarker results to be returned), with 30 minutes the preferred(36, 37). Further, studies have recommended that “if standard laboratory testing exceeds a maximum 60-minute turn-around time (the average being 65–128 min) or 25% of decision time, then a POC device (with an average turn-around time of 15–26.5min) should be implemented”(32) 

Research Questions:

  1. In primary care, emergency ambulance and ED settings, what is the role of panels of (and single) POC cardiac biomarkers in the management of patients presenting with acute or subacute chest pain?  This research needs to focus on accuracy, clinical utility, cost effectiveness and comparison with existing clinical pathways. Particular issues include low prevalence of acute ischaemia among patients presenting with chest pain (particularly in primary care).
  2. Given the above, what is the role of emerging diagnostic cardiac biomarkers in the above settings? Highly sensitive troponins, Heart-type fatty acid binding protein (H-FABP), Brain natriuretic Peptide/N-terminal prohormone of brain natriuretic peptide (BNP/NT-proBNP), ischaemia modified albumin (IMA), Myeloperioxidase (MPO), soluble CD40 ligand (sCD40L) etc. 
  3. To what extent will increasingly sensitive Troponin assays replace the need for panels of biomarkers for the above indications and above settings?

Suggested next step:

  • There is a building amount of evidence to suggest that single-marker protocols – highly sensitive troponins – are as effective as any multi-marker strategy(5, 33-35). Because of this, future research attention should be directed towards highly sensitive troponin protocols.
  • Systematic review on the diagnostic accuracy and utility of POC panel of and single cardiac markers in patients presenting to ED and Primary care with acute chest pain.

Expected outcomes:

  • Acute chest pain is a common presentation in primary care, ambulance and ED settings, and typically requires biomarkers to safely and accurately rule in and rule out acute ischaemia. The main limitation in primary care settings is the need to have two tests taken several hours apart, which is generally not feasible in primary care. This could be transformed either by the use of single tests or panels with sufficiently high rule out value on single samples, or by incorporating biomarker results with clinical information (typically available in primary care), to enhance prediction.
  • For the ED setting, where chest pain is also a common presentation, POCT could improve management of acute chest pain by reducing time to obtain results and offer one, rather than two tests separate by at least 6 hours. These two advantages could improve patient management via more rapid rule in/out protocols and potentially offer a more cost effective protocol.

References:
1.             Kumar A, Cannon CP. Acute coronary syndromes: diagnosis and management, part I. Mayo Clinic proceedings Mayo Clinic. 2009 Oct;84(10):917-38. PubMed PMID: 19797781. Pubmed Central PMCID: PMC2755812. Epub 2009/10/03. eng.
2.             Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD. Third universal definition of myocardial infarction. European heart journal. 2012 Oct;33(20):2551-67. PubMed PMID: 22922414. Epub 2012/08/28. eng.
3.             Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Journal of the American College of Cardiology. 2000 Sep;36(3):959-69. PubMed PMID: 10987628. Epub 2000/09/15. eng.
4.             Chest Pain of Recent Onset: Assessment and Diagnosis of Recent Onset Chest Pain or Discomfort of Suspected Cardiac Origin. London: National Clinical Guideline Centre for Acute and Chronic Conditions.; 2010 Mar.
5.             Reichlin T, Schindler C, Drexler B, Twerenbold R, Reiter M, Zellweger C, et al. One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T. Archives of internal medicine. 2012 Sep 10;172(16):1211-8. PubMed PMID: 22892889. Epub 2012/08/16. eng.
6.             McCord J, Nowak RM, McCullough PA, Foreback C, Borzak S, Tokarski G, et al. Ninety-minute exclusion of acute myocardial infarction by use of quantitative point-of-care testing of myoglobin and troponin I. Circulation. 2001 Sep 25;104(13):1483-8. PubMed PMID: 11571240. Epub 2001/09/26. eng.
7.             Straface AL, Myers JH, Kirchick HJ, Blick KE. A rapid point-of-care cardiac marker testing strategy facilitates the rapid diagnosis and management of chest pain patients in the emergency department. American journal of clinical pathology. 2008 May;129(5):788-95. PubMed PMID: 18426740. Epub 2008/04/23. eng.
8.             Caragher TE, Fernandez BB, Jacobs FL, Barr LA. Evaluation of quantitative cardiac biomarker point-of-care testing in the emergency department. The Journal of emergency medicine. 2002 Jan;22(1):1-7. PubMed PMID: 11809549. Epub 2002/01/26. eng.
9.             Goodacre S, Bradburn M, Fitzgerald P, Cross E, Collinson P, Gray A, et al. The RATPAC (Randomised Assessment of Treatment using Panel Assay of Cardiac markers) trial: a randomised controlled trial of point-of-care cardiac markers in the emergency department. Health technology assessment (Winchester, England). 2011 May;15(23):iii-xi, 1-102. PubMed PMID: 21616014. Epub 2011/05/28. eng.
10.          Azzazy HM, Christenson RH. Cardiac markers of acute coronary syndromes: is there a case for point-of-care testing? Clinical biochemistry. 2002 Feb;35(1):13-27. PubMed PMID: 11937074. Epub 2002/04/09. eng.
11.          Ekelund U, Forberg JL. New methods for improved evaluation of patients with suspected acute coronary syndrome in the emergency department. Emergency medicine journal : EMJ. 2007 Dec;24(12):811-4. PubMed PMID: 18029508. Pubmed Central PMCID: PMC2658347. Epub 2007/11/22. eng.
12.          Townsend N WK, Bhatnagar P, Smolina K, Nichols M, Leal J, Luengo-Fernandez R, Rayner M. Coronary heart disease statistics 2012 edition. British Heart Foundation: London. 2012.
13.          Than M, Cullen L, Reid CM, Lim SH, Aldous S, Ardagh MW, et al. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet. 2011 Mar 26;377(9771):1077-84. PubMed PMID: 21435709. Epub 2011/03/26. eng.
14.          Aldous SJ, Richards MA, Cullen L, Troughton R, Than M. A new improved accelerated diagnostic protocol safely identifies low-risk patients with chest pain in the emergency department. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2012 May;19(5):510-6. PubMed PMID: 22594354. Epub 2012/05/19. eng.
15.          Birkhahn RH, Haines E, Wen W, Reddy L, Briggs WM, Datillo PA. Estimating the clinical impact of bringing a multimarker cardiac panel to the bedside in the ED. The American journal of emergency medicine. 2011 Mar;29(3):304-8. PubMed PMID: 20825823. Epub 2010/09/10. eng.
16.          Meek R, Braitberg G, Nicolas C, Kwok G. Effect on emergency department efficiency of an accelerated diagnostic pathway for the evaluation of chest pain. Emergency medicine Australasia : EMA. 2012 Jun;24(3):285-93. PubMed PMID: 22672169. Epub 2012/06/08. eng.
17.          Lee-Lewandrowski E, Januzzi JL, Jr., Grisson R, Mohammed AA, Lewandrowski G, Lewandrowski K. Evaluation of first-draw whole blood, point-of-care cardiac markers in the context of the universal definition of myocardial infarction: a comparison of a multimarker panel to troponin alone and to testing in the central laboratory. Archives of pathology & laboratory medicine. 2011 Apr;135(4):459-63. PubMed PMID: 21466362. Epub 2011/04/07. eng.
18.          Macdonald SP, Nagree Y. Rapid risk stratification in suspected acute coronary syndrome using serial multiple cardiac biomarkers: a pilot study. Emergency medicine Australasia : EMA. 2008 Oct;20(5):403-9. PubMed PMID: 18973637. Epub 2008/11/01. eng.
19.          Ng SM, Krishnaswamy P, Morissey R, Clopton P, Fitzgerald R, Maisel AS. Ninety-minute accelerated critical pathway for chest pain evaluation. The American journal of cardiology. 2001 Sep 15;88(6):611-7. PubMed PMID: 11564382. Epub 2001/09/21. eng.
20.          Apple FS, Christenson RH, Valdes R, Jr., Andriak AJ, Berg A, Duh SH, et al. Simultaneous rapid measurement of whole blood myoglobin, creatine kinase MB, and cardiac troponin I by the triage cardiac panel for detection of myocardial infarction. Clinical chemistry. 1999 Feb;45(2):199-205. PubMed PMID: 9931041. Epub 1999/02/04. eng.
21.          Rathore S, Knowles P, Mann AP, Dodds PA. Is it safe to discharge patients from accident and emergency using a rapid point of care Triple Cardiac Marker test to rule out acute coronary syndrome in low to intermediate risk patients presenting with chest pain? European journal of internal medicine. 2008 Nov;19(7):537-40. PubMed PMID: 19013384. Epub 2008/11/18. eng.
22.          Di Serio F, Antonelli G, Trerotoli P, Tampoia M, Matarrese A, Pansini N. Appropriateness of point-of-care testing (POCT) in an emergency department. Clinica chimica acta; international journal of clinical chemistry. 2003 Jul 15;333(2):185-9. PubMed PMID: 12849903. Epub 2003/07/10. eng.
23.          Newby LK, Storrow AB, Gibler WB, Garvey JL, Tucker JF, Kaplan AL, et al. Bedside multimarker testing for risk stratification in chest pain units: The chest pain evaluation by creatine kinase-MB, myoglobin, and troponin I (CHECKMATE) study. Circulation. 2001 Apr 10;103(14):1832-7. PubMed PMID: 11294799. Epub 2001/04/11. eng.
24.          Kratz A, Januzzi JL, Lewandrowski KB, Lee-Lewandrowski E. Positive predictive value of a point-of-care testing strategy on first-draw specimens for the emergency department-based detection of acute coronary syndromes. Archives of pathology & laboratory medicine. 2002 Dec;126(12):1487-93. PubMed PMID: 12456209. Epub 2002/11/29. eng.
25.          Hillis GS, Zhao N, Taggart P, Dalsey WC, Mangione A. Utility of cardiac troponin I, creatine kinase-MB(mass), myosin light chain 1, and myoglobin in the early in-hospital triage of "high risk" patients with chest pain. Heart (British Cardiac Society). 1999 Nov;82(5):614-20. PubMed PMID: 10525520. Pubmed Central PMCID: PMC1760765. Epub 1999/10/20. eng.
26.          Mutrie D. A new chest pain strategy in Thunder Bay. Cjem. 1999 Apr;1(1):57-61. PubMed PMID: 17659105. Epub 2007/07/31. eng.
27.          Lee-Lewandrowski E, Corboy D, Lewandrowski K, Sinclair J, McDermot S, Benzer TI. Implementation of a point-of-care satellite laboratory in the emergency department of an academic medical center. Impact on test turnaround time and patient emergency department length of stay. Archives of pathology & laboratory medicine. 2003 Apr;127(4):456-60. PubMed PMID: 12683874. Epub 2003/04/10. eng.
28.          Cullen L, Parsonage WA, Greenslade J, Lamanna A, Hammett CJ, Than M, et al. Comparison of early biomarker strategies with the Heart Foundation of Australia/Cardiac Society of Australia and New Zealand guidelines for risk stratification of emergency department patients with chest pain. Emergency medicine Australasia : EMA. 2012 Dec;24(6):595-603. PubMed PMID: 23216719. Epub 2012/12/12. eng.
29.          Leshem-Rubinow E, Abramowitz Y, Malov N, Hadad M, Tamari M, Golovner M, et al. Prehospital cardiac markers in defining ambiguous chest pain. Archives of internal medicine. 2011 Dec 12;171(22):2056-7. PubMed PMID: 22158578. Epub 2011/12/14. eng.
30.          Apple FS, Murakami MM. The diagnostic utility of cardiac biomarkers in detecting myocardial infarction. Clinical cornerstone. 2005;7 Suppl 1:S25-30. PubMed PMID: 15899366. Epub 2005/05/19. eng.
31.          Guideline for the management of patients with acute coronary syndromes without persistent ECG ST segment elevation. British Cardiac Society Guidelines and Medical Practice Committee and Royal College of Physicians Clinical Effectiveness and Evaluation Unit. Heart (British Cardiac Society). 2001 Feb;85(2):133-42. PubMed PMID: 11156660. Pubmed Central PMCID: PMC1729608. Epub 2001/01/13. eng.
32.          Aldous SJ. Cardiac biomarkers in acute myocardial infarction. International journal of cardiology. 2013 Apr 15;164(3):282-94. PubMed PMID: 22341694. Epub 2012/02/22. eng.
33.          Collinson PO, Gaze DC, Thokala P, Goodacre S. Randomised Assessment of Treatment using Panel Assay of Cardiac markers--Contemporary Biomarker Evaluation (RATPAC CBE). Health technology assessment (Winchester, England). 2013;17(15):v-vi, 1-122. PubMed PMID: 23597479. Epub 2013/04/20. eng.
34.          Apple FS, Saenger AK. The state of cardiac troponin assays: looking bright and moving in the right direction. Clinical chemistry. 2013 Jul;59(7):1014-6. PubMed PMID: 23592505. Epub 2013/04/18. eng.
35.          Collinson P, Goodacre S, Gaze D, Gray A. Very early diagnosis of chest pain by point-of-care testing: comparison of the diagnostic efficiency of a panel of cardiac biomarkers compared with troponin measurement alone in the RATPAC trial. Heart (British Cardiac Society). 2012 Feb;98(4):312-8. PubMed PMID: 22076016. Epub 2011/11/15. eng.
36.          Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--summary article: 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). Journal of the American College of Cardiology. 2002 Oct 2;40(7):1366-74. PubMed PMID: 12383588. Epub 2002/10/18. eng.
37.          Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). Journal of the American College of Cardiology. 2004 Aug 4;44(3):671-719. PubMed PMID: 15358045. Epub 2004/09/11. eng.

Appendix

  1. ESC/ACC definition of Myocardial Infarction(2): Detection of rise and/or fall of cardiac biomarker values (preferably cTn) with at least one value above 99th percentile and with at least one of the following
    1. Symptoms of ischaemia
    2. New or presumed new significant ST segment T waves changes or new LBBB
    3. Pathological Q wave on ECG
    4. Imaging evidence of new loss viable myocardium
    5. Identification of intracoronary thrombus by angiography or autopsy.

Authors: Jack O’Sullivan, Matthew Thompson, Christopher P. Price, Carl Heneghan, Annette Plüddemann
Contact details:  Dr. Annette Plüddemann; Email: dec@phc.ox.ac.uk

 

 

The horizon scanning reports summarise why the technology is important, provide an overview of the current available evidence and assess whether it could be adopted in the NHS and if so, what the requirements are for the delivery of the technology into practice.

These reports are freely accessible and disseminated to the NIHR Health Technology Assessment Programme (HTA), the National Institute for Health and Clinical Excellence (NICE) and commissioners of health care services to facilitate adoption and identify further research requirements.

Methods can be downloaded here.

We are funded by the National Institute for Health Research (NIHR) and collaborate with the Health Economics Research Centre at Oxford University.