Phác đồ 1 giờ trong chẩn đoán và điều trị nhồi máu cơ tim cấp

Phác Đồ 1 Giờ Chẩn Đoán Và Loại Trừ Nhồi Máu Cơ
Tim Cấp Với Troponin T Siêu Nhạy
The one-hour algorithm to rule-out and rule-in of Acute Myocardial Infarction with
cardiac Troponin T-high sensitive
PGS TS Trần Văn Huy FACC FESC
Phó Chủ Tịch Phân Hội THA VN,
Trưởng Khoa TM BV Tỉnh Khánh Hòa
Giảng Viên Thỉnh Giảng ĐHYD Huế, ĐHTN

Test early.
Treat right.
Save lives.


Có gì mới nổi bật trong khuyến cáo về chẩn đoán NMCT cấp
2015?
Khuyến Cáo ESC 9/2015 NSTEAMI

Initial assessment of patients with suspected acute coronary syndromes.
ESC GUIDELINES NSTAMI European Heart Journal Advance Access published August 29, 2015


Khuyến cáo ESC 2015 về chẩn đoán, phân tầng nguy cơ và vai trò
troponin ở bệnh nhân nghi ngờ hội chứng mạch vành ST không chênh
Recommendations

Class

Level Ref.c

It is recommended to base diagnosis and initial short-term ischaemic

and bleeding risk stratification on a combination of clinical history,
symptoms, vital signs, other physical findings, ECG and laboratory
results.

I

A

28,109–112

A rapid rule-out and rule-in protocol at 0 h and 1 h is
recommended if a high-sensitivity cardiac troponin test with a
validated 0 h/1 h algorithm is available. Additional testing after
3–6 h is indicated if the first two troponin measurements are not
conclusive and the clinical condition is still suggestive of ACS.

I

B

30–34, 36,
39,
51–55

It is recommended to use established risk scores for prognosis
estimation

I

B

84,94,106

Diagnosis and risk stratification

ESC GUIDELINES NSTAMI European Heart Journal Advance Access published August 29, 2015


0 h/3 h rule-out algorithm of non-ST-elevation acute coronary
syndromes using high-sensitivity cardiac troponin assays

ESC GUIDELINES NSTAMI European Heart Journal Advance Access published August 29, 2015


Phác đồ rule-in và rule out 0 h/1 h bằng hs-cTn ở bệnh nhân nghi
ngờ NMCT không ST chênh lên (NSTEMI)

ESC GUIDELINES NSTAMI European Heart Journal Advance Access published August 29, 2015


Chứng cứ nào cho phác đồ 0-1h hs cTn?
14 nghiên cứu về phác đồ 0-1h, trong đó hs cTnT 10/14
• APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation ) 2012
• TRAPID-AMI (High sensitivity cardiac Troponin T assay for RAPID rule-out of
Acute Myocardial Infarction) is a Roche-sponsored clinical trial presented at the
meeting ESC 2014
• APACE : 2015. The “APACE revalidation” study.(Prospective validation of a 1-hour
algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity
cardiac troponin T assay)
Reichlin T. et al., CMAJ. 2015, April

• 1-h algorithm for hs-cTnI
Rubini Gimenez M. et al., Am J Med 2015, Mar 31


Acute myocardial infarction (AMI)

Time is life

Each year over
7 million people have an AMI
worldwide1

AMI is a life-threatening
condition

STEMI mortality:
(1 year)

This is a race against the clock where every minute
counts

≈9%

NSTEMI mortality: ≈ 11.6 %
(1 year)

1.
2.

Every 30 minutes of delay between symptoms and

treatment increases the relative risk of 1-year
mortality by 7.5% in patients with AMI2

White and Chew (2008). Lancet 372:570-584.
De Luca et al (2004). Circulation 109:1223-1225.


Time is life

Is a safe AMI diagnosis possible in a shorter time?
• Serial blood samples at variable time intervals are required for the diagnosis of AMI and to
differentiate acute from chronic cardiac disease1
• 2011 ESC guidelines recommend, in conjunction with full clinical assessment including
12–lead ECG, either a 6-9 hours observation time with conventional cTn tests or 3 hours ruleout protocol using high sensitivity Troponin1
Conventional troponin tests 1
High sensitivity troponin tests1

0
1.

2.

2.

1.

Faster rule-in
Faster rule-out

Reduce time to diagnosis

Possible ?

1
Hamm et al (2011). Eur Heart J 32:2999–3054.

3
Time since admission (hours)

Faster appropriate therapy
Reduced ED crowding

2.

6
cTn: Cardiac troponin; ECG: Electrocardiogram;
ED: Emergency department;
ESC: European Society of Cardiology


Phác đồ 0-1h cTnT chẩn đoán & loại trừ NMCTC
The APACE study: a 1-hour cTnT-hs algorithm
Advantageous Predictors of Acute Coronary Syndrome Evaluation
 A pilot study with 436 patients presenting at the ED <12 h from chest pain onset1
 Algorithm based on cTnT-hs baseline value and absolute change within the first hour (∆1 h)1
cTnT-hs values in patients presenting
to the ED with chest pain

Proposed algorithm

0 h <12 ng/L and
∆1 h <3 ng/L

Others

0 h ≥52 ng/L or
∆1 h ≥5 ng/L

Rule-out

Observational zone

Rule-in

1. Reichlin et al (2012). Arch Intern Med 172:1211-1218.

0 h: Presentation to the ED; ∆1 h: Absolute change of cTnT-hs within the first
hour; AMI: Acute myocardial infarction; cTnT-hs: Cardiac Troponin T high-sensitive;
ED: Emergency department; NPV: Negative predictive value; PPV: Positive predictive
value


The APACE study: Algorithm and results
cTnT-hs values in patients presenting
to the ED with chest pain

Proposed algorithm

Results

0 h <12 ng/L and
∆1 h <3 ng/L

Others

0 h ≥52 ng/L or
∆1 h ≥5 ng/L

Rule-out

Observational zone

Rule-in

60% of patients
(n = 259)
Sensitivity: 100%
NPV: 100%

23% of patients
(n = 101)
Prevalence of AMI: 8%

17% of patients
(n = 76)
Specificity: 97%
PPV: 84%

• Definitive rule-in or rule-out of a total of 77 % of patients within 1 hour 1
• Very high NPV for a safe rule-out of 60 % patients in 1 hour1

1. Reichlin et al (2012). Arch Intern Med 172:1211-1218.

0 h: Presentation to the ED; ∆1 h: Absolute change of cTnT-hs within the first
hour; AMI: Acute myocardial infarction; cTnT-hs: Cardiac Troponin T high-sensitive;
ED: Emergency department; NPV: Negative predictive value; PPV: Positive predictive
value


Low mortality in patients ruled-out for AMI
APACE 2012 results*
Survival at 30 days (A) and 24 months (B) according to cTnT-hs algorithm category
B

100

99.8%

98
Survival (%)

100

95

96
95.3%

94

Observational

zone (n=212)

90

p<0.001
0

10

20

85.4%

p<0.001

80
30

Rule-in
(n=169)

89.1%

85

92
90

Rule-out
(n=491)

98.1%

98.6%

Survival (%)

A

0

Time (days)

Reichlin T. et al., Arch Int Med 2012;
172(16):1211-8

6

12
Time (months)

18

24


Multicenter evaluation of a 1h-algorithm in the diagnosis of myocardial infarction
using high-sensitivity cardiac Troponin T
Christian Mueller, Evangelos Giannitsis, Michael Christ, Jorge Ordóñez-Llanos, Christopher R. deFilippi, James K. McCord, Richard Body,
Mauro Panteghini, Tomas Jernberg, Mario Plebani, Franck Verschuren, John K. French, Robert H. Christenson, Silvia Weiser, Garnet

Bendig, Peter Dilba, Bertil Lindahl,
for the TRAPID-AMI Investigators
High sensitivity cardiac Troponin T assay for RAPID rule-out of Acute Myocardial Infarction

Sponsored by
Slide presented by Prof. Mueller at the ESC 2014. />

Results
cTnT-hs values in1282 patients with chest pain <6h from 3
continents and 9 countries

95% CI 98.2-99.7%

95% CI 70.4-83.0%
Slide presented by Prof. Mueller at the ESC 2014. />

Results

0.1%

Slide presented by Prof. Mueller at the ESC 2014. />

The “APACE revalidation” study 2015: Safe and effective AMI rule-in and rule-

out in 1 hour. Reichlin T. et al., CMAJ. 2015, April

Aim
To prospectively validate the cTnT-hs 1-h algorithm in the same APACE study (2006-2009), but
recruiting new patients (2009-2013)
Study population

1714 patients with chest pain with onset/peak within 12 h of ED presentation from APACE 6 centres in
3 countries (CH, Italy, Spain)

Final study population: 1320 patients with presentation and 1-hour cTnT-hs values

Reichlin T. et al., CMAJ. 2015,


The “APACE revalidation” study (2015)
Results

Performance of the high-sensitivity cardiac troponin T (cTnT) 1-hour algorithm for rapid diagnosis of acute myocardial
infarction (MI).
CMAJ, May 19, 2015, 187(8)


Kaplan–Meier curves showing cumulative mortality within 30 days (A) and 2
years (B) of follow-up according to the classification into “rule-out” (n = 786),
“observational zone” (n = 318) and “rule-in” (n = 216) as determined by the
high-sensitivity cardiac troponin T 1-hour algorithm

CMAJ, May 19, 2015, 187(8)


Kết Luận Nghiên Cứu “APACE 2015”
• Chiến lược sử dụng những giá trị nền và những thav đổi tuyệt đối
của hs cTnT trong vòng 1 giờ để chẩn đoán những bệnh nhân
nghi ngờ NMCT đã cho thấy an toàn loại trừ cũng như chẩn đoán
chính xác NMCT cấp 3 trong 4 bệnh nhân.
• Tỷ lệ tử vong 30 ngày ở bệnh nhân loại trừ là 0% trong phác đồ

hs cTnT 1 giờ
,

Reichlin T. et al., CMAJ. 2015,
April, 187 (8)


Tóm lược chứng cứ phác đồ hs cTnT chẩn đoán nhanh NMCT cấp
Giá trị cTnT-hs 0-1h trong đau ngực cấp tại phòng cấp cứu
Giá trị phác đồ 1h
cTnT-hs ở
3038 bênh nhân
APACE-2012*,
APACE -2015**
TRAPI-AMI
2014***

0 h <12 ng/L và
∆1 h <3 ng/L

Khác

0 h ≥52 ng/L hoặc
∆1 h ≥5 ng/L

Rule out

Vùng quan sát

Rule in

60% -63.4%
NPV: 99.1-100%

22.2- 24%
Tần suất NMCTC 8-22%

14.4 -17%
PPV: 77.2 -84%

76-78% rule in - rule out NMCTC
NPV: giá trị dự đoán âm., PPV: giá trị dự đoán dương
* Reichlin et al (2012). Arch Intern Med 172:1211-1218; ** Reichlin T. et al., CMAJ. 2015, April, 187 (8)
*** Mueller et al: />

Benefit 1: Medical value for patients

Time is Life

 APACE 2012- 2015, TRAPID-AMI cTnT-hs 1 h algorithm is faster than the 3–6 h proposed by 2011
guidelines1
 Every 30 minutes of delay between symptoms and treatment increases the relative risk of 1-year mortality
by 7.5% in patients with AMI2
 Faster time to diagnosis likely to reduce patient’s anxiety
3 h saving time:
Estimated reduction in1 year mortality2 ≈ 45%

with
cTnT-hs

1.

0
1.
2.

Conventional troponin test1

High sensitivity troponin test 1

APACE 2012-2015
2.

Reduce time to diagnosis

1
Hamm et al (2011). Eur Heart J 32:2999–3054.
De Luca et al (2004). Circulation 109:1223-1225.

2.

Faster rule-in
Faster rule-out

3
Time since admission (hours)

Faster appropriate therapy
Reduced ED crowding

2.

6
cTn: Cardiac troponin; ECG: Electrocardiogram;
ED: Emergency department;
ESC: European Society of Cardiology


Benefit 2: Medical value for physicians

Time is Myocardium

Used in conjunction with ECG & other clinical information

 APACE 2012-2015, TRAPID-AMI with cTnT-hs will allow:

 rapid rule-out with safety and peace of mind in decision to discharge patients
 rapid rule-in for faster initiation of the appropriate therapy

«The beauty of the 1 hour algorithm is that we can accelerate our diagnostic procedure»

APACE 2012-15
with
cTnT-hs

1.

0
1.

Conventional troponin test1

High sensitivity troponin test 1

2.

Reduce time to diagnosis

1
Hamm et al (2011). Eur Heart J 32:2999–3054.

2.

Faster rule-in
Faster rule-out

3
Time since admission (hours)

Faster appropriate therapy
Reduced ED crowding

2.

6
cTn: Cardiac troponin; ECG: Electrocardiogram;
ED: Emergency department;
ESC: European Society of Cardiology

Benefit 3: Medical value for healthcare system

Time is Money

 Faster diagnosis with the application of APACE, TRAPID-AMI algorithm will:
 reduce the need for extended observation or repeated testing
 optimize resources saves cost for hospital stay

“This is a critical help in the allocation of resources in the ED”

APACE 2012-15
with
cTnT-hs

1.

0
1.

Conventional troponin test1

High sensitivity troponin test 1

2.

Reduce time to diagnosis

1
Hamm et al (2011). Eur Heart J 32:2999–3054.

2.

Faster rule-in
Faster rule-out

3
Time since admission (hours)

Faster appropriate therapy
Reduced ED crowding

2.

6
cTn: Cardiac troponin; ECG: Electrocardiogram;
ED: Emergency department;
ESC: European Society of Cardiology


Còn vai trò của hs cTnI như thế nào trong phác đồ 1h ?
1-h algorithm for hs-cTnI (Abbott)
One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I
Aim:
• To derive a 1h-algorithm for early rule-out and rule-in of AMI in APACE
similar to cTnT-hs using hs-cTnI from Abbott.
Study population
 Patients with chest pain with onset/peak within 12 h of ED presentation from APACE (9 centres in 3 countries) (Switzerland,
Spain, Italy)
 Final study population: 1811 patients with presentation and 1 hour- hs-cTnI-hs values
Methods

• Algorithm: Derivation cohort (n= 906), Validation cohort (n= 905)

Rubini Gimenez M. et al., Am J Med 2015,


1-h algorithm for hs-cTnI (Abbott): Results

Rubini Gimenez et al American J Medicine, Vol 128, No 8, August 2015


0-1h hs TNT : Key messages

Safe and effective AMI rule-in and rule-out in 1 hour
cTnT-hs

99.1-100%NPV

n>3’000

cTnT-hs

APACE
APACE re-validation
TRAPID-AMI

Roche cTnT-hs validates the
use of hs-cTn with a
recommended delta change

76-78%

cTnT-hs

diagnosed in
1 hour

Three studies use Roche’s
cTnT-hs 1-hour algorithm
(n>3’000) and Roche cTnT-hs

cTnT-hs 1-h performs well
for early AMI rule-out and
rule-in
and reduces diagnosis time to
1h in 76-78% of acute chest
pain patients

1h

30 day mortality
Algorithm safety confirmed
by 30d-mortality of the
patients rule-out (0.1%) and
high NPV (>99.1-100%)

More patients
More rule-in/out
Only 1 publication with
Abbott’s hs–TnI 1-h algorithm
Results suggest that

performance of is better for
Roche’s cTnT-hs