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1. Critical Appraisal DR Joshna Rajbaran
2. CARDIAC TROPONIN and OUTCOME in ACUTE HEART FAILURE NEJM 358;20 MAY 15,2008
3. THE AIM: To describe the association between elevated cardiac troponin levels and adverse events in hospitalized patients with ACUTE DECOMPENSATED HEART FAILURE
4. WHY?? Because an objective risk-stratification process for the evaluation of acute decompensated heart failure is lacking.
5. The value of measuring serum cardiac troponin when a patient presents with acute decompensated heart failure remains uncertain.
6. NB: Troponins Trop T & Trop I are regulatory proteins with a very high specificity for cardiac injury . They are released early ( 2-4 hrs) & can persist for up to 7 days.
Troponin testing is primarily used as a tool in diagnosing myocardial infarctions.
Elevated levels suggest myocardial or some form of cardiac damage.
Insignificant if used in the absence of S&S of cardiac disease!!
7. THE KEY DIFFERENCES LARGE STUDY
SHORT TERM OUTCOMES
IN HOSPITALIZED PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE.
8. METHOD Registry data:
ADHERE( Acute Decompensated Heart Failure National Registry)
TIME FRAME :October 2001 ?January 2004
9. Inclusion criteria:
Hospitalization & documentation of the measurement of trop I or trop T at “INITIAL” evaluation
10. Exclusion criteria:
serum creatinine level>2.0mg/dl
Ischemic heart failure defined as cause if :
hx coronary artery disease OR
hx myocardial infarction
Not as exclusion criteria!!!
11. METHOD Troponin measurement:
Trop T & trop I were interchangeable levels considered positive, with cut-off based on expert consensus!!
Trop T=0.1µg/l & Trop I =1.0µg/l
12. Method Statistical analysis:
Primary out-come all causes
Secondary out-come differences in medical mx / procedures / length of stay between +ve & -ve cohorts
All outcomes were specified before the data were examined
13. Statistical analysis ( cont)
Associations between therapy & mortality
Controls used in this regard
Mortality was adjusted for relevant prognostic factors
14. Logistic regression adjusted for:
age / blood urea nitrogen / SBP /
DBP / serum creatinine / serum sodium / HR /dyspnea at rest
1.2% records excluded due to missing values
15. SAS software
Study designed by all authors
IHD/Race / Gender
troponin measurements justified
Statistical analysis explained
Tools and teams stated
17. RESULTS Troponin levels & characterists of the patients
18. 105,388 84,872 ( 80.5% )
Hospitalized Trop tested
Cr < 2mg/dl
4240 (6,2%) 63,684
19. There were small but significant differences between the two cohorts!!!
20. Troponin- positive patients on admission:
Less likely AF
Summary of characteristics given +ve vs –ve Trop
No comparison made for the two proteins as only 2% had both tested!!
21. REVISION OF TERMINOLOGY Odds ratio :provides a more useful way of presenting diagnostic data & can be applied to individual patients in a way that specificity & sensitivity cannot . It is a number btw 0 to infinity IF > 1 indicates that the information increases the likelihood of the suspected diagnoses. IF <1 it decreases the likelihood of the suspected diagnoses!!
22. SPECIFICITY: the proportion of patients WITHOUT the disease who are correctly identified by the test.
SENSITIVITY: the proportion of patients WITH the disease who are correctly identified by the test.
23. RESULTS In-hospital mortality
Trop Positive (8.0%) > Trop Negative (2.7%) patients.......... (P<0.001)
Trop as a continuous variable
Adjusted odds ratio for death (P<0.001)
24. IHF was not a useful discriminator of Troponin status, nor was it predictive of mortality.
IHF Trop +ve 53% Trop –ve 52%
Trop +ve mortality 8,4% IHF
Trop –ve mortality 2,8% IHF
25. RESULTS Treatment , Troponin status & Mortality
+ve more likely to receive: nitroglycerine , inotropes & vasodilators
Resource utilization and mortality
No interaction between treatment & Troponin status with respect to mortality
26. RESULTS Sample size large but justified
Basic data adequately described
Variables taken into account
Missing data accounted for
Numbers add up
High risk cohort established
Statistical significance assessed
27. Main findings and their value: Prognostic value / cost
Early assessment of risk/ triage & management
Add to existing risk-stratification data for predicting the short term risk of death among patients with acute decompensated heart failure... Blood urea>15.4mmol/l
SBP < 115mm Hg
More aggressive therapeutic approach justified
28. Value of findings from Trop negative cohort
Identifying low risk patients/ planning Rx
Other studies ?the impact of early risk stratification has been supported
SMALLER STUDIES-98 CONSECUTIVE PTS
29. Studies correlating Troponin with physiological variables
Impact on guidelines :
National-ACS Trop & brain natriuretic peptide or N- terminal pro-brain peptide.
Current for Heart Failure Trop NOT mentioned & brain nitriuretic peptide only if dx uncertain!!!
30. Suggested guideline!!!
Measurement of Troponin levels in patients who present with heart failure provides independent prognostic information regarding in hospital death & other clinical outcomes & can be useful for risk stratification of such patients!!!!
31. LIMITATIONS Retrospective analysis
ADHERE large data set : investigator discretion , diagnosis not objectively ascertained , cause of death not consistently recorded
Introduction of variability/ bias
Measurement only at admission
Interaction with other biomarkers
Under represented adverse outcomes
32. Critical appraisal INFORMATIVE STUDY
STRENGTHS & LIMITATIONS WITH SUGGESTIONS OFFERED
I FOUND NO REASON TO QUESTION THE STATISTICAL APPROACH
SUGGESTIONS FOR FUTURE STUDIES
OTHER RELEVANT STUDIES DOCUMENTED
33. With relevance to SA South African statistics :10 473 mortalities per annum d/t Heart Failure vs. US 55,704
Further evaluation of other biomarkers vs Trop T required
Cost factors need to be examined
Ischaemic heart disease is the commonest cause for acute heart failure in America.
34. HOWEVER, in Sub- Saharan Africa the causes in Africans are largely ( > 90%) NON-ISCHAEMIC viz.:
HPT / cardiomyopathy / Rheumatic heart disease / chronic lung disease / pericardial disease
Coronary artery disease and it’s complications remain uncommon in Africa but the situation is changing!!
35. I found the journal article rather transparent in it’s limitations
However, there was one limitation that seemed to stand out:
that some patients with both heart failure and ACS may have been included!!!!
I think that with urbanization ,varying risk profiles amongst race groups , risk prone behaviour & diet, that the findings are worthy of consideration in our setting.
36. Finally , EARLY RISK STRATIFICATION may help identify patients who are likely to receive the greatest benefit from intensive therapy.....that in itself highlights it’s relevance to emergency medicine!!!!