Critical Appraisal

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) • Observational registry • 274 hospitals • 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 or 176.8umol/l • 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 • ADHERE statisticians

16. METHOD • Source • Time period • Inclusion criteria • Exclusion criteria • 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 67,924 Positive Negative 4240 (6,2%) 63,684

19. There were small but significant differences between the two cohorts!!!

20. Troponin- positive patients on admission: • Lower SBP • Lower EF • 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) • Actuarial analysis • 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 7,4% non-IHF • Trop –ve mortality 2,8% IHF 2,6% non-IHF

25. RESULTS • Treatment , Troponin status & Mortality • Diuretics • +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 Cr >243.1µmol/l 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 BASEL TRIAL EFFECT STUDY SMALLER STUDIES-98 CONSECUTIVE PTS -159 PTS -RITZ-4 STUDY

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 • Troponin tests • Introduction of variability/ bias • Measurement only at admission • Interaction with other biomarkers • Under represented adverse outcomes

32. Critical appraisal INFORMATIVE STUDY AIM/METHOD/FINDINGS SIGNIFICANCE 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!!!!