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Critical Appraisal. DR Joshna Rajbaran. CARDIAC TROPONIN and OUTCOME in ACUTE HEART FAILURE. NEJM 358;20 MAY 15,2008. THE AIM:. To describe the association between elevated cardiac troponin levels and adverse events in hospitalized patients with ACUTE DECOMPENSATED HEART FAILURE. WHY??.

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Critical appraisal l.jpg

Critical Appraisal

DR Joshna Rajbaran



The aim l.jpg
THE AIM:

  • To describe the association between elevated cardiac troponin levels and adverse events in hospitalized patients with ACUTE DECOMPENSATED HEART FAILURE


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WHY??

  • Because an objective risk-stratification process for the evaluation of acute decompensated heart failure is lacking.


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NB: Troponins presents with acute decompensated heart failure remains uncertain.

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!!


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THE KEY DIFFERENCES presents with acute decompensated heart failure remains uncertain.

  • LARGE STUDY

  • SHORT TERM OUTCOMES

  • IN HOSPITALIZED PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE.


Method l.jpg
METHOD presents with acute decompensated heart failure remains uncertain.

  • Registry data:

    • ADHERE( Acute Decompensated Heart Failure National Registry)

    • Observational registry

    • 274 hospitals

    • TIME FRAME :October 2001 January 2004


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  • Inclusion criteria: presents with acute decompensated heart failure remains uncertain.

    Hospitalization & documentation of the measurement of trop I or trop T at “INITIAL” evaluation


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  • Exclusion criteria: presents with acute decompensated heart failure remains uncertain.

    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!!!


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METHOD presents with acute decompensated heart failure remains uncertain.

  • 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


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Method presents with acute decompensated heart failure remains uncertain.

  • 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


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  • Statistical analysis ( cont) presents with acute decompensated heart failure remains uncertain.

  • Associations between therapy & mortality

  • Controls used in this regard

  • Mortality was adjusted for relevant prognostic factors


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  • Logistic regression adjusted for: presents with acute decompensated heart failure remains uncertain.

    age / blood urea nitrogen / SBP /

    DBP / serum creatinine / serum sodium / HR /dyspnea at rest

  • 1.2% records excluded due to missing values


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  • SAS software presents with acute decompensated heart failure remains uncertain.

  • Study designed by all authors

  • ADHERE statisticians


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METHOD presents with acute decompensated heart failure remains uncertain.

  • Source

  • Time period

  • Inclusion criteria

  • Exclusion criteria

  • IHD/Race / Gender

  • troponin measurements justified

  • Statistical analysis explained

  • Tools and teams stated


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RESULTS presents with acute decompensated heart failure remains uncertain.

  • Troponin levels & characterists of the patients


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105,388 84,872 ( 80.5% ) presents with acute decompensated heart failure remains uncertain.

Hospitalized Trop tested

Cr < 2mg/dl

67,924

Positive Negative

4240 (6,2%) 63,684



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  • Troponin- positive patients on admission: cohorts!!!

  • 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!!


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REVISION OF TERMINOLOGY cohorts!!!

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!!


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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.


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RESULTS who are correctly identified by the test.

  • 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)


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RESULTS was it predictive of mortality.

  • 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


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RESULTS was it predictive of mortality.

  • 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


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Main findings and their value: was it predictive of mortality.

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


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  • Value of findings from Trop negative cohort was it predictive of mortality.

    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


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  • Studies correlating Troponin with physiological variables was it predictive of mortality.

  • 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!!!


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  • Suggested guideline!!! was it predictive of mortality.

  • 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!!!!


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LIMITATIONS was it predictive of mortality.

  • 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


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Critical appraisal was it predictive of mortality.

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


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With relevance to SA was it predictive of mortality.

  • 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.


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  • 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!!


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  • 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.


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