Impact of Serial Troponin Release on Outcomes in Patients With Acute Heart Failure: Analysis From the PROTECT Pilot Study

Study Questions:

What is the incidence of cardiac troponin T (cTnT) elevation, and what is its clinical significance in heart failure (HF)?

Methods:

This was a secondary analysis from the PROTECT study, a multicenter pilot study assessing the impact of the adenosine receptor antagonist rolofylline in patients admitted with acute heart failure. Patients had cTnT levels measured at enrollment and days 2, 3, 4, and 7. Patients were classified as negative (≤0.01 ng/ml), detectable (>0.01 ng/ml), and positive (>0.03 ng/ml) at baseline and again at day 7. Outcomes were categorized as HF success (improvement in dyspnea), failure (death, worsening HF, early HF readmission, or persistent renal impairment), or unchanged status at day 7 and compared based on cTnT classification. A composite outcome of cardiovascular/renal rehospitalization or death by 60 days was a secondary outcome.

Results:

At baseline, the median [25th, 75th percentile] patient (n = 288) age was 73 [65, 78], 59% were male, and 74% had ischemic heart disease. Mean creatinine clearance (CrCl) was 1.53 ± 0.66 mg/dl (CrCl 57 ml/min) and 81% were either New York Heart Association class III or IV. cTnT was “detectable” in 60% (n = 172) at baseline and 34% (n = 97) had a “positive” level. At day 7, 68% of the sample had a detectable cTnT, and only 32% remained negative. Compared with negative cTnT patients, those with either a “positive” (hazard ratio [HR], 1.96; 95% confidence interval [CI], 0.71-5.5) or a “detectable” (HR, 2.6; 95% CI, 0.84-8.2) cTnT at baseline were not significantly more likely to be treatment failures. However, patients with a detectable level at either baseline or on day 7 were more likely to be treatment failures and were more likely to have an event at day 60 (HR, 1.8; 95% CI, 1.0-3.3). Kaplan-Meier survival curves demonstrated worse outcome in those with early or late cTnT elevation.

Conclusions:

The authors concluded that elevated cTnT levels were associated with worse outcomes in patients with HF.

Perspective:

Given the prevalence of HF, prognosticating outcomes and risk stratifying patients is of clinical utility. In this secondary analysis, cTnT elevation at day 7 was associated with worse outcome following HF admission. This study, however, is compromised by lack of power. Nonsignificant trends of clinically important magnitude were noted, but confidence intervals were large. Furthermore, the positive predictive value and negative predictive value (or area under a curve) of the test for predicting HF outcomes are unknown.

Clinical Topics: Heart Failure and Cardiomyopathies, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Treatment Failure, Receptors, Purinergic P1, Coronary Artery Disease, Myocardial Ischemia, Troponin T, Creatinine, Dyspnea, New York, Heart Diseases, Prognosis, Incidence, Renal Insufficiency, Cytoskeletal Proteins, Biological Markers, Troponin I, Heart Failure, Xanthines, Receptor, Adenosine A1


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