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Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures
Published on: March 12, 2018
Methods of creatine kinase-MB analysis to predict mortality in patients with myocardial infarction treated with
Renato D Lopes1, Yuliya Lokhnygina, Victor Hasselblad
1Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt Street, Room 0311, Terrace Level, Box 3850, Durham, NC 27705, USA. renato.lopes@duke.edu
Insights
Larger infarct size in ST-segment elevation myocardial infarction (STEMI) correlates with higher mortality. Advanced curve modeling offers similar insights to traditional creatine kinase (CK)-MB measurements for quantifying infarct size.
Area of Science:
- Cardiology
- Biomedical Engineering
Background:
- Creatine kinase (CK)-MB release quantifies infarct size, a key predictor of mortality in ST-segment elevation myocardial infarction (STEMI).
- Traditional methods for infarct size quantification include peak CK-MB and area under the curve (AUC).
- Evaluating alternative CK-MB measurement approaches is crucial for refining prognostic assessments in STEMI.
Purpose of the Study:
- To assess novel curve-fitting techniques for quantifying infarct size in STEMI patients.
- To compare the prognostic value of these advanced methods against traditional CK-MB measurements.
- To investigate the relationship between infarct size and clinical outcomes, including mortality and a composite of adverse events.
Main Methods:
- Utilized data from 1,718 STEMI patients from the COMMA and COMPLY trials, treated with either percutaneous coronary intervention or fibrinolysis.
- Employed curve-fitting techniques to calculate CK-MB AUC and estimate peak CK-MB, alongside traditional methods.
- Applied Cox proportional hazards modeling to analyze associations between infarct size metrics and 90-day mortality and a composite outcome.
Main Results:
- All CK-MB measurement methods, including curve-fitting, showed significant associations with higher mortality in the fibrinolytic-treated (COMPLY) group.
- Associations were similar but not statistically significant in the PCI-treated (COMMA) group.
- All CK-MB measures were significantly associated with the composite outcome of death, heart failure, shock, and stroke at 90 days in both trials.
Conclusions:
- Sophisticated curve modeling provides infarct-size information comparable to traditional methods in STEMI patients.
- Further research is needed to validate these findings in non-STEMI populations and with varied data collection frequencies.
- The study highlights the consistent prognostic importance of infarct size across different measurement techniques.
Background:
Larger infarct size measured by creatine kinase (CK)-MB release is associated with higher mortality and has been used as an important surrogate endpoint in the evaluation of new treatments for ST-segment elevation myocardial infarction (STEMI). Traditional approaches to quantify infarct size include the observed CK-MB peak and calculated CK-MB area under the curve (AUC). We evaluated alternative approaches to quantifying infarct size using CK-MB values, and the relationship between infarct size and clinical outcomes.
Methods:
Of 1,850 STEMI patients treated with reperfusion therapy in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) (percutaneous coronary intervention (PCI)-treated) and the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) (fibrinolytic-treated) trials, 1,718 (92.9%) (COMMA, n = 868; COMPLY, n = 850) had at least five of nine protocol-required CK-MB measures. In addition to traditional methods, curve-fitting techniques were used to determine CK-MB AUC and estimated peak CK-MB. Cox proportional hazards modeling assessed the univariable associations between infarct size and mortality, and the composite of death, heart failure, shock and stroke at 90 days.
Results:
In COMPLY, CK-MB measures by all methods were significantly associated with higher mortality (hazard ratio range per 1,000 units increase: 1.09 to 1.13; hazard ratio range per 1 standard deviation increase: 1.41 to 1.62; P <0.01 for all analyses). In COMMA, the associations were similar but did not reach statistical significance. For the composite outcome of 90-day death, heart failure, shock and stroke, the associations with all CK-MB measures were statistically significant in both the COMMA and COMPLY trials.
Conclusions:
Sophisticated curve modeling is an alternative to infarct-size quantification in STEMI patients, but it provides information similar to that of more traditional methods. Future studies will determine whether the same conclusion applies in circumstances other than STEMI, or to studies with different frequencies and patterns of CK-MB data collection.
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