Data processing: measuring – calibrating – or testing – Measurement system in a specific environment – Biological or biochemical
Reexamination Certificate
2000-08-21
2003-12-09
Marschel, Ardin H. (Department: 1631)
Data processing: measuring, calibrating, or testing
Measurement system in a specific environment
Biological or biochemical
C435S004000, C435S015000, C703S011000
Reexamination Certificate
active
06662114
ABSTRACT:
FIELD OF THE INVENTION
The present invention concerns methods of predicting clinical outcomes such as likelihood of mortality or death, new congestive heart failure, new pulmonary congestion or the like in a patient that has received reperfusion therapy such as thrombolytic therapy.
BACKGROUND OF THE INVENTION
Myocytes contain high intracellular concentrations of biochemical markers that are released into circulation after cell death. Using mathematical functions to model the release of these markers after myocardial infarction (MI) has been under investigation since the early 1970s (S. Witteveen et al., In: Haas J H, Hemker H C, Snellen H A, eds. Ischemic Heart Disease. Baltimore: Williams & Wilkins, 36 (1970); W. Shell et al.,
J Clin. Invest
. 50: 2614 (1971); B. Sobel et al.,
Circulation
46: 640 (1972); R. Roberts et al.,
Circulation
52: 743 (1975); S. Witteveen et al.,
Br Heart J
37:795-(1975); R. Norris et al.,
Circulation
51: 614 (1975); W. Ryan et al.,
Am Heart J
101: 162 (1981); P. Grande et al.,
Circulation
65:756 (1982); L. Ong et al.,
Am J Cardiol
64:11 (1989); W. Hermens et al.,
Circulation
81:649 (1990); H. Schwerdt et al.,
Cardiovasc Res
24:328 (1990)). However, many models have been criticized, because the calculated quantity of biochemical markers released from the intracellular compartment often did not accurately relate to infarct size, commonly expressed in grams of infarcted tissue, in dogs with induced coronary occlusion (C. Roe and C. Starmer,
Circulation
52:1 (1975); C. Roe et al.,
Circulation
55:438 (1977); C. Roe,
Clin Chem
23:1807 (1977); Horder et al.,
Scand J Clin Lab Invest
41:41 (1981); R. Roberts,
Circulation
81:707 (1990)). This discordance may have resulted from an incomplete understanding of the complex mechanisms governing the clearance kinetics of biochemical markers after MI. Also, the effects of infarct extension (F. Cobb et al.,
Circulation
60:145 (1979)) and reperfusion (J. Jarmakani et al.,
Cardiovasc Res
10:245 (1976); S. Vatner et al.,
J Clin Invest
61:1048 (1978)) were not accounted for in these methods. Multicompartment models have been used in an attempt to relate empirical observations with the physiological processes of marker release and clearance. Better recovery in terms of grams of infarcted tissue has been reported with use of a two-compartment model for lactate dehydrogenase and creatine kinase (CK) release in permanently occluded canine models.
Although of scientific interest physiologically, calculating the precise amount of biochemical marker released after necrosis may not reflect the primary clinical objective. Additionally, most methods use permanent occlusion models for development; these physiologically-based models may not be appropriate in the thrombolytic era, where the benefit of establishing coronary artery patency has been shown (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI),
Lancet
1:397-402 (1986); R. Wilcox et al.,
Lancet
2:525 (1988)(ASSET); ISIS-2 Collaborative Group, Lancet 2:349 (1988); the TIMI Study Group,
N Engl J Med
312:932 (1985); The GUSTO Investigators,
N Engl J Med
329: 673 (1993); A. Tiefenbrunn and B. Sobel,
Fibrinolysis
3:1 (1989)).
In view of the foregoing, there is a need for new ways to predict clinical outcome for a patient after thrombolytic therapy.
SUMMARY OF THE INVENTION
A first aspect of the present invention is a method for predicting the clinical outcome for a patient after said patient has received therapy for acute coronary syndromes such as myocardial infarction. The method comprises:
(a) optionally, but preferably, detecting a first variable comprising a serum creatine kinase-MB release curve area in said patient after initiation of therapy;
(b) optionally, but preferably, detecting a second variable comprising a serum creatine kinase-MB release curve maxima in said patient after initiation of therapy; and then
(c) optionally, but preferably, detecting a third variable comprising the slope of the descending portion of the serum creatine kinase-MB release curve after initiation of therapy (wherein a steep slope for said descending portion is a more favorable indicator of clinical outcome than a shallow slope); and
(d) generating a prediction of clinical outcome for said patient from the variables collected above. While the variables noted above are indicated to be optional, it will be appreciated that at least one of the first through third variables must actually be detected and used in the generating step. Preferably at least one of either the second or third variables is actually detected and used in the generating step.
The foregoing and other objects and aspects of the present invention are explained in detail below.
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Carrier et al., Cardiac Troponin T and Creatine Kinase MB Isenzyme as Biocehmical Markers . . . , 1994, The Journal of Heart and Lung Transplantation, vol. 13, No. 4, pp. 696-700.*
Dissmann et al., Estimation of enzymatic infarct size: Direct comparison of the marker enzymes creatine kinaws and x-hydroxybutyrate dehydrogenase, 1998, American Heart Journal, vol. 135, No. 1, pp. 1-9.*
Cobb et al.,Effect of Extension of Infarction on Serial CK Activity, Circulation 60:145-154 (1979).
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Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI),Effectiveness of Intravenous Thrombolytic Treatment in Acute Myocardial Infarction, Lancet 1:397-402 (1986).
Hermens et al.,Complete Recovery in Plasma of Enzymes Lost from the Heart After Permanent Coronary Artery Occlusion in the Dog, Circulation 81:649-659 (1990).
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Roberts et al.,An Improved Basis for Enzymatic Estimation of Infarct Size, Circulation 52:743-754 (1975).
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Roe et al.,The Relationship Between Enzymatic and Histologic Estimates of the Extent of Myocardial Infarction in Conscious Dogs with Permanent Coronary Occlusion, Circulation 55:438-449 (1977).
Roe,Validity of Estimating Myocardial Infarct Size from Serial Measurements of Enzyme Activity in the Serum, Clin Chem 23:1807-1812 (1977).
Ryan et al.,The Creatine Kinase Curve Area and Peak Creatine Kinase After Acute Myocardial Infarction: Usefulness and Limitations, Am Heart J 101:162-168 (1981).
Schwerdt et al.,Optimised Function for Determining Time to Peak Creatine Kinase and Creatine Kinase-MB as Non-invasive Reperfusion Indicators After Thrombolytic Therapy in Acute Myocardial Infarction, Cardiovasc Res 24:328-334 (1990).
Seber et al., Nonlinear Regression. New York: John Wiley and Sons, 587-627 (1989).
Shell et al.,Early Estimation of Myocardial Damage in Conscious Dogs and Patients with Evolving Acute Myocardial Infarction, J Clin Invest 52:2579-2590 (1973).
Shell et al.,Quantitative Assessment of the Extent of Myocardial Infarction in the Conscious Dog by Means of Analysis of Serial Changes in Serum Creatine Phosphokinase Activity, J. Clin. Invest. 50: 2614-2625 (1971).
Sobel et al.,Estimation of In
Califf Robert M.
Christenson Robert H.
Duh Show-Hong
Newby L. Kristin
Ohman E. Magnus
Duke University
Marschel Ardin H.
Myers Bigel & Sibley & Sajovec
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