Rapid POC Marker Testing Strategy Facilitates Rapid Diagnosis of Chest Pain
Rapid POC Marker Testing Strategy Facilitates Rapid Diagnosis of Chest Pain
We compared a rapid, point-of-care multimarker protocol with a single and serial troponin I (TnI)-only protocol in 5,244 patients admitted to the emergency department with chest pain. The diagnosis of acute myocardial infarction (AMI) was based on a doubling myoglobin level accompanied by at least a 50% increase in the creatine kinase (CK)-MB level with no detectable TnI; a doubling of myoglobin level together with any detectable TnI; or a TnI level of 0.4 ng/mL (0.4 μg/L) or more, irrespective of myoglobin or CK-MB results. By using these new criteria, 145 of 148 cases were positive for AMI (positive predictive value [PPV], 92.4%) and 3 were negative, which were also negative by the core laboratory TnI assay. Twelve confirmed non-AMI cases were positive by the new protocol, with 10 of 12 confirmed by the core laboratory as positive for TnI. The negative predictive value (NPV) was 99.9%; the overall diagnostic accuracy was 99.7%. The TnI-only protocol had a sensitivity of 68.2% with an NPV of 99.1%. With lower TnI-only cutoffs, 4 patients had false-negative results, and a PPV of 36.4% was observed. Our rapid multimarker protocol seems superior to a TnI-only approach for rapidly triaging patients with chest pain or AMI.
According to American Heart Association statistics, cardiovascular disease accounted for more than one third of all deaths in 2004 in the United States, with death and disability from acute myocardial infarctions (AMI), or heart attack, continuing to be major health concerns. Indeed, it is estimated that in the United States, nearly 1.1 million AMIs occur each year, with approximately 515,000 associated deaths. Because approximately half of these deaths occur within hours of onset of symptoms (usually outside the hospital setting), we believe that for patients admitted to the emergency department (ED), rapid diagnosis and early treatment of AMI are essential for reducing associated morbidity and mortality.
Nearly 8 million patients with chest pain are evaluated each year by EDs in the United States, with approximately 50% admitted to the hospital for further observation and evaluation. Surprisingly, only about 30% of the hospitalized patients end up with a cardiac-related diagnosis. In addition, current literature suggests that although the use of patient history, physical examination findings, electrocardiogram (ECG) findings, and other test results significantly improves the accuracy of diagnosis of acute coronary syndrome (ACS), these tools still miss a significant portion of patients with AMI, especially patients with non–ST segment elevation MI (STEMI). We conclude that false-positive (FP) AMI screening results in the ED drive unnecessary hospital admissions, and false-negative (FN) AMI screening findings can result in a missed diagnosis, which is unacceptable. Clearly, given the need to make more accurate evidence-based diagnostic and triage decisions, the use of a more rapid screening protocol in the ED with biochemical cardiac markers designed for patients admitted with early, middle, and late chest pain is required.
The cardiac markers routinely used to diagnose and risk stratify patients with chest pain include myoglobin, creatine kinase (CK)-MB, and cardiac troponins T (cTnT) and I (cTnI). These cardiac markers are released into the blood following irreversible myocardial necrosis and are known to have the following unique release characteristics and kinetics: (1) The myoglobin level elevates in 1 to 2 hours after the onset of symptoms; measurement is useful in patients who come to the ED soon after the onset of chest pain (early chest pain). (2) Cardiac troponins can be detected within 3 to 4 hours after symptom onset; measurement is useful in patients who come to the ED a longer time after symptom onset (middle and late chest pain). (3) The CK-MB level is elevated within 5 to 6 hours after onset of symptoms; measurement is useful in patients who come to the ED several hours after the onset of chest pain (late chest pain). However, these markers must be ordered as a panel in the ED because no single marker meets all criteria for an ideal marker of AMI diagnosis for all patients who arrive at the ED at various times after the onset of the symptoms.
As reviewed by Karras and Kane, CK-MB levels seem to be normal in one fourth to one half of patients with AMI at the time of ED admission; however, the CK-MB level has an excellent diagnostic value at 6 or more hours after the onset of symptoms. Like CK-MB, cardiac troponin is really best regarded as a late marker for AMI because values are generally elevated between 6 and 24 hours after an AMI. Although myoglobin seems to be highly sensitive for patients with early chest pain, it is of marginal use in patients with middle to late chest pain.
Because an AMI is a biochemical event involving irreversible damage to a cluster of myocytes in the heart, a timed protocol for testing is required to detect clinically significant changes in the blood levels of the aforementioned cardiac markers. Hence, because of variation the time of admission to the ED of patients with chest pain and the narrow windows of the 3 aforementioned cardiac markers, it is no surprise that a timed multisample, multimarker screening strategy has been shown to be extremely useful in rapid diagnosis of AMI in a number of studies.
With these considerations in mind, current American College of Cardiology/American Heart Association guidelines emphasize a rapid turnaround time in the diagnosis of possible AMI and require or recommend that the results be available within 60 minutes, preferably within 30 minutes. Clearly, the turnaround time required for cardiac testing must coincide with the chest pain protocol ED physicians decide to use. These guidelines further state that point-of-care (POC) systems, if implemented at the bedside, have the advantage of reducing delays due to transportation and processing in a central laboratory and can eliminate delays due to lack of 24-hour availability of central laboratory assays. Consequently, we present an evaluation of a multiple marker approach combined with obtaining serial specimens and POC testing that provides results in approximately 15 minutes. Our study is unique because we applied this multimarker algorithm with cases positive for AMI based on a TnI level of 0.4 ng/mL (0.4 μg/L) or more in any sample or a doubling of the myoglobin level between sequential specimens with detectable TnI or with an increase of 50% or more in CK-MB level without detectable TnI in any specimen.
We compared a rapid, point-of-care multimarker protocol with a single and serial troponin I (TnI)-only protocol in 5,244 patients admitted to the emergency department with chest pain. The diagnosis of acute myocardial infarction (AMI) was based on a doubling myoglobin level accompanied by at least a 50% increase in the creatine kinase (CK)-MB level with no detectable TnI; a doubling of myoglobin level together with any detectable TnI; or a TnI level of 0.4 ng/mL (0.4 μg/L) or more, irrespective of myoglobin or CK-MB results. By using these new criteria, 145 of 148 cases were positive for AMI (positive predictive value [PPV], 92.4%) and 3 were negative, which were also negative by the core laboratory TnI assay. Twelve confirmed non-AMI cases were positive by the new protocol, with 10 of 12 confirmed by the core laboratory as positive for TnI. The negative predictive value (NPV) was 99.9%; the overall diagnostic accuracy was 99.7%. The TnI-only protocol had a sensitivity of 68.2% with an NPV of 99.1%. With lower TnI-only cutoffs, 4 patients had false-negative results, and a PPV of 36.4% was observed. Our rapid multimarker protocol seems superior to a TnI-only approach for rapidly triaging patients with chest pain or AMI.
According to American Heart Association statistics, cardiovascular disease accounted for more than one third of all deaths in 2004 in the United States, with death and disability from acute myocardial infarctions (AMI), or heart attack, continuing to be major health concerns. Indeed, it is estimated that in the United States, nearly 1.1 million AMIs occur each year, with approximately 515,000 associated deaths. Because approximately half of these deaths occur within hours of onset of symptoms (usually outside the hospital setting), we believe that for patients admitted to the emergency department (ED), rapid diagnosis and early treatment of AMI are essential for reducing associated morbidity and mortality.
Nearly 8 million patients with chest pain are evaluated each year by EDs in the United States, with approximately 50% admitted to the hospital for further observation and evaluation. Surprisingly, only about 30% of the hospitalized patients end up with a cardiac-related diagnosis. In addition, current literature suggests that although the use of patient history, physical examination findings, electrocardiogram (ECG) findings, and other test results significantly improves the accuracy of diagnosis of acute coronary syndrome (ACS), these tools still miss a significant portion of patients with AMI, especially patients with non–ST segment elevation MI (STEMI). We conclude that false-positive (FP) AMI screening results in the ED drive unnecessary hospital admissions, and false-negative (FN) AMI screening findings can result in a missed diagnosis, which is unacceptable. Clearly, given the need to make more accurate evidence-based diagnostic and triage decisions, the use of a more rapid screening protocol in the ED with biochemical cardiac markers designed for patients admitted with early, middle, and late chest pain is required.
The cardiac markers routinely used to diagnose and risk stratify patients with chest pain include myoglobin, creatine kinase (CK)-MB, and cardiac troponins T (cTnT) and I (cTnI). These cardiac markers are released into the blood following irreversible myocardial necrosis and are known to have the following unique release characteristics and kinetics: (1) The myoglobin level elevates in 1 to 2 hours after the onset of symptoms; measurement is useful in patients who come to the ED soon after the onset of chest pain (early chest pain). (2) Cardiac troponins can be detected within 3 to 4 hours after symptom onset; measurement is useful in patients who come to the ED a longer time after symptom onset (middle and late chest pain). (3) The CK-MB level is elevated within 5 to 6 hours after onset of symptoms; measurement is useful in patients who come to the ED several hours after the onset of chest pain (late chest pain). However, these markers must be ordered as a panel in the ED because no single marker meets all criteria for an ideal marker of AMI diagnosis for all patients who arrive at the ED at various times after the onset of the symptoms.
As reviewed by Karras and Kane, CK-MB levels seem to be normal in one fourth to one half of patients with AMI at the time of ED admission; however, the CK-MB level has an excellent diagnostic value at 6 or more hours after the onset of symptoms. Like CK-MB, cardiac troponin is really best regarded as a late marker for AMI because values are generally elevated between 6 and 24 hours after an AMI. Although myoglobin seems to be highly sensitive for patients with early chest pain, it is of marginal use in patients with middle to late chest pain.
Because an AMI is a biochemical event involving irreversible damage to a cluster of myocytes in the heart, a timed protocol for testing is required to detect clinically significant changes in the blood levels of the aforementioned cardiac markers. Hence, because of variation the time of admission to the ED of patients with chest pain and the narrow windows of the 3 aforementioned cardiac markers, it is no surprise that a timed multisample, multimarker screening strategy has been shown to be extremely useful in rapid diagnosis of AMI in a number of studies.
With these considerations in mind, current American College of Cardiology/American Heart Association guidelines emphasize a rapid turnaround time in the diagnosis of possible AMI and require or recommend that the results be available within 60 minutes, preferably within 30 minutes. Clearly, the turnaround time required for cardiac testing must coincide with the chest pain protocol ED physicians decide to use. These guidelines further state that point-of-care (POC) systems, if implemented at the bedside, have the advantage of reducing delays due to transportation and processing in a central laboratory and can eliminate delays due to lack of 24-hour availability of central laboratory assays. Consequently, we present an evaluation of a multiple marker approach combined with obtaining serial specimens and POC testing that provides results in approximately 15 minutes. Our study is unique because we applied this multimarker algorithm with cases positive for AMI based on a TnI level of 0.4 ng/mL (0.4 μg/L) or more in any sample or a doubling of the myoglobin level between sequential specimens with detectable TnI or with an increase of 50% or more in CK-MB level without detectable TnI in any specimen.
