- Email: [email protected]
A Universal Language of the Heart
The American Journal of Medicine (2006) 119, 539-540
COMMENTARY
A Universal Language of the Heart By defining an object or a concept, we gain control over it. In fact, medical school education demands we absorb a seemingly endless supply of definitions that allow us to communicate with colleagues, a process that continues throughout our medical careers. Indeed, by defining a disease, clinicians and clinical scientists can then label patients—some would call it “making a diagnosis.” That label has important implications for the patient’s relationship to the medical community and to the rest of society. For example, some diagnoses can influence a patient’s work status; a myocardial infarction (MI) means early retirement for an airline pilot. In the clinical research sphere, a uniform definition of the disease to be studied is essential if the trial is to have any meaning and validity. Unfortunately, clinicians and clinical scientists often classify or interpret the characteristics of a particular disease differently, making it difficult—if not impossible—to compare the data that emerges from pharmacological, interventional, and epidemiological studies of similarly afflicted patients. Efforts to draw side-by-side inferences can be confounded whether the studies under scrutiny were each conducted within one country, in different countries, or on an international basis. This is exactly the case with MI. Past attempts to arrive at a standardized definition of this entity often failed because of evolving diagnostic technology or confusion surrounding the suggested definition. Not only has the lack of a consistent designation thwarted comparison of trial data, it also has snarled public health statistics and insurance company data. In an attempt to alleviate some of this confusion and arrive at an internationally-acceptable delineation, the American College of Cardiology and the European Society of Cardiology embarked on a consensus process, producing a document that was published simultaneously in the European Heart Journal and the Journal of the American College of Cardiology in 2000. This document has since been revised and is currently being modified again. It is anticipated that the latest version will be published and widely disseminated in 2007. In the meantime, a review of the existing report’s salient features is worthwhile. A brief summary follows: ●
MI, a diagnosis with major social and psychological implications, can be defined on the basis of clinical, pathological, electrocardiographic, biochemical, and epidemi-
0002-9343/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2006.05.021
●
●
●
●
AJM Theme Issue: Cardiology
ological aspects of the disease. Initially, the group studied the original World Health Organization definition, which stemmed from work done during the 1960s and 1970s.1 Any definition of MI must be tied to a number of qualifying prognostic factors pertaining to the index infarct. These are infarct size; the amount of surviving, functional left ventricular myocardium; the circumstances under which the infarct occurred (eg, during percutaneous transluminal coronary angioplasty/stent placement or spontaneously); and when myocardial necrosis occurred in relation to the observation time (ie, is the infarct new or old). Each of these factors carry important prognostic implications. The clinician needs to know more than the volume of myocardium infarcted during the period of examination. Myocardial ischemia results from an imbalance between perfusion supply and demand, and infarction occurs when ischemic injury to myocardial cells results in cellular death or necrosis. Chest, epigastric, arm, wrist, or jaw discomfort, either with exertion or at rest, suggests myocardial ischemia or necrosis. Discomfort associated with myocardial necrosis usually lasts at least 20 minutes. Associated symptoms can include nausea, vomiting, dyspnea, dizziness, and frank syncope. Occasionally, myocardial necrosis occurs in the absence of symptoms. Detection of myocardial necrosis requires recognition of the clinical picture and appropriate laboratory confirmation. Pathologists define MI as myocardial cell death secondary to prolonged ischemia. Myocardial necrosis can be recognized by an experienced observer during a careful histological examination. After the onset of myocardial ischemia, cell death is not immediate, requiring a finite period of time to develop (as little as 15 minutes). Approximately 6 hours must pass before the pathologist can confidently identify myocardial necrosis by standard macroscopic or light microscopic techniques. Complete necrosis of all cells within an ischemic myocardial zone requires 4 to 6 hours without collateral blood flow or therapeutic measures that decrease myocardial oxygen demand. Current laboratory techniques for the recognition of myocardial necrosis include measurement of creatine phosphokinase (total creatine phosphokinase and the MB fraction), myoglobin, and troponin (I and T). Myoglobin and
540
●
●
total CPK are less favored because they are not specific for myocardial necrosis, even though the early rise in blood myoglobin levels may be of some use in the emergency department (ED) for early diagnosis of myocardial injury. CPK-MB is more specific than either, although false positive and false negative results do occur. Troponin (I or T) has become the favored biomarker because it is more sensitive and specific than CPK-MB.2 Electrocardiographic signs of ischemia and non-ST-elevation infarction may be identical (eg, ST segment depression). ECG findings are more specific for ST-segment-elevation infarction. ECG changes indicative of myocardial ischemia that may lead to infarction include new or presumed new ST-segment elevation and/or STsegment depression, if the latter is accompanied by a rise in blood troponin values. ST elevation or depression or T wave inversion should be evident in two or more contiguous leads. An established, older MI produces a QR pattern in leads V1 through V3 that is at least 30 msec in duration and/or an abnormal Q wave (1 mm in depth) in any two contiguous leads of leads I, II, aVL, aVF, or V4 through V6.3 These findings are only valid in the absence of QRS confounders, such as left bundle branch block or Wolff-Parkinson-White syndrome. Because not all patients who develop myocardial necrosis have an abnormal ECG, a normal ECG does not rule-out MI. The new biomarkers are sensitive enough to detect myocardial necrosis in a very low range where ECG abnormalities may not be observed. Imaging techniques are useful for ruling out myocardial ischemia and MI in the ED, for identifying non-ischemic causes of chest discomfort, for defining post-infarction prognosis, and for identifying post-infarct complications, such as ventricular septal rupture or mitral regurgitation. Neither echocardiography nor radionuclide techniques can distinguish ischemia from infarction. However, the combination of an imaging study demonstrating recent abnormalities of perfusion or function and elevations in blood troponin levels does define an acute MI. The positive predictive value of either of these two techniques alone for defining MI is a disappointing 50%. As noted above, biomarker determination is still required in order to confirm the diagnosis of acute MI.4 Reliance on the greater sensitivity of the troponin assay
The American Journal of Medicine, Vol 119, No 7, July 2006 for pinpointing MI may create some initial consternation for epidemiologists, insurers, and others who subsist on public health statistics. The number of patients who will carry this diagnosis will increase substantially compared with earlier time periods when less sensitive biomarkers were used.1 Consider that a patient who formerly would have been diagnosed with an episode of unstable angina will now receive a diagnosis of MI, albeit a small one. Indeed, it may be difficult to compare current and future public health statistics with MI data from earlier eras. The introduction of the troponin-based definition of MI will increase the detectability of myocardial necrosis by 28% to 195%, depending on where the lower limit of normal was set for the blood troponin assay. Still, the consistent use of this marker will make it far easier to compare the results of new studies. And, it will provide a better sense of the extent of injury our patients have sustained. In this new environment, it is essential that we educate patients about the implications of the new troponin-related definition of MI. The small nature of many of these newly diagnosed infarcts and the associated modest increase in risk should be stressed. We must keep in mind that other prognostic factors remain important to the clinical decision-making process. Finally, healthcare planners and regulatory agencies also must recognize the influence the recent definition will have on the healthcare industry. In the end, we will all be better off. Joseph S. Alpert, MD Robert S. and Irene P. Flinn Professor of Medicine Special Assistant to the Dean University of Arizona College of Medicine Tucson.
References 1. Ischemic Heart Disease Registers. Report of the Fifth Working Group, Copenhagen. In: Report No. Eur 8201 (5). World Health Organization, Geneva, 1971. 2. Jaffe AS, Ravkilde J, Roberts R, et al. It’s time for a change to a troponin standard. Circulation. 2000;102:1216-1220. 3. Menown IB, Mackenzie G, Adgey AA. Optimizing the initial 12-lead electrocardiographic diagnosis of acute myocardial infarction. Eur Heart J. 2000;21:275-283. 4. The Joint European Society of Cardiology/American College of Cardiology Committee. Myocardial infarction redefined—a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J. 2000;21:1502-1513.
COMMENTARY
A Universal Language of the Heart By defining an object or a concept, we gain control over it. In fact, medical school education demands we absorb a seemingly endless supply of definitions that allow us to communicate with colleagues, a process that continues throughout our medical careers. Indeed, by defining a disease, clinicians and clinical scientists can then label patients—some would call it “making a diagnosis.” That label has important implications for the patient’s relationship to the medical community and to the rest of society. For example, some diagnoses can influence a patient’s work status; a myocardial infarction (MI) means early retirement for an airline pilot. In the clinical research sphere, a uniform definition of the disease to be studied is essential if the trial is to have any meaning and validity. Unfortunately, clinicians and clinical scientists often classify or interpret the characteristics of a particular disease differently, making it difficult—if not impossible—to compare the data that emerges from pharmacological, interventional, and epidemiological studies of similarly afflicted patients. Efforts to draw side-by-side inferences can be confounded whether the studies under scrutiny were each conducted within one country, in different countries, or on an international basis. This is exactly the case with MI. Past attempts to arrive at a standardized definition of this entity often failed because of evolving diagnostic technology or confusion surrounding the suggested definition. Not only has the lack of a consistent designation thwarted comparison of trial data, it also has snarled public health statistics and insurance company data. In an attempt to alleviate some of this confusion and arrive at an internationally-acceptable delineation, the American College of Cardiology and the European Society of Cardiology embarked on a consensus process, producing a document that was published simultaneously in the European Heart Journal and the Journal of the American College of Cardiology in 2000. This document has since been revised and is currently being modified again. It is anticipated that the latest version will be published and widely disseminated in 2007. In the meantime, a review of the existing report’s salient features is worthwhile. A brief summary follows: ●
MI, a diagnosis with major social and psychological implications, can be defined on the basis of clinical, pathological, electrocardiographic, biochemical, and epidemi-
0002-9343/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2006.05.021
●
●
●
●
AJM Theme Issue: Cardiology
ological aspects of the disease. Initially, the group studied the original World Health Organization definition, which stemmed from work done during the 1960s and 1970s.1 Any definition of MI must be tied to a number of qualifying prognostic factors pertaining to the index infarct. These are infarct size; the amount of surviving, functional left ventricular myocardium; the circumstances under which the infarct occurred (eg, during percutaneous transluminal coronary angioplasty/stent placement or spontaneously); and when myocardial necrosis occurred in relation to the observation time (ie, is the infarct new or old). Each of these factors carry important prognostic implications. The clinician needs to know more than the volume of myocardium infarcted during the period of examination. Myocardial ischemia results from an imbalance between perfusion supply and demand, and infarction occurs when ischemic injury to myocardial cells results in cellular death or necrosis. Chest, epigastric, arm, wrist, or jaw discomfort, either with exertion or at rest, suggests myocardial ischemia or necrosis. Discomfort associated with myocardial necrosis usually lasts at least 20 minutes. Associated symptoms can include nausea, vomiting, dyspnea, dizziness, and frank syncope. Occasionally, myocardial necrosis occurs in the absence of symptoms. Detection of myocardial necrosis requires recognition of the clinical picture and appropriate laboratory confirmation. Pathologists define MI as myocardial cell death secondary to prolonged ischemia. Myocardial necrosis can be recognized by an experienced observer during a careful histological examination. After the onset of myocardial ischemia, cell death is not immediate, requiring a finite period of time to develop (as little as 15 minutes). Approximately 6 hours must pass before the pathologist can confidently identify myocardial necrosis by standard macroscopic or light microscopic techniques. Complete necrosis of all cells within an ischemic myocardial zone requires 4 to 6 hours without collateral blood flow or therapeutic measures that decrease myocardial oxygen demand. Current laboratory techniques for the recognition of myocardial necrosis include measurement of creatine phosphokinase (total creatine phosphokinase and the MB fraction), myoglobin, and troponin (I and T). Myoglobin and
540
●
●
total CPK are less favored because they are not specific for myocardial necrosis, even though the early rise in blood myoglobin levels may be of some use in the emergency department (ED) for early diagnosis of myocardial injury. CPK-MB is more specific than either, although false positive and false negative results do occur. Troponin (I or T) has become the favored biomarker because it is more sensitive and specific than CPK-MB.2 Electrocardiographic signs of ischemia and non-ST-elevation infarction may be identical (eg, ST segment depression). ECG findings are more specific for ST-segment-elevation infarction. ECG changes indicative of myocardial ischemia that may lead to infarction include new or presumed new ST-segment elevation and/or STsegment depression, if the latter is accompanied by a rise in blood troponin values. ST elevation or depression or T wave inversion should be evident in two or more contiguous leads. An established, older MI produces a QR pattern in leads V1 through V3 that is at least 30 msec in duration and/or an abnormal Q wave (1 mm in depth) in any two contiguous leads of leads I, II, aVL, aVF, or V4 through V6.3 These findings are only valid in the absence of QRS confounders, such as left bundle branch block or Wolff-Parkinson-White syndrome. Because not all patients who develop myocardial necrosis have an abnormal ECG, a normal ECG does not rule-out MI. The new biomarkers are sensitive enough to detect myocardial necrosis in a very low range where ECG abnormalities may not be observed. Imaging techniques are useful for ruling out myocardial ischemia and MI in the ED, for identifying non-ischemic causes of chest discomfort, for defining post-infarction prognosis, and for identifying post-infarct complications, such as ventricular septal rupture or mitral regurgitation. Neither echocardiography nor radionuclide techniques can distinguish ischemia from infarction. However, the combination of an imaging study demonstrating recent abnormalities of perfusion or function and elevations in blood troponin levels does define an acute MI. The positive predictive value of either of these two techniques alone for defining MI is a disappointing 50%. As noted above, biomarker determination is still required in order to confirm the diagnosis of acute MI.4 Reliance on the greater sensitivity of the troponin assay
The American Journal of Medicine, Vol 119, No 7, July 2006 for pinpointing MI may create some initial consternation for epidemiologists, insurers, and others who subsist on public health statistics. The number of patients who will carry this diagnosis will increase substantially compared with earlier time periods when less sensitive biomarkers were used.1 Consider that a patient who formerly would have been diagnosed with an episode of unstable angina will now receive a diagnosis of MI, albeit a small one. Indeed, it may be difficult to compare current and future public health statistics with MI data from earlier eras. The introduction of the troponin-based definition of MI will increase the detectability of myocardial necrosis by 28% to 195%, depending on where the lower limit of normal was set for the blood troponin assay. Still, the consistent use of this marker will make it far easier to compare the results of new studies. And, it will provide a better sense of the extent of injury our patients have sustained. In this new environment, it is essential that we educate patients about the implications of the new troponin-related definition of MI. The small nature of many of these newly diagnosed infarcts and the associated modest increase in risk should be stressed. We must keep in mind that other prognostic factors remain important to the clinical decision-making process. Finally, healthcare planners and regulatory agencies also must recognize the influence the recent definition will have on the healthcare industry. In the end, we will all be better off. Joseph S. Alpert, MD Robert S. and Irene P. Flinn Professor of Medicine Special Assistant to the Dean University of Arizona College of Medicine Tucson.
References 1. Ischemic Heart Disease Registers. Report of the Fifth Working Group, Copenhagen. In: Report No. Eur 8201 (5). World Health Organization, Geneva, 1971. 2. Jaffe AS, Ravkilde J, Roberts R, et al. It’s time for a change to a troponin standard. Circulation. 2000;102:1216-1220. 3. Menown IB, Mackenzie G, Adgey AA. Optimizing the initial 12-lead electrocardiographic diagnosis of acute myocardial infarction. Eur Heart J. 2000;21:275-283. 4. The Joint European Society of Cardiology/American College of Cardiology Committee. Myocardial infarction redefined—a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J. 2000;21:1502-1513.