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Old age, left bundle branch block and acute myocardial infarction: a vexing and lethal combination∗
Journal of the American College of Cardiology © 2000 by the American College of Cardiology Published by Elsevier Science Inc.
EDITORIAL COMMENT
Old Age, Left Bundle Branch Block and Acute Myocardial Infarction: A Vexing and Lethal Combination* Gottlieb C. Friesinger, II, MD, MACC, Raphael F. Smith, MD, FACC Nashville, Tennessee The evolution of reperfusion therapy in the treatment of acute myocardial infarction (AMI) has highlighted the extraordinary importance of rapid and accurate diagnosis of infarcts due to thrombosis of a major epicardial vessel, the so-called Q-Wave Myocardial Infarction or Transmural Myocardial Infarction. The presence of AMI can be established by a wide variety of diagnostic tests, but the narrow temporal window for significant myocardial salvage with reperfusion dictates that the clinical presentation and the 12-lead ECG remain the principal tools available to make the decision about reperfusion therapy. Although reperfusion therapy has been embraced enthusiastically for treatment of all ST segment elevation AMI, the benefit is greatest in those subsets of patients with the highest absolute risk for mortality, anterior myocardial infarction and subsets of inferior infarction and other locations (1,2). In subsets of very-low-risk infarcts, mortality benefit for reperfusion therapy is marginal or has not been demonstrated (3). Age is a powerful determinant of outcome (4 –7). The mortality risk of AMI increases almost logarithmically with age and 70% of fatal infarcts occur in patients over the age of 65 years. These well-known features concerning AMI and reperfusion therapy make the observational study of Shlipak et al. (8), concerning the treatment and outcomes of left bundle branch block (LBBB) in patients with AMI reported in this issue of the Journal, of particular interest. See page 706 Regardless of the changes and improvements in the logistics of therapy in AMI, better outcomes will always be contingent on prompt recognition of the patients who are candidates for reperfusion therapy, particularly those at high risk. *Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. From Vanderbilt University, Nashville Veterans Administration Medical Center, Nashville, Tennessee.
Vol. 36, No. 3, 2000 ISSN 0735-1097/00/$20.00 PII S0735-1097(00)00801-9
The current study. The National Registry of Myocardial Infarction 2 (NRMI-2) is a voluntary prospective observational registry of 772,586 patients with AMI admitted to 1,470 hospitals in all 50 states in the U.S. (8). The data were collected between 1994 and 1998. This rich database describes contemporary practice and provides information on an extraordinary subset of 29,585 patients with LBBB and AMI. This huge sample of LBBB patients constitutes 3.7% of the total NRMI-2 infarct population. In keeping with the fact that LBBB is often associated with large anterior myocardial infarctions and the mean age of these patients was 76.4 years, the mortality rate of 22%, was extremely high. Other notable attributes of the sample include a high prevalence of major co-morbidity; congestive heart failure in nearly 40%, diabetes in 37% and hypertension in over half of the sample population. Not surprising in light of the advanced age, half of the sample population were female in contrast to the gender mix in younger subsets of AMI in which male patients predominate. A particularly important feature is the extremely low utilization of reperfusion therapy; only 8.4% of the sample population had any form of reperfusion. Since the absolute benefit (e.g., number needed to treat to prevent one death or number of lives saved per thousand patients treated) of reperfusion therapy is greatest in the infarcts of highest risk, this is a particularly disturbing characteristic of contemporary practice. The investigators’ analyses provide important explanations for the phenomenon of failure to treat. Nearly half of the patients (47%) presented without chest pain. The absence of chest pain (ischemic discomfort) is a frequent feature in elderly patients with AMI (9 –12). Although no data related to the actual presenting complaints are given, it is reasonable to assume that the majority had dyspnea, the common presenting complaint in elderly patients with AMI. The combination of a nondiagnostic ECG (LBBB) and the absence of chest pain undoubtedly discouraged the use of reperfusion therapy in this very high-risk population. An extremely small proportion, 2.6%, without chest pain received reperfusion therapy. However, only 13.6% of patients with chest pain received reperfusion therapy. Other treatment and diagnostic procedures were used significantly less often in the non– chest pain group: aspirin, 73% versus 55%; beta-blocker, 33% versus 18%; heparin, 69% versus 48%; elective coronary arteriography, 33% versus 16%; elective percutaneous transluminal coronary angioplasty, 12% vs. 4%; and elective coronary artery bypass; 6% vs. 3%. Only angiotensin-converting enzyme inhibitors were used with equal frequency (30% vs. 32%). Left bundle branch block was found in 2.7% of patients with AMI ⬍65 years of age and in 10.5% in those ⬎75 years old. In the LBBB-AMI group, 37% ⬍65 years presented with chest pain, while 50% of those ⬎75 years had no chest discomfort. In a larger context, the LBBB-AMI group reflects the
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clinical issues in the old age group with AMI; namely, presenting complaints tend to be atypical and ECG findings tend to be nondiagnostic. A frequent ECG finding is ST segment depression with the development of non-Q-wave infarct (13). As confirmed by this report, these “atypical” features (for young patients!) do not connote a lower mortality rate in the elderly. We must improve our recognition of the clinical presentation of AMI in the elderly; “atypical” presentations in reference to symptoms and ECG findings should be considered frequent and the norm. The clear message from the work of Shlipak et al. (8) is the need to lower the diagnostic threshold for considering AMI when LBBB is present, especially in the older patient. Can AMI be diagnosed by ECG when LBBB is present? Better tests for AMI that can be immediately available in the emergency department are being intensively investigated but, in the near future, the 12-lead ECG will remain the primary diagnostic tool to assess the presence of epicardial coronary arterial thrombosis and make the decision for reperfusion therapy. With LBBB, the course of ventricular activation is altered, which secondarily affects ventricular repolarization. The QRS, ST-segment and T wave of the ECG are always affected by LBBB. More often than not, the early signs of AMI will be obscured by the changes due to the conduction abnormality. The prevalence of LBBB and other cardiac conduction abnormalities increases with age. While LBBB due to “sclerodegenerative” disease (14 –16) or senile amyloidosis (17) can occur in the absence of other structural heart disease or cardiac symptoms (18), detailed clinicopathologic studies (14 – 17) show that LBBB increases in the elderly and is more often associated with advanced cardiac disease of several types. Thus, LBBB is a marker both of age and severe heart disease but not exclusively coronary disease. Multiple studies have evaluated the ability to diagnose AMI when LBBB is present (19 –24). The work of Sgarbossa et al. (24) is instructive in this regard. They developed diagnostic criteria for AMI when LBBB was present using data from the GUSTO-1 Trial (the derivation or training sample) and from a control population with LBBB and stable ischemic heart disease (the validation sample). Three ECG criteria based on ST segment displacement were found to have independent diagnostic value (see legend of the Fig. 1). The three criteria were assigned index scores and incorporated in a diagnostic algorithm. This algorithm was found to have a sensitivity of 78% and a specificity of 90% in the derivation/training sample. The diagnostic specificity remained high, 96%, but the sensitivity was quite low, 36%, when applied to the validation sample, a small group of 45 patients. In an earlier report, Shlipak et al. (25) tested the Sgarbossa algorithm and other ECG criteria for myocardial infarctions in patients with LBBB and found that none effectively distinguished the patients with myocardial infarction from those with other diagnoses. A possible explanation for these differing results is that the Sgarbossa algo-
JACC Vol. 36, No. 3, 2000 September 2000:713–6
rithm was derived and validated in a cohort of patients with LBBB from the GUSTO-1 Trial, which represented only 0.5% of the 26,003 patients enrolled in the trial (26). This low percentage of LBBB in AMI suggests that the cohort studied by Sgarbossa et al. (24) was highly selected and may not be representative of the universe of patients with this combination of abnormalities. The reported studies of LBBB-AMI suggest that an unknown, albeit small, subset of patients have ECG changes that are indicative of AMI and in this group these findings could lead to immediate fibrinolytic therapy. More research is needed to confirm, refine and determine the frequency of ECG findings of LBBB that may indicate AMI. For example, included in such studies would be the evaluation of serial ECGs, taken over a brief period of 30 to 40 min, to determine if fluctuating repolarization changes may enhance the sensitivity of the 12-lead ECG since repolarization changes are dynamic during the early course of transmural myocardial infarction. What might be done to resolve this issue? No simple approach to resolution is feasible. What can be done immediately and what must be done in order to provide better care is to have a much lower threshold for the suspicion of AMI in all elderly patients with nonspecific cardiac complaints, particularly dyspnea, but with a wide variety of complaints, which are common in AMI in the elderly. When LBBB is present, the suspicion of AMI should be increased, efforts should be made to obtain previous ECGs and particular attention should be paid to subtle changes in repolarization, which will lead to more definitive tests. In patients in whom the suspicion of AMI is high, reperfusion therapy should be seriously considered because of the high mortality of AMI-LBBB in elderly patients. Obviously, a highly individualized approach is needed with careful consideration of the patient’s general health activity status and co-morbidity (26). If fibrinolytic therapy is selected, streptokinase has been demonstrated in all studies to have a lower risk of cerebral hemorrhage—the most dreaded complication of therapy—which increases in the elderly population (27,28). In addition, decision analysis using the GISSI-1 database has demonstrated fibrinolysis to be cost effective even when the probability of diagnosis of AMI is relatively low in elderly patients because the mortality is so high and the mortality benefit was great (33% to 29% reduction) (29). In patients with LBBB in whom the diagnosis is probable but not certain, emergency cardiac catheterization both for diagnosis and to plan management is justified. Achieving immediate reperfusion with a catheter-based intervention in this setting is almost certainly more effective than thrombolytic therapy and avoids the risk of central nervous system (CNS) hemorrhage. The NRMI-2 registry emphasizes the approach that could be utilized to clarify the problem. Registries are powerful tools to assess these issues. A large registry of patients with LBBB who are evaluated in
JACC Vol. 36, No. 3, 2000 September 2000:713–6
Figure 1. The Venn diagram depicts the universe of patients with LBBB evaluated in the emergency department and the relationships between LBBB and AMI. Categories/subsets emphasize the wide range of possibilities that exist. The Venn diagram is discussed in the text. The LBBB with new ST displacement subset emphasizes there may be ECG changes helpful in diagnosing AMI. The scoring system of Sgarbossa is one approach. ST-segment elevation ⬎1 mm and concordant with QRS complex, 5 points; ST-segment depression ⬎1 mm in lead V1, V2, and V3, 3 points; ST-segment elevation ⬎5 mm and discordant with QRS complex, 2 points; an ECG score of 3 is used to diagnose AMI; 2 is suspicious for AMI.
emergency departments with a variety of complaints could constitute the study sample. The protocol for such a study would include clinical presentation, ECG findings (particularly study of serial ECGs) and the management selected, as well as outcomes. As in any good registry study, definitions would have to be agreed on and used in a prescriptive fashion. The Venn diagram (Fig. 1) provides a framework to discuss the multiple facets of the problem and management approaches. It is not intended to be prescriptive but to emphasize the fact that multiple permutations exist that call for fastidiously collected data to better define management strategies. If the Sgarbossa criteria were confirmed, patients in subsets A, B and C would proceed to revascularization. Subsets D, E and F pose the dilemma emphasized in the current Shlipak et al. (8) article. Patients in the D subgroup were more likely (13.2%) than patients in the E subgroup (2.6%) to receive reperfusion therapy, but both sets had unacceptably low attempts at reperfusion. Patients in the F subset would represent those with AMI who had confusing symptoms that were primarily not cardiac, such as fatigue, “generally not well,” CNS manifestations, among others— presentations that are common in elderly patients with AMI. Subset G represents patients who have an acute coronary syndrome without myocardial necrosis but who require energetic workup and care to prevent AMI. Subset H includes a highly problematic group of patients, some of whom would have acute coronary syndromes. The remaining LBBB patients (large circle) will represent a wide array of clinical entities including stable or unstable coronary syndromes. Since LBBB patients as a group are older, co-morbidity
Friesinger and Smith Editorial Comment
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and frailty will be deterrents to aggressive evaluations and workup. However, in the absence of contraindications, urgent coronary arteriography would provide the pathway to better treatment in many patients. Although the use of arteriography in the elderly is increasing (30,31), currently in the U.S. the procedure is used more frequently in young, low-risk patients with AMI in whom the benefit will not be great (32,33). Acute myocardial infarction in the elderly with associated frailty and co-morbidity will always require highly individualized, thoughtful clinical judgment. The heterogeneity of the elderly and the heterogeneity of the emergency department patients with LBBB assure that randomized control trials will contribute little to the resolution of these problems (34). A carefully conceived registry study, as the current NRMI-2 study illustrates, can be an effective approach utilizing the scheme outlined in the Venn diagram (35). Shlipak et al. (8) have provided valuable information on an important problem, LBBB in patients with AMI, with their analysis of the extraordinary NRMI-2 database of ⬎29,000 patients. By focusing attention on the current management of this problematic group of patients, they expose a much larger problem in cardiology practice; namely the gross underutilization of reperfusion therapy in the elderly population with AMI. In this high-risk population, not only are better ECG criteria and other diagnostic approaches needed to diagnose AMI in the emergency department, but it is reasonable to use emergent coronary arteriography more frequently for diagnosis and to plan management. Since randomized control trials will not be done in the elderly, the registry method should be used and could help unravel difficult management problems. With ⬎70 million baby boomers soon to enter old age, the issues brought into focus by Shlipak et al. (8) and commented on in this editorial will become even more pressing. Addendum. A recent publication, (Thieman DR, Coresh J, Schulman S, et. al. Lack of benefit of intravenous thrombolysis in patients with myocardial infarction who are older than 75 years, Circulation 2000;101:2239 –2246 2000) reports the lack of benefit and potential adverse effects of fibrinolytic therapy in 7,864 Medicare patients, age 65 to 86 years, with the primary discharge diagnosis of acute myocardial infarction. This observational study needs to be confirmed but the data presented further emphasizes the complexities of the issues involved in elderly patients with acute myocardial infarction and makes catheter-based reperfusion procedures, as discussed in this editorial, more appealing. Reprint requests and correspondence: Dr. Gottlieb C. Friesinger II, Betty and Jack Bailey Professor of Cardiology, Vanderbilt University, Nashville, Tennessee 37232. E-mail: [email protected].
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REFERENCES 1. ISIS-2 Second International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction. ISIS-2. Lancet 1988;2:349 – 60. 2. GISSI-1. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;1:397– 402. 3. Bates ER. Revisiting reperfusion therapy in inferior myocardial infarction. J Am Coll Cardiol 1997;30:334 – 42. 4. Maggioni AP, Maseri A, Fresco C, et al. Age-related increase in mortality infarctions treated with thrombolysis. N Engl J Med 1993; 329:1331– 8. 5. Lee KL, Woodlief LH, Topol DJ, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction: results from an international trial of 41,021 patients. Circulation 1995;91:1659 – 68. 6. Goldberg RJ, Gore JM, Gurwitz JH, et al. The impact of age on the incidence and prognosis of initial myocardial infarction: the Worcester Heart Attack Study. Am Heart J 1989;117:543–9. 7. Weaver WD, Litwin PE, Martin JS, et al. Effect of age on use of thrombolytic therapy and mortality in acute myocardial infarction: the MITI Project Group. J Am Coll Cardiol 1991;18:657– 62. 8. Shlipak MG, Go AS, Frederick PD, et al. Treatment and outcomes of left bundle-branch block patients with myocardial infarction who present without chest pain. J Am Coll Cardiol 2000;36:706 –12. 9. Pathy MS. Clinical presentation of myocardial infection in the elderly. Br Heart J 1967;29:190 –9. 10. Nadelman J, Fishman WH, Ooi WL, et al. Prevalence, incidence and prognosis of recognized and unrecognized myocardial infarction in persons aged 75 years or older: the Bronx Aging Study, Am J Cardiol 1990;66:533–7. 11. Miller PF, Sheps DS, Bragdon EE, et al. Aging and pain perception in ischemic heart disease. Am Heart J 1990;120:22–30. 12. Sigurdsson E, Thorgeirsson G, Sigvaldason H, et al. Unrecognized myocardial infarction: epidemiology, clinical characteristics, and the prognostic role of angina pectoris: the Reykjavik Study. Ann Intern Med 1995;122:96 –102. 13. Krumholz HM, Friesinger GC, Cook EF, et al. Relationship of age with eligibility or thrombolytic therapy and mortality among patients with suspected acute myocardial infarction. J Am Geriatr Soc 1994; 42:127–31. 14. Lev M. The pathology of complete heart block. Prog Cardiovasc Dis 1964;6:317–26. 15. Lenegre J. Etiology and pathology of bilateral bundle branch clock in relation to complete heart block. Prog Cardiovasc Dis 1964;6:409 – 44. 16. Saguaro M, Horace K, Ohkawa S, Shimada H. A clinico-pathological study of the heart in the aged: the morphological classification of the 1,000 consecutive autopsy cases. Jpn Heart J 1975;16:526 –37. 17. Johansson B, Westermark P. Senile systemic amyloidosis: a clinicopathological study of twelve patients with massive amyloid infiltration. Int J Cardiol 1991;32:83–92.
JACC Vol. 36, No. 3, 2000 September 2000:713–6 18. Smith RF, Harthorne JW, Sanders CA. Acquired bundle branch block in a healthy population. Am Heart J 1970;80:746 –51. 19. Cabrera E, Friedland C. La onda de activacio´n ventricualr en el bloquero de rama izquierda con infarcto: un nuevo signo electrocardiogra´fico. Arch Inst Cardiol Mex 1953;23:441– 60. 20. Besoaı´n-Santander M, Go´mez-Ebensperguer G. Electrocardiographic diagnosis of myocardial infarction in cases of complete left bundle branch block. Am Heart J 1960;60:886 –97. 21. Doucet P, Walsh TJ, Massie E. A vectrocardiographic and electrocardiographic study of left bundle branch block with myocardial infarction. Am J Cardiol 1966;17:171–9. 22. Wackers FJ. The diagnosis of myocardial infarction in the presence of complete left bundle branch block. Cardiol Clin 1987;5:393– 401. 23. Hands ME, Cook EF, Stone PH, et al. Electrocardiographic diagnosis of myocardial infarction in the presence of complete left bundle branch block. Am Heart J 1988;116:23–31. 24. Sgarbossa EB, Pinski SL, Barbagelata A, et al. Electrocardiographic diagnosis of evolving acute myocardial infarction in the presence of left bundle-branch block. N Engl J Med 1996;334:481–7. 25. Shlipak MG, Lyons WL, Go AS, Chou TM, Evans GT, Browner WS. Should the electrocardiogram be used to guide therapy for patients with left bundle-branch block and suspected myocardial infarction? JAMA 1999;281:714 –9. 26. Welch HG, Albertsen PC, Nease RF, et al. Estimating treatment benefits for the elderly: the effect of competing risks. Ann Intern Med 1996;124:577. 27. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673– 82. 28. Simoons ML, Maggioni AP, Knatterud G, et al. Individual risk assessment for intracranial hermorrhage during thrombolytic therapy. Lancet 1995;342:1523– 8. 29. Krumholz HM, Pasternak RC, Weinstein MC, et al. Cost effectiveness of thrombolytic therapy with streptokinase in elderly patients with suspected acute myocardial infarction. N Engl J Med 1992;327:7–13. 30. Singh M, Mathew V, Garratt KN, et al. Effect of age on the outcome of angioplasty for acute myocardial infarction among patients treated at the Mayo Clinic. Am J Med 2000;108:187–92. 31. DeGeare VS, Grines CL. Primary percutaneous intervention in octogenarians with acute myocardial infarction: the treatment of choice. Am J Med 2000;108:257– 8. 32. Pilote L, Miller DP, Clift RM, et al. Determinants of the use of coronary arteriography and revascularization after thrombolysis for acute myocardial infarction. N Engl J Med 1996;335:1198 –1205. 33. Bates DW, Miller E, Bernstein S, et al. Coronary angiography and angioplasty after acute myocardial infarction. Ann Intern Med 1997; 126:539 –50. 34. Prabhat JHA, Deboer D, Sykora K, et al. Characteristics and mortality outcomes of thrombolysis trial participants and nonparticipants: a population-based comparison. J Am Coll Cardiol 1996;27:1335– 42. 35. Black N. Why we need observational studies to evaluate the effectiveness of health care. BMJ 1966;312:1215– 8.
EDITORIAL COMMENT
Old Age, Left Bundle Branch Block and Acute Myocardial Infarction: A Vexing and Lethal Combination* Gottlieb C. Friesinger, II, MD, MACC, Raphael F. Smith, MD, FACC Nashville, Tennessee The evolution of reperfusion therapy in the treatment of acute myocardial infarction (AMI) has highlighted the extraordinary importance of rapid and accurate diagnosis of infarcts due to thrombosis of a major epicardial vessel, the so-called Q-Wave Myocardial Infarction or Transmural Myocardial Infarction. The presence of AMI can be established by a wide variety of diagnostic tests, but the narrow temporal window for significant myocardial salvage with reperfusion dictates that the clinical presentation and the 12-lead ECG remain the principal tools available to make the decision about reperfusion therapy. Although reperfusion therapy has been embraced enthusiastically for treatment of all ST segment elevation AMI, the benefit is greatest in those subsets of patients with the highest absolute risk for mortality, anterior myocardial infarction and subsets of inferior infarction and other locations (1,2). In subsets of very-low-risk infarcts, mortality benefit for reperfusion therapy is marginal or has not been demonstrated (3). Age is a powerful determinant of outcome (4 –7). The mortality risk of AMI increases almost logarithmically with age and 70% of fatal infarcts occur in patients over the age of 65 years. These well-known features concerning AMI and reperfusion therapy make the observational study of Shlipak et al. (8), concerning the treatment and outcomes of left bundle branch block (LBBB) in patients with AMI reported in this issue of the Journal, of particular interest. See page 706 Regardless of the changes and improvements in the logistics of therapy in AMI, better outcomes will always be contingent on prompt recognition of the patients who are candidates for reperfusion therapy, particularly those at high risk. *Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. From Vanderbilt University, Nashville Veterans Administration Medical Center, Nashville, Tennessee.
Vol. 36, No. 3, 2000 ISSN 0735-1097/00/$20.00 PII S0735-1097(00)00801-9
The current study. The National Registry of Myocardial Infarction 2 (NRMI-2) is a voluntary prospective observational registry of 772,586 patients with AMI admitted to 1,470 hospitals in all 50 states in the U.S. (8). The data were collected between 1994 and 1998. This rich database describes contemporary practice and provides information on an extraordinary subset of 29,585 patients with LBBB and AMI. This huge sample of LBBB patients constitutes 3.7% of the total NRMI-2 infarct population. In keeping with the fact that LBBB is often associated with large anterior myocardial infarctions and the mean age of these patients was 76.4 years, the mortality rate of 22%, was extremely high. Other notable attributes of the sample include a high prevalence of major co-morbidity; congestive heart failure in nearly 40%, diabetes in 37% and hypertension in over half of the sample population. Not surprising in light of the advanced age, half of the sample population were female in contrast to the gender mix in younger subsets of AMI in which male patients predominate. A particularly important feature is the extremely low utilization of reperfusion therapy; only 8.4% of the sample population had any form of reperfusion. Since the absolute benefit (e.g., number needed to treat to prevent one death or number of lives saved per thousand patients treated) of reperfusion therapy is greatest in the infarcts of highest risk, this is a particularly disturbing characteristic of contemporary practice. The investigators’ analyses provide important explanations for the phenomenon of failure to treat. Nearly half of the patients (47%) presented without chest pain. The absence of chest pain (ischemic discomfort) is a frequent feature in elderly patients with AMI (9 –12). Although no data related to the actual presenting complaints are given, it is reasonable to assume that the majority had dyspnea, the common presenting complaint in elderly patients with AMI. The combination of a nondiagnostic ECG (LBBB) and the absence of chest pain undoubtedly discouraged the use of reperfusion therapy in this very high-risk population. An extremely small proportion, 2.6%, without chest pain received reperfusion therapy. However, only 13.6% of patients with chest pain received reperfusion therapy. Other treatment and diagnostic procedures were used significantly less often in the non– chest pain group: aspirin, 73% versus 55%; beta-blocker, 33% versus 18%; heparin, 69% versus 48%; elective coronary arteriography, 33% versus 16%; elective percutaneous transluminal coronary angioplasty, 12% vs. 4%; and elective coronary artery bypass; 6% vs. 3%. Only angiotensin-converting enzyme inhibitors were used with equal frequency (30% vs. 32%). Left bundle branch block was found in 2.7% of patients with AMI ⬍65 years of age and in 10.5% in those ⬎75 years old. In the LBBB-AMI group, 37% ⬍65 years presented with chest pain, while 50% of those ⬎75 years had no chest discomfort. In a larger context, the LBBB-AMI group reflects the
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clinical issues in the old age group with AMI; namely, presenting complaints tend to be atypical and ECG findings tend to be nondiagnostic. A frequent ECG finding is ST segment depression with the development of non-Q-wave infarct (13). As confirmed by this report, these “atypical” features (for young patients!) do not connote a lower mortality rate in the elderly. We must improve our recognition of the clinical presentation of AMI in the elderly; “atypical” presentations in reference to symptoms and ECG findings should be considered frequent and the norm. The clear message from the work of Shlipak et al. (8) is the need to lower the diagnostic threshold for considering AMI when LBBB is present, especially in the older patient. Can AMI be diagnosed by ECG when LBBB is present? Better tests for AMI that can be immediately available in the emergency department are being intensively investigated but, in the near future, the 12-lead ECG will remain the primary diagnostic tool to assess the presence of epicardial coronary arterial thrombosis and make the decision for reperfusion therapy. With LBBB, the course of ventricular activation is altered, which secondarily affects ventricular repolarization. The QRS, ST-segment and T wave of the ECG are always affected by LBBB. More often than not, the early signs of AMI will be obscured by the changes due to the conduction abnormality. The prevalence of LBBB and other cardiac conduction abnormalities increases with age. While LBBB due to “sclerodegenerative” disease (14 –16) or senile amyloidosis (17) can occur in the absence of other structural heart disease or cardiac symptoms (18), detailed clinicopathologic studies (14 – 17) show that LBBB increases in the elderly and is more often associated with advanced cardiac disease of several types. Thus, LBBB is a marker both of age and severe heart disease but not exclusively coronary disease. Multiple studies have evaluated the ability to diagnose AMI when LBBB is present (19 –24). The work of Sgarbossa et al. (24) is instructive in this regard. They developed diagnostic criteria for AMI when LBBB was present using data from the GUSTO-1 Trial (the derivation or training sample) and from a control population with LBBB and stable ischemic heart disease (the validation sample). Three ECG criteria based on ST segment displacement were found to have independent diagnostic value (see legend of the Fig. 1). The three criteria were assigned index scores and incorporated in a diagnostic algorithm. This algorithm was found to have a sensitivity of 78% and a specificity of 90% in the derivation/training sample. The diagnostic specificity remained high, 96%, but the sensitivity was quite low, 36%, when applied to the validation sample, a small group of 45 patients. In an earlier report, Shlipak et al. (25) tested the Sgarbossa algorithm and other ECG criteria for myocardial infarctions in patients with LBBB and found that none effectively distinguished the patients with myocardial infarction from those with other diagnoses. A possible explanation for these differing results is that the Sgarbossa algo-
JACC Vol. 36, No. 3, 2000 September 2000:713–6
rithm was derived and validated in a cohort of patients with LBBB from the GUSTO-1 Trial, which represented only 0.5% of the 26,003 patients enrolled in the trial (26). This low percentage of LBBB in AMI suggests that the cohort studied by Sgarbossa et al. (24) was highly selected and may not be representative of the universe of patients with this combination of abnormalities. The reported studies of LBBB-AMI suggest that an unknown, albeit small, subset of patients have ECG changes that are indicative of AMI and in this group these findings could lead to immediate fibrinolytic therapy. More research is needed to confirm, refine and determine the frequency of ECG findings of LBBB that may indicate AMI. For example, included in such studies would be the evaluation of serial ECGs, taken over a brief period of 30 to 40 min, to determine if fluctuating repolarization changes may enhance the sensitivity of the 12-lead ECG since repolarization changes are dynamic during the early course of transmural myocardial infarction. What might be done to resolve this issue? No simple approach to resolution is feasible. What can be done immediately and what must be done in order to provide better care is to have a much lower threshold for the suspicion of AMI in all elderly patients with nonspecific cardiac complaints, particularly dyspnea, but with a wide variety of complaints, which are common in AMI in the elderly. When LBBB is present, the suspicion of AMI should be increased, efforts should be made to obtain previous ECGs and particular attention should be paid to subtle changes in repolarization, which will lead to more definitive tests. In patients in whom the suspicion of AMI is high, reperfusion therapy should be seriously considered because of the high mortality of AMI-LBBB in elderly patients. Obviously, a highly individualized approach is needed with careful consideration of the patient’s general health activity status and co-morbidity (26). If fibrinolytic therapy is selected, streptokinase has been demonstrated in all studies to have a lower risk of cerebral hemorrhage—the most dreaded complication of therapy—which increases in the elderly population (27,28). In addition, decision analysis using the GISSI-1 database has demonstrated fibrinolysis to be cost effective even when the probability of diagnosis of AMI is relatively low in elderly patients because the mortality is so high and the mortality benefit was great (33% to 29% reduction) (29). In patients with LBBB in whom the diagnosis is probable but not certain, emergency cardiac catheterization both for diagnosis and to plan management is justified. Achieving immediate reperfusion with a catheter-based intervention in this setting is almost certainly more effective than thrombolytic therapy and avoids the risk of central nervous system (CNS) hemorrhage. The NRMI-2 registry emphasizes the approach that could be utilized to clarify the problem. Registries are powerful tools to assess these issues. A large registry of patients with LBBB who are evaluated in
JACC Vol. 36, No. 3, 2000 September 2000:713–6
Figure 1. The Venn diagram depicts the universe of patients with LBBB evaluated in the emergency department and the relationships between LBBB and AMI. Categories/subsets emphasize the wide range of possibilities that exist. The Venn diagram is discussed in the text. The LBBB with new ST displacement subset emphasizes there may be ECG changes helpful in diagnosing AMI. The scoring system of Sgarbossa is one approach. ST-segment elevation ⬎1 mm and concordant with QRS complex, 5 points; ST-segment depression ⬎1 mm in lead V1, V2, and V3, 3 points; ST-segment elevation ⬎5 mm and discordant with QRS complex, 2 points; an ECG score of 3 is used to diagnose AMI; 2 is suspicious for AMI.
emergency departments with a variety of complaints could constitute the study sample. The protocol for such a study would include clinical presentation, ECG findings (particularly study of serial ECGs) and the management selected, as well as outcomes. As in any good registry study, definitions would have to be agreed on and used in a prescriptive fashion. The Venn diagram (Fig. 1) provides a framework to discuss the multiple facets of the problem and management approaches. It is not intended to be prescriptive but to emphasize the fact that multiple permutations exist that call for fastidiously collected data to better define management strategies. If the Sgarbossa criteria were confirmed, patients in subsets A, B and C would proceed to revascularization. Subsets D, E and F pose the dilemma emphasized in the current Shlipak et al. (8) article. Patients in the D subgroup were more likely (13.2%) than patients in the E subgroup (2.6%) to receive reperfusion therapy, but both sets had unacceptably low attempts at reperfusion. Patients in the F subset would represent those with AMI who had confusing symptoms that were primarily not cardiac, such as fatigue, “generally not well,” CNS manifestations, among others— presentations that are common in elderly patients with AMI. Subset G represents patients who have an acute coronary syndrome without myocardial necrosis but who require energetic workup and care to prevent AMI. Subset H includes a highly problematic group of patients, some of whom would have acute coronary syndromes. The remaining LBBB patients (large circle) will represent a wide array of clinical entities including stable or unstable coronary syndromes. Since LBBB patients as a group are older, co-morbidity
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and frailty will be deterrents to aggressive evaluations and workup. However, in the absence of contraindications, urgent coronary arteriography would provide the pathway to better treatment in many patients. Although the use of arteriography in the elderly is increasing (30,31), currently in the U.S. the procedure is used more frequently in young, low-risk patients with AMI in whom the benefit will not be great (32,33). Acute myocardial infarction in the elderly with associated frailty and co-morbidity will always require highly individualized, thoughtful clinical judgment. The heterogeneity of the elderly and the heterogeneity of the emergency department patients with LBBB assure that randomized control trials will contribute little to the resolution of these problems (34). A carefully conceived registry study, as the current NRMI-2 study illustrates, can be an effective approach utilizing the scheme outlined in the Venn diagram (35). Shlipak et al. (8) have provided valuable information on an important problem, LBBB in patients with AMI, with their analysis of the extraordinary NRMI-2 database of ⬎29,000 patients. By focusing attention on the current management of this problematic group of patients, they expose a much larger problem in cardiology practice; namely the gross underutilization of reperfusion therapy in the elderly population with AMI. In this high-risk population, not only are better ECG criteria and other diagnostic approaches needed to diagnose AMI in the emergency department, but it is reasonable to use emergent coronary arteriography more frequently for diagnosis and to plan management. Since randomized control trials will not be done in the elderly, the registry method should be used and could help unravel difficult management problems. With ⬎70 million baby boomers soon to enter old age, the issues brought into focus by Shlipak et al. (8) and commented on in this editorial will become even more pressing. Addendum. A recent publication, (Thieman DR, Coresh J, Schulman S, et. al. Lack of benefit of intravenous thrombolysis in patients with myocardial infarction who are older than 75 years, Circulation 2000;101:2239 –2246 2000) reports the lack of benefit and potential adverse effects of fibrinolytic therapy in 7,864 Medicare patients, age 65 to 86 years, with the primary discharge diagnosis of acute myocardial infarction. This observational study needs to be confirmed but the data presented further emphasizes the complexities of the issues involved in elderly patients with acute myocardial infarction and makes catheter-based reperfusion procedures, as discussed in this editorial, more appealing. Reprint requests and correspondence: Dr. Gottlieb C. Friesinger II, Betty and Jack Bailey Professor of Cardiology, Vanderbilt University, Nashville, Tennessee 37232. E-mail: [email protected].
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REFERENCES 1. ISIS-2 Second International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction. ISIS-2. Lancet 1988;2:349 – 60. 2. GISSI-1. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;1:397– 402. 3. Bates ER. Revisiting reperfusion therapy in inferior myocardial infarction. J Am Coll Cardiol 1997;30:334 – 42. 4. Maggioni AP, Maseri A, Fresco C, et al. Age-related increase in mortality infarctions treated with thrombolysis. N Engl J Med 1993; 329:1331– 8. 5. Lee KL, Woodlief LH, Topol DJ, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction: results from an international trial of 41,021 patients. Circulation 1995;91:1659 – 68. 6. Goldberg RJ, Gore JM, Gurwitz JH, et al. The impact of age on the incidence and prognosis of initial myocardial infarction: the Worcester Heart Attack Study. Am Heart J 1989;117:543–9. 7. Weaver WD, Litwin PE, Martin JS, et al. Effect of age on use of thrombolytic therapy and mortality in acute myocardial infarction: the MITI Project Group. J Am Coll Cardiol 1991;18:657– 62. 8. Shlipak MG, Go AS, Frederick PD, et al. Treatment and outcomes of left bundle-branch block patients with myocardial infarction who present without chest pain. J Am Coll Cardiol 2000;36:706 –12. 9. Pathy MS. Clinical presentation of myocardial infection in the elderly. Br Heart J 1967;29:190 –9. 10. Nadelman J, Fishman WH, Ooi WL, et al. Prevalence, incidence and prognosis of recognized and unrecognized myocardial infarction in persons aged 75 years or older: the Bronx Aging Study, Am J Cardiol 1990;66:533–7. 11. Miller PF, Sheps DS, Bragdon EE, et al. Aging and pain perception in ischemic heart disease. Am Heart J 1990;120:22–30. 12. Sigurdsson E, Thorgeirsson G, Sigvaldason H, et al. Unrecognized myocardial infarction: epidemiology, clinical characteristics, and the prognostic role of angina pectoris: the Reykjavik Study. Ann Intern Med 1995;122:96 –102. 13. Krumholz HM, Friesinger GC, Cook EF, et al. Relationship of age with eligibility or thrombolytic therapy and mortality among patients with suspected acute myocardial infarction. J Am Geriatr Soc 1994; 42:127–31. 14. Lev M. The pathology of complete heart block. Prog Cardiovasc Dis 1964;6:317–26. 15. Lenegre J. Etiology and pathology of bilateral bundle branch clock in relation to complete heart block. Prog Cardiovasc Dis 1964;6:409 – 44. 16. Saguaro M, Horace K, Ohkawa S, Shimada H. A clinico-pathological study of the heart in the aged: the morphological classification of the 1,000 consecutive autopsy cases. Jpn Heart J 1975;16:526 –37. 17. Johansson B, Westermark P. Senile systemic amyloidosis: a clinicopathological study of twelve patients with massive amyloid infiltration. Int J Cardiol 1991;32:83–92.
JACC Vol. 36, No. 3, 2000 September 2000:713–6 18. Smith RF, Harthorne JW, Sanders CA. Acquired bundle branch block in a healthy population. Am Heart J 1970;80:746 –51. 19. Cabrera E, Friedland C. La onda de activacio´n ventricualr en el bloquero de rama izquierda con infarcto: un nuevo signo electrocardiogra´fico. Arch Inst Cardiol Mex 1953;23:441– 60. 20. Besoaı´n-Santander M, Go´mez-Ebensperguer G. Electrocardiographic diagnosis of myocardial infarction in cases of complete left bundle branch block. Am Heart J 1960;60:886 –97. 21. Doucet P, Walsh TJ, Massie E. A vectrocardiographic and electrocardiographic study of left bundle branch block with myocardial infarction. Am J Cardiol 1966;17:171–9. 22. Wackers FJ. The diagnosis of myocardial infarction in the presence of complete left bundle branch block. Cardiol Clin 1987;5:393– 401. 23. Hands ME, Cook EF, Stone PH, et al. Electrocardiographic diagnosis of myocardial infarction in the presence of complete left bundle branch block. Am Heart J 1988;116:23–31. 24. Sgarbossa EB, Pinski SL, Barbagelata A, et al. Electrocardiographic diagnosis of evolving acute myocardial infarction in the presence of left bundle-branch block. N Engl J Med 1996;334:481–7. 25. Shlipak MG, Lyons WL, Go AS, Chou TM, Evans GT, Browner WS. Should the electrocardiogram be used to guide therapy for patients with left bundle-branch block and suspected myocardial infarction? JAMA 1999;281:714 –9. 26. Welch HG, Albertsen PC, Nease RF, et al. Estimating treatment benefits for the elderly: the effect of competing risks. Ann Intern Med 1996;124:577. 27. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673– 82. 28. Simoons ML, Maggioni AP, Knatterud G, et al. Individual risk assessment for intracranial hermorrhage during thrombolytic therapy. Lancet 1995;342:1523– 8. 29. Krumholz HM, Pasternak RC, Weinstein MC, et al. Cost effectiveness of thrombolytic therapy with streptokinase in elderly patients with suspected acute myocardial infarction. N Engl J Med 1992;327:7–13. 30. Singh M, Mathew V, Garratt KN, et al. Effect of age on the outcome of angioplasty for acute myocardial infarction among patients treated at the Mayo Clinic. Am J Med 2000;108:187–92. 31. DeGeare VS, Grines CL. Primary percutaneous intervention in octogenarians with acute myocardial infarction: the treatment of choice. Am J Med 2000;108:257– 8. 32. Pilote L, Miller DP, Clift RM, et al. Determinants of the use of coronary arteriography and revascularization after thrombolysis for acute myocardial infarction. N Engl J Med 1996;335:1198 –1205. 33. Bates DW, Miller E, Bernstein S, et al. Coronary angiography and angioplasty after acute myocardial infarction. Ann Intern Med 1997; 126:539 –50. 34. Prabhat JHA, Deboer D, Sykora K, et al. Characteristics and mortality outcomes of thrombolysis trial participants and nonparticipants: a population-based comparison. J Am Coll Cardiol 1996;27:1335– 42. 35. Black N. Why we need observational studies to evaluate the effectiveness of health care. BMJ 1966;312:1215– 8.