significantly higher than in control patients. This observation is consistent with the previously reported finding of circulating IgG hemagglutinating antibodies to PPD in 60 percent of patients with moderate and 80 percent of patients with far-advanced pulmonary tuberculosis of more than one year's duration. 7 It is thus more than likely that the increase in serum IgG levels in pulmonary tuberculosis reported in this issue is a reflection of the presence of antibodies directed against allergenic constituents of M tuberculosis rather than a non.specific response. The humoral IgG antibodies to M tuberculosis probably do not protect the human host against either active or recurrent infection because they appear at the height of the disease and disappear with clinical improvement. They seem to be produced as a direct consequence of the presence of large numbers of actively multiplying tubercle bacilli in the human lung parenchyma over a prolonged period of time-an epiphenomenon that has no apparent influence on the course of the disease. SamuelO. Freed11Uln, M.D.· Montreal o Director,
Division of Clinical Immunology and Allergy, Montreal General Hospital; Professor of Medicine, McGill University. REFERENCES
1 Freedman SO, Kongshavn PL: Immunobiology of tuberculin hypersensitivity. Chest 68: (Suppl)470, 1975 2 Johansson SGO, Bennich HH, Berg T: The clinical significance of IgE. In Shwartz RS (ed). Progress in Clinical Immunology (Vol. 1). New York, Grone and Stratton, 1972, p 157 3 Gleich GJ, Jacob GL: Immunoglobulin E antibodies to pollen account for high percentages of total immunoglobulin E protein. Science 190:1106, 1975 4 Patterson R, Roberts M: IgE and IgG antibodies against AspergiUus fumigatus in sera of patients with bronchopulmonary allergic aspergillosis. Int Arch Allergy Appl Immunol46:150, 1974 5 Jarrett E, Ferguson A: Effect of T cell depletion on the potentiated ragin response. Nature 250:420,1974 6 Okumura KO, Tada T: Regulation of homocytotropic antibody formation in the rat. IX. Further characterization of the antigen specific inhibitory homocytotropic antibody response. J ImmunoII12:783, 1974 7 Freedman SO, Dolovich J, Turcotte R, et al: Circulating IgG (7S) hemagglutinins in pulmonary tuberculosis. Am Rev Respir Dis 94:896, 1966
Nontransmural Myocardial Infarction Myocardial infarction unassociated with acute development of ST-segment elevation and Q waves has been thought until recently to be a relatively benign syndrome. Indeed, the incidence of
2 EDITORiAlS
power failure and other serious complications has been considered to be low, and chest pain is intermediate between the discomfort of angina pectoris and the severe precordial pain of transmural myocardial infarction. 1,,2 Recently accumulated clinical experience, however, paints a less optimistic picture for myocardial infarction accompanied only by changes of the ST segment and T wave on the electrocardiogram. 3-6 In a recent issue of Chest, Kossowsky et al 7 added further evidence that nontransmural infarction is not always a benign disorder. They described a group of 35 patients with enzymatically verified myocardial infarction and ECGs showing symmetrically inverted T waves, who had a high incidence of progression to transmural myocardial infarction. Furthermore, two (15 percent) of the 13 patients who developed transmural infarction died of pump failure, while none of the 22 patients without this complication did so. Current experience regarding the outcome of nontransmural myocardial infarction has varied somewhat in the hands of different investigators. In two recent reports, the incidence of arrhythmias and shock and the in-hospital mortality were similar in patients with nontransmural and transmural myocardial infarction, when the former had enzymatic curves suggestive of myocardial necrosis. 3,,6 Furthermore, electrical instability has been noted in a high percentage of patients with ST-segment and Twave changes, even in the presence of equivocal enzymatic alterations, whereas power failure has been found only in patients with significant enzymatic changes. 5 These results suggest that patients with severe but transient coronary ischemia are at risk for fatal arrhythmias, but that myocardial necrosis may be required for power failure to ensue. Another consideration is whether patients with predominant ST-segment depression on the ECG are separable on clinical grounds from those showing only symmetric T-wave inversions. Both patterns are classified as nontransmural myocardial infarction. The electrocardiographic pattern of ST-segment depression has been associated in some reports with a mortality similar to that encountered in patients with transmural myocardial infarction,4"s while patients with only T-wave inversion were found to have a benign in-hospital course. s The experience of Kossowsky et aI, 7 which deals with a group of patients described as showing only T-wave inversion, corroborates this clinical observation only for the group of patients who did not suffer an extension .to transmural infarction. These reports and the variable outcome that they describe emphasize the need for more careful clinical subcategorizaCHEST, 70: 1, JULY, 1976
non of patients with nontransmural infarction. Several- comments can be made regarding the Study of Kossowsky et al. 7 First, the relatively benign prognosis (in terms of death from pump failure) in the 22 patients who escaped infarct extension -is not unexpected. The clinical course of patients with myocardial infarction has been convincingly linked to the extent of ischemic damage to cardiac muscle, 9 and rises in enzymatic levels (a good indicator of infarct size) have been found to b~ higher in patients with transmural than nontransmural myocardial infarction. 3." Secondly, Kossowsky et al7 have identified nontransmural myocardial infarction as an intermediate step on the way to transmural myocardial infarction in some patients. It is already well recognized that the dividing line between transient ischemia with short-lived electrocardiographic changes and absent or minor enzymatic elevations,10 and nontr~nsmural infarction with longer-lasting electrocardiographic changes and definite enzymatic rises, is not always clear-cut, and a "stuttering" progression to infarction is commonly seen. It appears from the study of Kossowsky et al7 that a similar gradual progression from nontransmural to transmural infarction also occurs rather frequently; however, it is disappointing that their complicated and uncomplicated groups could not be differentiated on clinical grounds at the onset of illness. Thirdly, and finally, the article by Kossowsky et al 7 focuses upon an important subgroup of patients in which the efficacy of measures currently being evaluated for their ability to limit infarct size9 should be investigated, ie, those with nontransmural infarction which may eventually become transmural. Although a means of delineating this group prospectively is not yet available, the high incidence of transmural extension in the study by Kossowsky et al7 Suggests that a controlled trial of therapy for intervention in all patients with nontransmural infarction might represent a profitable approach. One can only concur with Kossowsky and associates7 that· therapeutic manipulations may be more useful in the patient with a small nontransmural infarction than in the patient who has suffered massive transmural necrosis.
John E. Madi&, M.D.·
and William B. Hood, Jr., M.D.··
Boston
• Director, Coronary Care Unit, Boston City Hospital; and Assistant Professor of Medicine, Boston University School of Medicine. ··Chief, Cardiology Division, Boston City Hospital; and Professor of Medicine, Boston University School of Medicine. Reprint requeBts: Dr. Madw, Cardiology Division, Boston City Hospital, Boston 02118
CHEST, 70: 1, JULY, 1976
REFERENCES 1 Norris RM, Brandt PWT, Caughey DE, et al: A new coronary prognostic index. Lancet 1:274-278, 1969 2 Pmitt RO, Klakeg CH, Chapin LE: Certain clinical states and pathologic changes associated with deeply inverted T waves in the precordial electrocardiogram. Circulation 11:517-530, 1955 3 Madias JE, Chahine RA, Gorlin R, et al: A comparison of transmural and nont:rammural acute myocardial infarction. Circulation 49:498-502, 1974 4 Rigo P, Murray M, Taylor DR, et al: Hemodynamic and prognostic findings in patients with transmural and nontransmural infarction. Circulation 51:1064-1070, 1975 5 Abbott JA, Scheinman MM: Nondiagnostic electrocardiogram in patients with acute myocardial infarction: Clinical and anatomic correlations. Am J Med 55:608-613, 1973 6 Scheinman MM, Abbott JA: Clinical significance of transmural versus nontransmural electrocardiographic changes in patients with acute myocardial infarction. Am J Med 55:602-607, 1973 7 Kossowsky W A, Mohr BD, Ra&i S, et al: Superimposition of transmural infarction following acute subendocardial infarction: How frequent? Chest 69:758-761, 1976 8 Lown B, Vassaux C, Hood WB, et al: Unresolved problems in coronary care. Am J CardioI20:494-508, 1967 9 Braunwald E, Maroko PR: The reduction of infarct size: An idea whose time (for testing) has come. Circulation 50:206-209, 1974 10 Fischl SJ, Herman MY, Corlin R: The intermediate coronary syndrome: Clinical, angiographic and therapeutic aspects. N Eng} J Med 288:1193-1198, 1973
Atrial Fibrillation in Acute Myocardial Infarction Significance and Therapeutic Implications issue of Chest (see page 8), the importance I nofthisatrial fibrillation that develops during the course of acute myocardial infarction was again emphasized. 1 Considerable controversy continues to exist regarding the prognostic significance of atrial fibrillation during myocardial infarction. A number of investigators, including Dr. Cristal and his associates, have shown that there is a greater overall early mortality in those patients who develop abial fibrillation in this circumstance, especially in anterior infarction. Other authors!'! have shown that this complication is common but does not adversely affect mortality. A consideration of the possible mechanisms that produce atrial fibrillation in acute infarction and its hemodynamic consequences may provide a framework for resolving the controversy and for recommending 'appropriate therapy. The first mechanism considered by Cristal et al was the development of atrial fibrillation as a consequence of left ventricular failure, with an acute
EDITORIALS 3
Division of Clinical Immunology and Allergy, Montreal General Hospital; Professor of Medicine, McGill University. REFERENCES
1 Freedman SO, Kongshavn PL: Immunobiology of tuberculin hypersensitivity. Chest 68: (Suppl)470, 1975 2 Johansson SGO, Bennich HH, Berg T: The clinical significance of IgE. In Shwartz RS (ed). Progress in Clinical Immunology (Vol. 1). New York, Grone and Stratton, 1972, p 157 3 Gleich GJ, Jacob GL: Immunoglobulin E antibodies to pollen account for high percentages of total immunoglobulin E protein. Science 190:1106, 1975 4 Patterson R, Roberts M: IgE and IgG antibodies against AspergiUus fumigatus in sera of patients with bronchopulmonary allergic aspergillosis. Int Arch Allergy Appl Immunol46:150, 1974 5 Jarrett E, Ferguson A: Effect of T cell depletion on the potentiated ragin response. Nature 250:420,1974 6 Okumura KO, Tada T: Regulation of homocytotropic antibody formation in the rat. IX. Further characterization of the antigen specific inhibitory homocytotropic antibody response. J ImmunoII12:783, 1974 7 Freedman SO, Dolovich J, Turcotte R, et al: Circulating IgG (7S) hemagglutinins in pulmonary tuberculosis. Am Rev Respir Dis 94:896, 1966
Nontransmural Myocardial Infarction Myocardial infarction unassociated with acute development of ST-segment elevation and Q waves has been thought until recently to be a relatively benign syndrome. Indeed, the incidence of
2 EDITORiAlS
power failure and other serious complications has been considered to be low, and chest pain is intermediate between the discomfort of angina pectoris and the severe precordial pain of transmural myocardial infarction. 1,,2 Recently accumulated clinical experience, however, paints a less optimistic picture for myocardial infarction accompanied only by changes of the ST segment and T wave on the electrocardiogram. 3-6 In a recent issue of Chest, Kossowsky et al 7 added further evidence that nontransmural infarction is not always a benign disorder. They described a group of 35 patients with enzymatically verified myocardial infarction and ECGs showing symmetrically inverted T waves, who had a high incidence of progression to transmural myocardial infarction. Furthermore, two (15 percent) of the 13 patients who developed transmural infarction died of pump failure, while none of the 22 patients without this complication did so. Current experience regarding the outcome of nontransmural myocardial infarction has varied somewhat in the hands of different investigators. In two recent reports, the incidence of arrhythmias and shock and the in-hospital mortality were similar in patients with nontransmural and transmural myocardial infarction, when the former had enzymatic curves suggestive of myocardial necrosis. 3,,6 Furthermore, electrical instability has been noted in a high percentage of patients with ST-segment and Twave changes, even in the presence of equivocal enzymatic alterations, whereas power failure has been found only in patients with significant enzymatic changes. 5 These results suggest that patients with severe but transient coronary ischemia are at risk for fatal arrhythmias, but that myocardial necrosis may be required for power failure to ensue. Another consideration is whether patients with predominant ST-segment depression on the ECG are separable on clinical grounds from those showing only symmetric T-wave inversions. Both patterns are classified as nontransmural myocardial infarction. The electrocardiographic pattern of ST-segment depression has been associated in some reports with a mortality similar to that encountered in patients with transmural myocardial infarction,4"s while patients with only T-wave inversion were found to have a benign in-hospital course. s The experience of Kossowsky et aI, 7 which deals with a group of patients described as showing only T-wave inversion, corroborates this clinical observation only for the group of patients who did not suffer an extension .to transmural infarction. These reports and the variable outcome that they describe emphasize the need for more careful clinical subcategorizaCHEST, 70: 1, JULY, 1976
non of patients with nontransmural infarction. Several- comments can be made regarding the Study of Kossowsky et al. 7 First, the relatively benign prognosis (in terms of death from pump failure) in the 22 patients who escaped infarct extension -is not unexpected. The clinical course of patients with myocardial infarction has been convincingly linked to the extent of ischemic damage to cardiac muscle, 9 and rises in enzymatic levels (a good indicator of infarct size) have been found to b~ higher in patients with transmural than nontransmural myocardial infarction. 3." Secondly, Kossowsky et al7 have identified nontransmural myocardial infarction as an intermediate step on the way to transmural myocardial infarction in some patients. It is already well recognized that the dividing line between transient ischemia with short-lived electrocardiographic changes and absent or minor enzymatic elevations,10 and nontr~nsmural infarction with longer-lasting electrocardiographic changes and definite enzymatic rises, is not always clear-cut, and a "stuttering" progression to infarction is commonly seen. It appears from the study of Kossowsky et al7 that a similar gradual progression from nontransmural to transmural infarction also occurs rather frequently; however, it is disappointing that their complicated and uncomplicated groups could not be differentiated on clinical grounds at the onset of illness. Thirdly, and finally, the article by Kossowsky et al 7 focuses upon an important subgroup of patients in which the efficacy of measures currently being evaluated for their ability to limit infarct size9 should be investigated, ie, those with nontransmural infarction which may eventually become transmural. Although a means of delineating this group prospectively is not yet available, the high incidence of transmural extension in the study by Kossowsky et al7 Suggests that a controlled trial of therapy for intervention in all patients with nontransmural infarction might represent a profitable approach. One can only concur with Kossowsky and associates7 that· therapeutic manipulations may be more useful in the patient with a small nontransmural infarction than in the patient who has suffered massive transmural necrosis.
John E. Madi&, M.D.·
and William B. Hood, Jr., M.D.··
Boston
• Director, Coronary Care Unit, Boston City Hospital; and Assistant Professor of Medicine, Boston University School of Medicine. ··Chief, Cardiology Division, Boston City Hospital; and Professor of Medicine, Boston University School of Medicine. Reprint requeBts: Dr. Madw, Cardiology Division, Boston City Hospital, Boston 02118
CHEST, 70: 1, JULY, 1976
REFERENCES 1 Norris RM, Brandt PWT, Caughey DE, et al: A new coronary prognostic index. Lancet 1:274-278, 1969 2 Pmitt RO, Klakeg CH, Chapin LE: Certain clinical states and pathologic changes associated with deeply inverted T waves in the precordial electrocardiogram. Circulation 11:517-530, 1955 3 Madias JE, Chahine RA, Gorlin R, et al: A comparison of transmural and nont:rammural acute myocardial infarction. Circulation 49:498-502, 1974 4 Rigo P, Murray M, Taylor DR, et al: Hemodynamic and prognostic findings in patients with transmural and nontransmural infarction. Circulation 51:1064-1070, 1975 5 Abbott JA, Scheinman MM: Nondiagnostic electrocardiogram in patients with acute myocardial infarction: Clinical and anatomic correlations. Am J Med 55:608-613, 1973 6 Scheinman MM, Abbott JA: Clinical significance of transmural versus nontransmural electrocardiographic changes in patients with acute myocardial infarction. Am J Med 55:602-607, 1973 7 Kossowsky W A, Mohr BD, Ra&i S, et al: Superimposition of transmural infarction following acute subendocardial infarction: How frequent? Chest 69:758-761, 1976 8 Lown B, Vassaux C, Hood WB, et al: Unresolved problems in coronary care. Am J CardioI20:494-508, 1967 9 Braunwald E, Maroko PR: The reduction of infarct size: An idea whose time (for testing) has come. Circulation 50:206-209, 1974 10 Fischl SJ, Herman MY, Corlin R: The intermediate coronary syndrome: Clinical, angiographic and therapeutic aspects. N Eng} J Med 288:1193-1198, 1973
Atrial Fibrillation in Acute Myocardial Infarction Significance and Therapeutic Implications issue of Chest (see page 8), the importance I nofthisatrial fibrillation that develops during the course of acute myocardial infarction was again emphasized. 1 Considerable controversy continues to exist regarding the prognostic significance of atrial fibrillation during myocardial infarction. A number of investigators, including Dr. Cristal and his associates, have shown that there is a greater overall early mortality in those patients who develop abial fibrillation in this circumstance, especially in anterior infarction. Other authors!'! have shown that this complication is common but does not adversely affect mortality. A consideration of the possible mechanisms that produce atrial fibrillation in acute infarction and its hemodynamic consequences may provide a framework for resolving the controversy and for recommending 'appropriate therapy. The first mechanism considered by Cristal et al was the development of atrial fibrillation as a consequence of left ventricular failure, with an acute
EDITORIALS 3
