LETTERS TO THE EDITOR
discharged a t 2 weeks, and there is little justification for keeping t h e m longer t h a n 3 weeks. The importance of both our paper and t h a t of Bloch et al. is that, despite the fact t h a t several studies of early mobilization and discharge have been reported, these are the only two t h a t are truly randomized.
strated to accomplish considerable benefits without excessive risks. Antoine Bloch, MD Hbpital Cantonal Geneva, Switzerland Massachusetts General Hospital Boston, Massachusetts Henry Blackburn, MD, FACC University of Minnesota Minneapolis, Minnesota
Roman W. DeSanctis, MD, FACC Adolph M. Hutter, Jr., MD, FACC Massachusetts General Hospital Boston, Massachusetts References 1. Sloch A, Maede J-P, Haissly J-C, et ah Early mobilization after myocardial infarction. A controlled study. Am J Cardio134:152-157, 1974 2. Huller AM Jr, Sldel VW, Shine KI, el ah Early hospital discharge after myocardial infarction. N Engl J Med 288:1141-1143, 1973
REPLY
The study by H u t t e r et al. is an i m p o r t a n t randomized study. Our comment about their report was directed at the low proportion of all cases with acute myocardial infarctiofi included (15 vs. 75 percent in our study). The mortality rate before randomization was about the same in the two Series. In our study, patients Were not excluded because of medical illness necessitating a longer stay, thus lengthening somewhat the average hospital stay of the early mobilization group. The principal difference in the material of the two studies is the percentage of patients excluded because of complicated myocardial infarction (50 percent in the H u t t e r study vs. 15 percent in our study). This difference is partly related to the skewed nature of patients referred to the cardiac unit of the Massachusetts General Hospital, and partly due to the fact t h a t the Geneva definition of uncomplicated infarction was far less restrictive. In addition, in H u t t e r ' s study patients were randomly assigned into groups on the 6th hospital day, after exclusion of patients with ventricular fibrillation, ventricular tachycardia, asystole, second degree heart block or complete heart block; persistence of more than five ventricular premature beats per minute, multifocal ventricular premature beats or paired ventricular premature beats into the 5th day; continued requirement of any antiarrhythmic t h e r a p y into the 5th day; persistence of any evidence of congestive h e a r t failure into the 5th day; any hypotension requiring vasopressor agents; definite thromboembolic complications during the first 5 days; coronary pain persisting into the 5th day; occurrence of any acute episodes of infarction within the preceding 6 months. In contrast, in our study patients were randomly assigned into groups 24 to 48 hours after admission, and the only causes of exclusion were severe heart failure, cardiogenic shock, severe r h y t h m disturbances, severe thoracic pain or severe psychological problems. The study of H u t t e r et al. showed the benefit of early mobilization and early discharge after uncomplicated myocardial infarction. We d e m o n s t r a t e d t h a t this practice can be applied to the majority of patients a d m i t t e d for myocardial infarction in a nonreferral general hospital. Finally, we suspect t h a t both of our reports overemphasized somewhat the absence of statistically significant differences. However, due to relatively small sample size and number of events, the statistical power was not sufficient to establish t h a t there were absolutely no differences. But the thrust of these two truly randomized studies is t h a t wellplanned early mobilization is now unequivocally demon-
METHYLPREDNISOLONE IN ACUTE MYOCARDIAL INFARCTION
T h e study by Vyden et al. 1 requires some clarification. It appears from the experimental protocol t h a t the authors are treating not simple acute myocardial infarction, but cardiogenic shock (systolic blood pressure below 80 m m Hg, sustained for 30 minutes). 2 In their preparation, mean systemic vascular resistance was increased concomitantly with the drop in cardiac index. In this condition, it has long been known t h a t glucocorticosteroids reduce peripheral vasoconstriction, thereby increasing the stroke volume of the left ventricle. 3,4 In myocardial infarction without shock, methylprednisolone has not produced any hemodynamic changes. 5 Thus, t h e beneficial effect of glucocorticosteroids in acute myocardial infarction must be advocated on a basis other than hemodynamic, and the beneficial hemodynamic effects seen in these experiments probably cannot be extrapolated to the human situation for the reasons the authors themselves enumerate. Mario Feola, MD, FACC Department of Surgery Jefferson Medical College Philadelphia, Pennsylvania References 1. Vyden JK, Nagasawa K, Rabinowitz B, et al: Effects of methylprednisoloneadministration in acute myocardial infarction. Am J Cardiot 34:677-686, 1974 2. Agress CM, Rosenberg MJ, Jacobs HI, at al: Protracted shock in the closed-chest
dog following coronary embolization with graded microspheres. Am J Physiol 170: 536, 1952 3. Sambhi MP, Weil MH, Udhoji UN: Acute pharmacodynamic effect of glucocorticoids: cardiac output and related hemodynamic changes in normal subjects and patients in shock. Circulation 31:523, 1965 4, Diefzman RH, Ullehei RC: The treatment of cardiogenic shock. V. The use of corticosteroids in the treatment of cardiogenic shock. Am Heart J 75:274, 1968 5. Spath JA, Lane DL, Lefer AM: Protective action of methylprednisolone on the myocardium during experimental myocardial ischemia in the cat. Circ Res 35:44, 1974
REPLY
Feola states t h a t "mean systemic vascular resistance was increased concomitantly with the drop in cardiac index" when acute myocardial infarction was produced in our preparation and draws certain conclusions from this. However, mean systemic vascular resistance was not significantly increased with the production of infarction, changing from 5.71 • 0.46 to 6.88 ± 0.76 (t = 1.41), and thus the conclusions drawn are not valid. Most clinicians treating acute myocardial infarction would agree cardiogenic shock is accompanied by a marked fall in stroke work index coupled with a significant increase to abnormal levels in left ventricular end-diastolic pressure. However, in our preparation there was no change in left ventricular end-diastolic pressure of any significance
October 6, 1975
The American Journal of CARDIOLOGY
Volume 36
539
discharged a t 2 weeks, and there is little justification for keeping t h e m longer t h a n 3 weeks. The importance of both our paper and t h a t of Bloch et al. is that, despite the fact t h a t several studies of early mobilization and discharge have been reported, these are the only two t h a t are truly randomized.
strated to accomplish considerable benefits without excessive risks. Antoine Bloch, MD Hbpital Cantonal Geneva, Switzerland Massachusetts General Hospital Boston, Massachusetts Henry Blackburn, MD, FACC University of Minnesota Minneapolis, Minnesota
Roman W. DeSanctis, MD, FACC Adolph M. Hutter, Jr., MD, FACC Massachusetts General Hospital Boston, Massachusetts References 1. Sloch A, Maede J-P, Haissly J-C, et ah Early mobilization after myocardial infarction. A controlled study. Am J Cardio134:152-157, 1974 2. Huller AM Jr, Sldel VW, Shine KI, el ah Early hospital discharge after myocardial infarction. N Engl J Med 288:1141-1143, 1973
REPLY
The study by H u t t e r et al. is an i m p o r t a n t randomized study. Our comment about their report was directed at the low proportion of all cases with acute myocardial infarctiofi included (15 vs. 75 percent in our study). The mortality rate before randomization was about the same in the two Series. In our study, patients Were not excluded because of medical illness necessitating a longer stay, thus lengthening somewhat the average hospital stay of the early mobilization group. The principal difference in the material of the two studies is the percentage of patients excluded because of complicated myocardial infarction (50 percent in the H u t t e r study vs. 15 percent in our study). This difference is partly related to the skewed nature of patients referred to the cardiac unit of the Massachusetts General Hospital, and partly due to the fact t h a t the Geneva definition of uncomplicated infarction was far less restrictive. In addition, in H u t t e r ' s study patients were randomly assigned into groups on the 6th hospital day, after exclusion of patients with ventricular fibrillation, ventricular tachycardia, asystole, second degree heart block or complete heart block; persistence of more than five ventricular premature beats per minute, multifocal ventricular premature beats or paired ventricular premature beats into the 5th day; continued requirement of any antiarrhythmic t h e r a p y into the 5th day; persistence of any evidence of congestive h e a r t failure into the 5th day; any hypotension requiring vasopressor agents; definite thromboembolic complications during the first 5 days; coronary pain persisting into the 5th day; occurrence of any acute episodes of infarction within the preceding 6 months. In contrast, in our study patients were randomly assigned into groups 24 to 48 hours after admission, and the only causes of exclusion were severe heart failure, cardiogenic shock, severe r h y t h m disturbances, severe thoracic pain or severe psychological problems. The study of H u t t e r et al. showed the benefit of early mobilization and early discharge after uncomplicated myocardial infarction. We d e m o n s t r a t e d t h a t this practice can be applied to the majority of patients a d m i t t e d for myocardial infarction in a nonreferral general hospital. Finally, we suspect t h a t both of our reports overemphasized somewhat the absence of statistically significant differences. However, due to relatively small sample size and number of events, the statistical power was not sufficient to establish t h a t there were absolutely no differences. But the thrust of these two truly randomized studies is t h a t wellplanned early mobilization is now unequivocally demon-
METHYLPREDNISOLONE IN ACUTE MYOCARDIAL INFARCTION
T h e study by Vyden et al. 1 requires some clarification. It appears from the experimental protocol t h a t the authors are treating not simple acute myocardial infarction, but cardiogenic shock (systolic blood pressure below 80 m m Hg, sustained for 30 minutes). 2 In their preparation, mean systemic vascular resistance was increased concomitantly with the drop in cardiac index. In this condition, it has long been known t h a t glucocorticosteroids reduce peripheral vasoconstriction, thereby increasing the stroke volume of the left ventricle. 3,4 In myocardial infarction without shock, methylprednisolone has not produced any hemodynamic changes. 5 Thus, t h e beneficial effect of glucocorticosteroids in acute myocardial infarction must be advocated on a basis other than hemodynamic, and the beneficial hemodynamic effects seen in these experiments probably cannot be extrapolated to the human situation for the reasons the authors themselves enumerate. Mario Feola, MD, FACC Department of Surgery Jefferson Medical College Philadelphia, Pennsylvania References 1. Vyden JK, Nagasawa K, Rabinowitz B, et al: Effects of methylprednisoloneadministration in acute myocardial infarction. Am J Cardiot 34:677-686, 1974 2. Agress CM, Rosenberg MJ, Jacobs HI, at al: Protracted shock in the closed-chest
dog following coronary embolization with graded microspheres. Am J Physiol 170: 536, 1952 3. Sambhi MP, Weil MH, Udhoji UN: Acute pharmacodynamic effect of glucocorticoids: cardiac output and related hemodynamic changes in normal subjects and patients in shock. Circulation 31:523, 1965 4, Diefzman RH, Ullehei RC: The treatment of cardiogenic shock. V. The use of corticosteroids in the treatment of cardiogenic shock. Am Heart J 75:274, 1968 5. Spath JA, Lane DL, Lefer AM: Protective action of methylprednisolone on the myocardium during experimental myocardial ischemia in the cat. Circ Res 35:44, 1974
REPLY
Feola states t h a t "mean systemic vascular resistance was increased concomitantly with the drop in cardiac index" when acute myocardial infarction was produced in our preparation and draws certain conclusions from this. However, mean systemic vascular resistance was not significantly increased with the production of infarction, changing from 5.71 • 0.46 to 6.88 ± 0.76 (t = 1.41), and thus the conclusions drawn are not valid. Most clinicians treating acute myocardial infarction would agree cardiogenic shock is accompanied by a marked fall in stroke work index coupled with a significant increase to abnormal levels in left ventricular end-diastolic pressure. However, in our preparation there was no change in left ventricular end-diastolic pressure of any significance
October 6, 1975
The American Journal of CARDIOLOGY
Volume 36
539
