Corticotropin (ACTH) in heart disease: its paradoxical effect on sodium excretion in resistant congestive failure.

Since the spring of 1952 we have undertaken a clinical trial of corticotropin in 21 cardiac patients with resistant edema. Of these, there were eight with arteriosclerotic, eight with chronic rheumatic, and three with hypertensive heart disease, while two had cor pulmonale. Beneficial results were obtained in 17, or 81 per cent of the cases. These consisted of a spontaneous diuresis either during corticotropin administration or after its withdrawal, or an alteration of response to mercurials, the patients subsequently responding favorably, whereas they had previously been completely refrac-tory to the mercurial diuretics. D URING recent years, it has been increasingly realized that a number of edematous patients fail to respond to the usual diuretic measures now in use. The picture of truly resistant edema where diuretic measures, including vigorous use of mercurial diuretics, are entirely of no avail, or cause natriuresis with no weight loss (or even a weight gain), resulting inevitably in hypo-natremia, is a frustrating one. An occasional patient responds, albeit temporarily, to simultaneous administration of salt solution and a mercurial diuretic. Since the spring of 1952, we have obtained sufficient clinical evidence and electrolyte balance data which promise to establish cortico-tropin (ACTH) as the therapeutic agent par excellence for the situation just described. This is the more fascinating if one recalls that to date corticotropin has been considered contra-indicated in congestive heart failure due to its sodium-retaining effect. Well aware of its known physiologic actions at the time, we nonetheless decided to start a clinical trial of cortico-tropin in the following categories of patients in whom there was little to lose: (1) those cardiac patients with truly resistant edema as described above, (2) heart patients with severe myocardial insufficiency (left ventricular) in whom there was severe pulmonary passive congestion and incapacitating, unrelievable paroxysms of dyspnea and (3) cardiac patients with severe, associated intrinsic broncho-pulmonary disease (asthma, bronchiectasis, emphysema). The initial trial of corticotropin in these cardiac patients was guided by the consideration that benefit might be obtained from the action of the hormone on some organ-system of the body which would offset that concerned with sodium retention through increased production of desoxycorticosterone-like substances by the adrenal cortices. This might possibly be in the form of improvement of the myocardium. With this thought, the clinical trial of corti-cotropin in heart disease was launched, but not without fear and trepidation.