Neurohumoral activation in congestive heart failure: A double‐edged sword?

The search for the basic mechanism(s) responsible for the progressive and frequently irreversible deterioration of left ventricular pump function in congestive heart failure has been quite extensive; nonetheless, no single explanation has been forthcoming. Indeed, given the complexity of this disease process, it is becoming increasingly unlikely that a single pathogenetic mechanism will ever be uncovered for congestive heart failure. This review will examine recent experimental and clinical evidence which suggests that excessive adrenergic stimulation of the heart is double‐edged. That is, while increased adrenergic input to the heart may initially enable the failing myocardium to function adequately for a period of months to years, continued excessive adrenergic stimulation of the heart through both local neural and circulating catecholamines may lead to frank myopathic effects on the heart, with resultant worsening of left ventricular function and the development of intractable congestive heart failure. While we do not mean to suggest that excessive sympathetic stimulation of the heart is the only, or even the major mechanism responsible for the development of irreversible congestive heart failure, the data reviewed herein do suggest that adrenergic stimulation may play a primary role in the pathogenesis of congestive heart failure.