Early descriptions of heart failure focused on the syndrome of congestion, an excess of the wet or melancholic humors, "dropsy,"
or "backward" failure. Focus on forward failure was sharpened by dramatic initial responses to agents that stimulate
contractility. More precise measurement of impaired contraction at the level of the heart and the myocyte itself later redefined
heart failure as a malady of impaired forward function. The inability to sustain early improvements in most with inotropic
agents in was accompanied by increased mortality in human studies.
While no veterinary studies have demonstrated similar adverse responses to positive inotropic therapy the focus of therapy
paralleling human medicine has shifted to mediating chronic response via inhibition of the renin-angiotensin system (RAAS)
and peripheral blockade of β-adrenergic receptors. While only RAAS modification has proven to decrease mortality in our patients,
β-adrenergic blockade is has been gaining interest as use of these drugs in chronic heart failure have been found over time
to help preserve and in some cases improve contractility, decrease filling pressures, and prolong survival. These neurohormonal
antagonists decrease the development and worsening of heart failure. The decision to add inotropic therapy has been controversial
in human medicine as most of these available drugs result in increase myocardial oxygen consumption hearts that may already
be deprived of oxygen secondary to myocardial infarction.
The decision to use inotropic therapy and the selection of inotropic agent should reflect the realistic goals of therapy for
the individual with heart failure. The diversity of goals and setting and the limited drugs available have limited the performance
of randomized controlled trials to establish evidence on which to base these therapies. Because of new drug classes available
for our patients; sharper focus on current practices and outcomes with inotropic therapy could direct efforts to design trials
for some situations and guide prospective data collection to advance our understanding of the best time to start utilizting
these drugs. Since majority of heart failure in veterinary patients is secondary to mitral valve disease, most of our patients
have preserved cardiac output at rest and are limited primarily by impaired volume regulation and diminished cardiac output
responses to excitement. Inotropic therapy is frequently considered in hopes that either brief or prolonged stimulation of
contractility to increase perfusion may help to restore compensation for a period of time. With myocardial failure (dilated
cardiomyopathy, end-stage mitral regurgitation), positive inotropes play an integral role. Positive inotropes may also have
a beneficial effect in early mitral regurgitation by reducing the severity of regurgitation through reduction in isovolumetric
contraction time and geometrical changes on the mitral annulus.
Digoxin is the most commonly used oral positive inotrope. The use of digoxin in heart failure has been debated for hundreds
of years. It is certainly recognized as a drug with beneficial effects but with a significant risk for toxicity. There is
no argument against its use with atrial fibrillation but some controversy still exists about its use with normal sinus rhythm.
With the development of a neuroendocrine approach to heart failure therapy, digoxin has experienced a renewed interest and
its use is on the rise (to be discussed under neuroendocrine-based therapy). In the author's opinion, digoxin is indicated
when moderate to severe congestive heart failure is present (component of "triple-therapy") and possibly earlier. Digoxin has been shown to improve baroreceptor function and reduce sympathetic tone. Given that digoxin is a weak positive inotrope
at best, the baroreceptor effect is now the primary indication for its use in heart failure aside from atrial fibrillation
therapy. Careful dosing and frequent monitoring of serum levels is necessary especially with concurrent drug therapy or when
reduced renal function is present.