Growth Hormone, Acromegaly, and Heart Failure: An Intricate Triangulation

Luigi Saccà, Raffaele Napoli, Antonio Cittadini


Clin Endocrinol. 2003;59(6) 

In This Article

The Sides of the Triangle

GH and its tissue effector, IGF-I, exert profound effects on the cardiovascular system (Saccà et al., 1994). In longstanding acromegaly, cardiac performance progressively deteriorates because of structural and functional alterations of the myocardium - a condition referred to as acromegalic cardiomyopathy (Wright et al., 1970).

The development of cardiac disease in acromegaly is, in some respects, paradoxical and the underlying mechanisms are, in large part, still obscure. For several reasons. First, the relationship between GH and the heart has attracted interest only in recent years, when it became clear that GH and IGF-I play a role in the development, growth and function of the cardiovascular system (Saccà et al., 1994; Saccà & Fazio, 1996). Second, short-term exposure of the normal heart to high GH or IGF-I concentrations enhances myocardial contractility and relaxation (Cittadini et al., 1998, 1996). Furthermore, recent studies indicate that GH and IGF-I exert beneficial effects in a variety of experimental models of heart failure (Duerr et al., 1995; Yang et al., 1995; Cittadini et al., 1997; Houck et al., 1999; Tajima et al., 1999). In patients with dilated cardiomyopathy, GH was beneficial in some studies (Fazio et al., 1996; Volterrani et al., 1997; Genth-Zotz et al., 1999; Spallarossa et al., 1999), but not in others (Isgaard et al., 1998; Osterziel et al., 1998). In no instance, however, did GH impair cardiac function. Third, in animal models of IGF-I overexpression, left ventricular (LV) remodelling and dysfunction following myocardial ischaemia are attenuated rather than aggravated by IGF-I excess (Li et al., 1997). When myocardial infarction was induced in a rat model of pure GH deficiency, LV remodelling and function were severely compromised (Cittadini et al., 2001). Similarly, the consequences of acute myocardial infarction in humans were more severe in patients with low IGF-I levels in the immediate postinfarction period (Lee et al., 1999b). Collectively, the data point to a protective effect of the GH/IGF-I axis against progression of ischaemic injury towards heart dysfunction and failure.

These findings raise several crucial questions. A very basic one is: why is acromegaly a condition predisposing to heart failure if the direct effects of GH/IGF-I on the heart are all but detrimental? Another relevant question is whether the classic mechanisms responsible for heart failure are operative in patients with acromegaly. The concept that acromegalic heart disease is directly linked to GH/IGF-I excess appears too simplistic and does not reflect the complexity of the interaction. That is why the triangulation is intricate, the three players being: (1) GH excess causes acromegaly; (2) acromegaly leads to cardiac disease; and (3) GH is beneficial in models of heart failure.

In the following, an effort will be made: (1) to review the main changes occurring in the acromegalic heart; (2) to examine the genuine effects of GH/IGF-I on cardiac morphology and function in physiology and in heart failure; and (3) to relate these effects to the putative mechanisms responsible for the development and progression of heart failure in general ( Table 1 ).