Low-T3 Syndrome. A strong prognostic predictor of death in patients with heart disease

Clinical and experimental evidences have shown the important role
of the endocrine function in the homeostasis of cardiovascular
system. In particular, triiodothyronine (T3), the biologically active
thyroid hormone, plays a critical role in modulating heart rate and
cardiac contractility as well as arterial peripheral resistances. A typical pattern of an altered thyroid hormone metabolism characterized by low-T3 circulating levels (Low -T3 syndrome) has been described in
patients with severe systemic disease. This Low-T3 syndrome has
commonly been interpreted by the medical community as an adaptive
compensatory and thus beneficial response that decreases energy
consumption in diseased states. This interpretation, however, has
recently been questioned. On the basis of that, in the 1999 we started
a prospective study aimed to assess the potential relation between
thyroid function and prognosis of patients with cardiac disease. From
the computerized patient-archive of the CNR Clinical Physiology
Institute of Pisa, 563 patients with several cardiac disorders, in whom
thyroid hormone assessment was done at the time of hospitalization,
were enrolled in the study. After the 1-year follow-up, cumulative
death (any natural death) and cardiac death were considered. An
early important result was the high incidence of the Low-T3
syndrome (33% of studied patients). Moreover, patients with low-T3
concentrations had significantly higher incidence of total and cardiac
death (14.3% vs 3%, p<0.0001 for total death; 7.5% vs 1.5% for
cardiac death, p<0.0001) (Fig.1). The prognostic effectiveness of the
T3 was more evident from the univariate and multivariate analysis
according to the Cox model and the logistic regression analysis. T3
was the most important independent predictor for cumulative death in
both the analyses, rather than the conventional prognostic cardiac
markers, i.e. ejection fraction (LVEF) and functional NYHA class, or
the well known cardiac risk factors (diabetes, hypercolesterolemia, obesity, etc) (Fig. 2). Moreover, we observed a
very good correlation between T3 blood levels and survival time; that
is the lower the T3 levels the lower the survival time
(Fig 3). Another important finding was the absence of any direct
correlation between T3 and LVEF. Consequently, it is very
likely that these 2 parameters are the expression of different aspects
of the disease evolving process, T3 being considered as a systemic
marker, strictly related to the "overall body" deterioration whereas the
LVEF more closely representing a "single organ" marker, i.e. of heart
The natural progresses of this research field are
clinical/therapeutical and physiological ones. We are setting a
multicentric study aimed to assess the prognostic impact of the
chronic treatment with oral T3 in patients with heart failure and Low-T3 syndrome. Moreover, patients with subclinical hypothyroidism, that
is with minimal hormonal alterations, and patients with heart failure
and Low-T3 syndrome are studied before and after oral T3 therapy
by using high-tech diagnostic tools (i.e. magnetic resonance).
The preliminary results are encouraging and seem to confirm the
critical role of thyroid hormones in the cardiovascular homeostasis.

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