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The concept that clinically euthyroid patients on T4 therapy
could have changes in cardiac function consistent with H is supported by
different studies. Eighteen hypo patients taking a mean T4 dose
of 150 µg/d (88) whose TSH levels were lower than 0.3 mU/l had a
reduced preejection period compared to controls. In another study (89),
hypo subjects treated with T4, having both normal free T4
and T3 concentrations but suppressed TSH levels, showed mild
but significant changes in myocardial function, thus reflecting "tissue
H" at the cardiac level. Furthermore, 20 subjects on suppressive doses
of T4 averaging 163±34 µg/d, had significant changes
in systolic time intervals including higher values of left ventricular
fractional shortening and rate-adjusted velocity of shortening (90). ECG
monitoring demonstrated significant increases in average heart rate in
the patients compared to controls. Indeed, the prevalence of atrial premature
beats was also higher in the patients compared to controls (100 vs 60%)
and one of the patients had spontaneous runs of AF. Furthermore, echocardiographic
analysis showed relevant diastolic dysfunction (91) and an increased left
ventricular mass index in patients compared to controls. Marked impairment
of cardiac functional reserve and physical exercise capacity were also
noted (92). Using a b1-selective antagonist for 3-6 months in association
with the T4 suppressive therapy, the same authors showed that
the heart rate normalised and the left ventricular mass was significantly
reduced towards normal (93). Interestingly, this therapy did not significantly
alter indices of cardiac contractility as fractional shortening and velocity
of circumferential fiber shortening. Importantly, the b-adrenergic blockade
also decreased atrial premature beats and eliminated the spontaneous AF
in the single patient where it occurred. Finally, this same study utilising
the H symptom rating scale score showed that b-blockade significantly improved
the patient' sense of "well- being" as well as cardiac performance and
exercise tolerance. In contrast, with the exception of an 18% increase
in left ventricular mass index in one study (94), two recent papers showed
that in patients with long-term TSH- suppressive therapy with T4,
indexes of systolic and diastolic function and interventricular septal
thickness were similar to control values (94, 95). Nevertheless, subclinical
H may have significant effects on cardiac structure and function. Most
of the T4-induced symptoms are reversed by b-adenergic blockade
therapy although cardiac contractility remains augmented. These studies
emphasise that T4 suppressive therapy has consequences, many
of which are clinically relevant. Thus, the clinical recommendation arising
from these findings is that patients on T4 therapy for replacement
should be dosed in such a way as to achieve a normal and not suppressed
TSH level. Furthermore, when T4 suppressive therapy is clinically
indicated, b-adrenergic blockade may be of great benefit.
Mild thyroid gland failure, evidenced solely by elevation of the serum TSH concentration, is associated with subtly decreased myocardial contractility. Ridgway et al. observed a modest but significant reduction in contractility, as assessed by non-invasive measurement of phonocardiographic systolic time intervals (96). Patients in this series had a substantially elevated mean serum TSH concentration (28 mU/l). In contrast, another study (97) failed to identify significant impairment of contractile function in patients with subclinical hypo in comparison with euthyroid controls or with their statuses following T4 therapy. In summary, current evidence suggests that subclinical hypo affects cardiac function and risk of atherosclerotic cardiovascular disease only when it is severe, and perhaps when it is superimposed on another underlying cardiac or metabolic disorder. |
