Prognostic impact of subclinical thyroid dysfunction in heart failure
Introduction
Heart failure is a frequent clinical syndrome representing the common final pathway of various heart diseases of different etiology [1], [2]. It has been acknowledged that comorbidities are important modifiers of disease progression and outcome in heart failure [3], [4]. Thyroid dysfunction represents a frequent comorbid condition exhibiting heterogeneous clinical manifestations [5], [6].
Both overt hyper- and hypothyroidism are known to profoundly impact on cardiac function. Tachycardia is the dominant clinical feature and pathophysiological force driving heart failure in patients with Grave's disease (autoimmune hyperthyroidism) and thyroid autonomy [7], [8], [9]. Low thyroid hormone levels were shown to reduce cardiac contractility and output by various mechanisms [5], [10]. Correspondingly, bradycardia and left ventricular heart failure are common in overt hypothyroidism [11]. The euthyroid sick syndrome (ESS) is defined by low levels of circulating triiodothyronine (T3) in patients with normal or slightly decreased thyroid stimulating hormone (TSH) and tetraiodothyronine (T4) concentrations and viewed as adaptive response to serious clinical impairment rather than genuine thyroid disease. Comorbid ESS in patients with heart failure has been reported to indicate a particularly grave prognosis [12].
Subclinical thyroid dysfunction is characterized by altered TSH but normal thyroid hormone levels. With a prevalence of up to 20% of the normal population aged 60–80 years it is much more frequent than overt thyroid dysfunction [13], [14]. There is an ongoing debate whether or not subclinical thyroid diseases are really clinically inapparent or whether they possess prognostic relevance [14], [15], [16], [17].
Several studies investigated the prognostic impact of subclinical thyroid dysfunction in heart disease. However, the data are inconclusive and partly conflicting [15], [18], [19]. One major limitation comparing studies on the association between thyroid function and clinical outcome in patients with cardiac disease is that selection of populations and definitions of thyroid disorders were heterogeneous, with several studies using only TSH as an indicator of thyroid dysfunction [4], [16], [17], [19], [20], [21]. It has, thus, remained unclear whether subclinical thyroid dysfunction is a clinically and prognostically relevant entity in heart failure requiring specific diagnostic and therapeutic measures.
We, therefore, investigated whether
- (i)
Subclinical thyroid dysfunction has an impact on overall survival in systolic heart failure;
- (ii)
The full thyroid profile including free T3 (fT3) and free T4 (fT4), in comparison to TSH only, confers better differential appraisal of thyroid function and, hence, incremental prognostic relevance;
- (iii)
Repeating thyroid function tests after 6 months improves the diagnostic and prognostic accuracy of these measurements.
Section snippets
Patients
Between March 2004 and December 2008, 1032 patients hospitalized for heart failure were included in the Interdisciplinary Network Heart Failure study (INH study). The original study investigated in 715 patients the effects of a telephone-based nurse intervention on clinical outcome and enrolled consecutive adults hospitalized for decompensated cardiac failure at nine hospitals in South Germany. Details of the study design have been reported elsewhere [22]. In brief, inclusion criteria were left
Baseline characteristics
Of the 1032 patients included in the INH study, 274 patients had to be excluded for incomplete (n = 176) or implausible (n = 9) results of thyroid tests or the intake of amiodarone, thyreostatic agents or corticosteroids (Fig. 1). Baseline characteristics of the remaining 758 patients (mean age 68 ± 12 years; range: 20–95 years; 29% female) are presented in Table 1. No differences were found regarding most baseline characteristics between patients with euthyroidism (n = 628), subclinical hyperthyroidism
Discussion
This prospective follow-up study in 758 well-characterized patients demonstrated that neither subclinical hyper- nor hypothyroidism are relevant prognostic factors in patients with systolic heart failure and ejection fraction ≤ 40%. Whereas in unadjusted analyses suppressed TSH alone and subclinical hyperthyroidism were associated with an increased risk of all-cause death by 35% and 44%, respectively, these associations were lost after adjustment for age. Using the full information on thyroid
Funding
This work was supported by:
Main sponsor: Federal Ministry of Education and Research, Germany [01GL0304].
Additional support: German Competence Network Heart Failure [01GI0205] and Comprehensive Heart Failure Center Würzburg [01EO1004].
None of the funding sources interfered with the collection, management, and interpretation of the data, nor requested review of the manuscript.
Acknowledgment
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
References (38)
- et al.
Epidemiology and cost of advanced heart failure
Prog Cardiovasc Dis
(2011) - et al.
Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: a meta-analysis
Int J Cardiol
(2008) - et al.
Altered thyroid hormone metabolism in advanced heart failure
J Am Coll Cardiol
(1990) - et al.
Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis
Am J Med
(2006) - et al.
Esc guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM)
Eur Heart J
(2008) - et al.
Biomarkers in advanced heart failure: diagnostic and therapeutic insights
Congest Heart Fail
(2011) - et al.
Clinical characteristics and major comorbidities in heart failure patients more than 85 years of age compared with younger age groups
Eur J Heart Fail
(2011) - et al.
Thyroid hormone and heart failure
Curr Heart Fail Rep
(2006) - et al.
The role of thyroid hormone in the pathophysiology of heart failure: clinical evidence
Heart Fail Rev
(2010) - et al.
Thyroid storm with multiorgan failure
Thyroid
(2010)
Clinical practice. Graves' disease
N Engl J Med
Cardiovascular involvement in patients with different causes of hyperthyroidism
Nat Rev Endocrinol
Effect of thyroid hormone on the contractility of self-organized heart muscle
In Vitro Cell Dev Biol Anim
Noninvasive evaluation of cardiac function in hypothyroidism. Response to gradual thyroxine replacement
N Engl J Med
Thyroid hormone and coronary artery disease: from clinical correlations to prognostic implications
Clin Cardiol
The prevalence of undiagnosed thyroid disorders in a previously iodine-deficient area
Thyroid
Thyroid function and mortality in older men: a prospective study
J Clin Endocrinol Metab
Review: the association of thyroid dysfunction with all-cause and circulatory mortality: is there a causal relationship?
J Clin Endocrinol Metab
Subclinical thyroid dysfunction and the risk of heart failure in older persons at high cardiovascular risk
J Clin Endocrinol Metab
Cited by (58)
The roles of thyroidectomy in patients with amiodarone-induced thyrotoxicosis: A systematic review
2024, Current Problems in CardiologyRelation Between Thyroid Function and Mortality in Patients With Chronic Heart Failure
2021, American Journal of CardiologyPerioperative Low Tetraiodothyronine Levels and Adverse Outcomes After Heart Transplantation: A Retrospective, Observational Study
2020, Journal of Cardiothoracic and Vascular AnesthesiaRelation of Low Triiodothyronine Syndrome Associated With Aging and Malnutrition to Adverse Outcome in Patients With Acute Heart Failure
2020, American Journal of CardiologySubclinical thyroid dysfunction and cardiovascular consequences: An alarming wake-up call?
2020, Trends in Cardiovascular MedicineCitation Excerpt :On the other hand, another study showed that euthyroid sick syndrome, and not SHypo or SHyper, is an important indicator of a poor prognosis in HF. Specifically, among 758 patients hospitalized for systolic HF (LV ejection fraction ≤40%), with SHypo present in 103 (14%) patients, over 3 years, only patients with euthyroid sick syndrome (n = 13) had a 3-fold age-adjusted increased risk of death compared to euthyroid patients (P = 0.001), while neither SHypo or SHyper were associated with increased age-adjusted mortality risk [37]. A pooled analysis of individual participant data of 25,390 individuals from 6 prospective cohort studies (216,248 person-years of follow-up), with 2068 (8.1%) having SHypo and 648 (2.6%) SHyper, showed that risks of HF events were increased with both higher and lower TSH levels (p < 0.01) [38].
Heart failure, micronutrient profile, and its connection with thyroid dysfunction and nutritional status
2019, Clinical NutritionCitation Excerpt :The present study found prevalence of thyroid dysfunction among patients with HF at 8.3%. Another study on the same patients who did not use amiodarone reported prevalence of 14% [12]. Both values match the study by Pasqualettiet al. [28].