Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome – Is There a Clinical Relevance?

<div><p>Objective</p><p>Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®.</p><p>Methodology, Results</p><p>A total of 24 patients (23 women, 1 man) with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA®); a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79%) had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis). Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003); the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029).</p><p>Conclusion</p><p>Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity to metals (mercury in particular) evaluated by LTT-MELISA®. We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients.</p></div

Comparison of a number of patients with positive stimulation index (SI ≥ 3) for individual metals between TS group and healthy controls.

<p>Comparison of a number of patients with positive stimulation index (SI ≥ 3) for individual metals between TS group and healthy controls.</p

Suggested hypothesis of pathological immune mechanisms in the Takotsubo syndrome.

<p>TS is associated with increased levels of catecholamines in the acute phase of this condition. Hypersensitivity reactions to environmental burden with metals, which are mediated by antigen/hapten-specific T-lymphocytes, were proved in 96% of our patients with Takotsubo syndrome. Chronic or acute hypersensitivity reactions are accompanied by an inflammatory reaction with the production of many cytokines and free radicals (i.e., an increased oxidative stress). The methionin-homocysteine cycle is one of the main endogenous antioxidant systems. At the same time, the methionine-homocysteine cycle provides methyl groups for the degradation of catecholamines, a process catalysed by catechol-O-methyltransferase (COMT). An “exhaustion” of the methionine-homocysteine cycle as a result of chronic oxidative stress can lead to a decreased degradation of catecholamines; in a subsequent stressful situation, which is generally characterised by an increased production of catecholamines, excessively high levels of catecholamines can occur, such as those typically found in TS patients. TS develops most frequently in postmenopausal women, who have decreased levels of sex hormones, particularly oestrogens. In general, oestrogens have a cardioprotective effect (by reducing the chronotropic and ionotropic effects of catecholamines); additionally, when taking into account the potential hypersensitivity, oestrogens also have anti-inflammatory effects. On top of that, progesterone–of which levels also decrease with age–has immunosuppressive effects.</p

Predictive accuracy of scoring models for rehospitalisation due to ADHF during a three-year follow-up period.

<p>Predictive accuracy of scoring models for rehospitalisation due to ADHF during a three-year follow-up period.</p

Landmark analyses of mortality after STEMI.

<p>Landmark analyses of mortality after STEMI.</p

Basic characteristics of the TS group and the control group of healthy individuals.

<p>Basic characteristics of the TS group and the control group of healthy individuals.</p

Overview of environmental burden with metals in the TS group and in the control group.

<p>Overview of environmental burden with metals in the TS group and in the control group.</p

Predictive accuracy of scoring models for mortality during a three-year follow-up period.

<p>Predictive accuracy of scoring models for mortality during a three-year follow-up period.</p

Risk-scoring models and their components.

<p>*Recurrent MI, stroke, major bleed, CHF/shock, arrhythmia, renal failure.</p><p>BP—blood pressure, LBBB—left bundle branch block; PCI—percutaneous coronary intervention.</p><p>Risk-scoring models and their components.</p

Baseline characteristics of patients and medical therapy upon hospital admission.

<p>*Recurrent MI, stroke, major bleed, CHF/shock, arrhythmia, renal failure;</p><p>MI—myocardial infarction, ACEI—angiotensin-converting enzyme inhibitor, ARB—angiotensin II receptor blockers, PCI—percutaneous coronary intervention, CABG—coronary artery bypass grafting, TIA—transient ischaemic attack, AHF—acute heart failure.</p><p>Baseline characteristics of patients and medical therapy upon hospital admission.</p