Plasma bio-adrenomedullin is a marker of acute heart failure severity in patients with acute coronary syndrome

Background: The assessment of acute heart failure (AHF) in patients with acute coronary syndrome (ACS) is challenging. This study tested whether measuring plasma adrenomedullin in patients admitted for ACS provides valuable information regarding the presence of AHF at admission or its occurrence during hospitalization. Methods and results: The study population consisted of 927 prospectively enrolled patients with ACS. Blood samples for the measurement of plasma bio-adrenomedullin (bio-ADM) were collected at admission. Patients with alveolar pulmonary edema and interstitial pulmonary edema on chest radiography at admission had stepwise higher plasma concentrations of bio-ADM compared to patients with no or mild pulmonary congestion: 54.3 ± 10.6 vs. 27.6 ± 2.1 vs. 22.5 ± 0.7 ng/L, overall P < 0.001. Patients with ACS complicated by AHF during the index hospitalization displayed higher plasma bio-ADM concentrations at admission compared to patients without AHF (33.8 ± 2.7 vs. 21.8 ± 0.7, P < 0.001): the higher the severity of AHF, the higher plasma bio-ADM concentrations at admission. Patients with cardiogenic shock displayed the highest values. Accordingly, bio-ADM concentrations at admission were associated with a higher risk of occurrence of AHF during index hospitalization (odds ratio 1.018, 95% confidence interval 1.011–1.026, P < 0.001). Conclusions: Plasma adrenomedullin is a marker associated with AHF severity in patients with ACS. Keywords: Bio-adrenomedullin, Acute coronary syndrome, Acute heart failure, Pulmonary edem

Plasma Levels of Soluble CD146 Reflect the Severity of Pulmonary Congestion Better Than Brain Natriuretic Peptide in Acute Coronary Syndrome

BACKGROUND: Acute heart failure negatively affects short-term outcomes of patients with acute coronary syndrome (ACS). Therefore, reliable and non-invasive assessment of pulmonary congestion is needed to select patients requiring more intensive monitoring and therapy. Since plasma levels of natriuretic peptides are influenced by myocardial ischemia, they might not reliably reflect congestion in the context of ACS. The novel endothelial biomarker, soluble CD146 (sCD146), presents discriminative power for detecting the cardiac origin of acute dyspnea similar to that of natriuretic peptides and is associated with systemic congestion. We evaluated the performance of sCD146 for the assessment of pulmonary congestion in the early phase of ACS. METHODS: One thousand twenty-one consecutive patients with ACS were prospectively enrolled. Plasma levels of sCD146, brain natriuretic peptide (BNP), and high-sensitive troponin T were measured within 24 hr after the onset of chest pain. Pulmonary congestion on chest radiography was determined and classified in three groups according to the degree of congestion. RESULTS: Nine hundred twenty-seven patients with ACS were analyzed. Ninety-two (10%) patients showed signs of pulmonary edema on chest radiography. Plasma levels of sCD146 reflected the radiological severity of pulmonary congestion. Higher plasma levels of sCD146 were associated with the worse degree of pulmonary congestion. In contrast to BNP, sCD146 levels were not affected by the level of troponin T. CONCLUSIONS: The novel endothelial biomarker, sCD146, correlates with radiological severity of pulmonary congestion in the early phase of ACS and, in contrast to BNP, is not affected by the amount of myocardial cell necrosis

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

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

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

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