endothelin-1 and Syncope

The early detection of cardiac syncope is challenging. We aimed to evaluate the diagnostic value of 4 novel prohormones, quantifying different neurohumoral pathways, possibly involved in the pathophysiological features of cardiac syncope: midregional-pro-A-type natriuretic peptide (MRproANP), C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin.. The use of MRproANP significantly improves the early detection of cardiac syncope among unselected patients presenting to the ED with syncope.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01548352.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Early Diagnosis; Emergency Service, Hospital; Endothelin-1; Female; Follow-Up Studies; Glycopeptides; Humans; Male; Middle Aged; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Protein Precursors; Syncope

The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.. An observational study was conducted including 255 patients (mean age 60 years, range 15-93; 45% men) with unexplained syncopal attacks. Subjects underwent an expanded head-up tilt test including carotid sinus massage, and nitroglycerin provocation if indicated. Using logistic regression, we explored the associations between specific diagnoses of syncope and resting levels of circulating biomarkers: C-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1 precursor fragment (CT-proET-1), midregional fragments of pro-atrial natriuretic peptide (MR-proANP) and pro-adrenomedullin (MR-proADM).. A total of 142 (56%) patients were diagnosed with vasovagal syncope (VVS), 85 (33%) with orthostatic hypotension (OH) and 47 (18%) with carotid sinus hypersensitivity (CSH); in addition, 74 (29%) patients had more than one diagnosis. Thirty-five patients (14%) demonstrated a cardioinhibitory reflex. The probability of VVS was highest in the first quartile of MR-proANP [Q1 vs. Q4: odds ratio (OR) 5.57, 95% confidence interval (CI) 1.86-16.74; P < 0.001] and CT-proET-1 (OR 7.17, 95% CI 2.43-21.13; P < 0.001). By contrast, the probability of OH was highest in the fourth quartile of CT-proET-1 (Q4 vs. Q1: OR 8.66, 95% CI 2.49-30.17; P < 0.001). Furthermore, CSH was most frequently observed in the first quartile of MR-proANP (Q1 vs. Q4: OR 6.57, 95% CI 1.62-26.62; P = 0.008) among those over 60 years of age, whereas the cardioinhibitory reflex was strongly associated with low CT-proET-1 levels (Q1 vs. Q4: OR 69.7, 95% CI 6.97-696.6; P < 0.001). Moreover, in patients with VVS, a high concentration of CT-proET-1 was predictive of OH (OR per 1 SD 2.4, 95% CI 1.15-5.02; P = 0.02), whereas low CT-proET-1 suggested involvement of the cardioinhibitory reflex (OR per 1SD 0.42, 95% CI 0.25-0.70; P = 0.001).. The levels of MR-proANP and CT-proET-1 are markedly changed in common forms of syncope, suggesting the involvement of novel neurohormonal mechanisms in syncopal attacks.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Electrocardiography; Endothelin-1; Female; Humans; Male; Middle Aged; Peptide Fragments; Retrospective Studies; Syncope; Vasopressins; Young Adult

Jugular venous reflux (JVR) has been reported to cause cough syncope via retrograde-transmitted venous hypertension and consequently decreased cerebral blood flow (CBF). Unmatched frequencies of JVR and cough syncope led us to postulate that there should be additional factors combined with JVR to exaggerate CBF decrement during cough, leading to syncope. The present pilot study tested the hypothesis that JVR, in addition to an increased level of plasma endothelin-1 (ET-1), a potent vasoconstrictor, is involved in the pathophysiology of cough syncope.. Seventeen patients with cough syncope or pre-syncope (Mean[SD] = 74.63(12.37) years; 15 males) and 51 age/gender-matched controls received color-coded duplex ultrasonography for JVR determination and plasma ET-1 level measurements.. Multivariate logistic analysis showed that the presence of both-side JVR (odds ratio [OR] = 10.77, 95% confident interval [CI] = 2.40-48.35, p = 0.0019) and plasma ET-1 > 3.43 pg/ml (OR = 14.57, 95% CI = 2.95-71.59, p = 0.001) were independently associated with the presence of cough syncope/ pre-syncope respectively. There was less incidence of cough syncope/ pre-syncope in subjects with the absence of both-side JVR and a plasma ET-1 ≦3.43 pg/ml. Presence of both side JVR and plasma ET-1 level of > 3.43 pg/ml, increased risk for cough syncope/pre-syncope (p < 0.001).. JVR and higher plasma levels of ET-1 are associated with cough syncope/ pre-syncope. Although sample size of this study was small, we showed a synergistic effect between JVR and plasma ET-1 levels on the occurrence of cough syncope/pre-syncope. Future studies should confirm our pilot findings.

Topics: Aged; Aged, 80 and over; Arterial Pressure; Case-Control Studies; Cerebrovascular Circulation; Cough; Echocardiography, Doppler, Color; Electrocardiography; Electroencephalography; Endothelin-1; Female; Humans; Jugular Veins; Male; Middle Aged; Pilot Projects; Statistics as Topic; Syncope

The endothelins are peptides with vasoconstricting and growth-promoting properties. Endothelin-1 (ET-1) is known with its direct positive inotropic and chronotropic effects on isolated heart and with growth effects. The aim of this pilot study was to investigate the frequency distribution of the common polymorphism of the ET-1 gene and its possible relation with hemodynamic consequences of malignant ventricular arrhythmias in patients with structural heart disease. We studied 26 consecutive patients with malignant ventricular arrhythmias and implantable cardioverterdefibrillators with a mean age of 62.7 +/- 12.2 years and a mean left ventricular ejection fraction of 0.37 +/- 11.0. Taq polymorphism of ET-1 was detected using our original polymerase chain reaction method. The polymerase chain reaction product with a length of 358 basepairs (bp) (primers 5'-CAA ACC GAT GTC CTC TGT A-3' and 5'-ACC AAA CAC ATT TCC CTA TT-3') in its non-mutated form contains a target sequence for TaqI restrictive enzyme, while a mutated product loses this cleavage site. Of 26 patients, nine (34%) had recurrent palpitations and eight (30.8%) had syncopes during their malignant arrhythmias. Nineteen patients were given amiodarone after implantable cardioverter-defibrillator insertion and seven were not treated with amiodarone. Fifteen patients had (++), 11 (+-) and 0 (- -) ET-1 genotype. The risk for syncopes was associated with the (++) genotype of the ET-1 gene (P = 0.01). Patients receiving amiodarone had significantly higher frequency of the (++) genotype (P = 0.011). All our results indicate that the presence of the ET-1 genotype (++) in patients with structural heart disease, severe left ventricular dysfunction and malignant ventricular arrhythmias increases the risk for these patients of hemodynamic collapse during these arrhythmias.

Topics: Aged; Amino Acid Sequence; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Defibrillators, Implantable; Endothelin-1; Female; Gene Frequency; Genetic Predisposition to Disease; Hemodynamics; Humans; Male; Middle Aged; Molecular Sequence Data; Phenotype; Pilot Projects; Polymorphism, Genetic; Recurrence; Risk Factors; Stroke Volume; Syncope; Time Factors; Treatment Outcome; Ventricular Function, Left

The neurohumoral events associated with neurocardiogenic syncope remain unclear. The simultaneous assessment of changes in endothelium-dependent and independent hormones and in autonomic balance in patients with tilt-induced syncope has been incompletely studied. Forty-six healthy subjects aged between 21 and 83 years (mean +/- SEM 47 +/- 3) underwent a 30-minute head-up tilt test at 60 degrees. Fourteen subjects (10 females and 4 male subjects) exhibited syncope at 16 +/- 2 minutes into the tilt. Hemodynamics were recorded every 5 minutes and blood samples for the measure of catecholamines, endothelin-1 (ET-1), and angiotensin-II (AT-II), were drawn at baseline, and 5, 10, 15, and 30 minutes into the tilt and immediately before syncope. Heart rate variability was analyzed by 5-minute segments during the test. Both catecholamines and ET-1 levels increased consistently in response to head-up tilt in subjects able to tolerate the test. Epinephrine increased to a greater extent before syncope. In contrast, ET-1 failed to increase at any time during the tilt and just before syncope. AT-II increased at 30 minutes into the tilt only in the control group. Finally, power in high-frequency bands decreased less in the group with syncope. Thus, compared with subjects able to tolerate a head-up tilt test, patients with syncope exhibit a greater increase in adrenomedullary activation, no significant increase in ET-1 levels, and a blunting in the decrease of vagal tone before syncope. The lack of increase in ET-1 during tilt may play a role in the inability to support orthostatic stress.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin II; Catecholamines; Endothelin-1; Female; Heart Rate; Humans; Male; Middle Aged; Signal Processing, Computer-Assisted; Syncope; Tilt-Table Test