Search

Abstract Background PITX2 is a bicoid-related homeodomain transcription factor that plays an important role in asymmetric cardiogenesis. Loss of function experiments in mice cause severe heart malformations, including transposition of the great arteries (TGA). TGA accounts for 5–7% of all congenital heart diseases affecting 0.2 per 1000 live births, thereby representing the most frequent cyanotic heart defect diagnosed in the neonatal period. Methods To address whether altered PITX2 function could also contribute to the formation of dTGA in humans, we screened 96 patients with dTGA by means of dHPLC and direct sequencing for mutations within the PITX2 gene. Results Several SNPs could be detected, but no stop or frame shift mutation. In particular, we found seven intronic and UTR variants, two silent mutations and two polymorphisms within the coding region. Conclusion As most sequence variants were also found in controls we conclude that mutations in PITX2 are not a common cause of dTGA.

Objectives: Wilson's disease is reported to have autonomic dysfunction, but comprehensive evaluation of autonomic function is lacking. Additionally, little is known about the change of autonomic function of Wilson's disease during continuous therapy. We assumed that patients with Wilson's disease had both sympathetic and parasympathetic autonomic impairments, and the autonomic dysfunction might be stable across a 3-year follow-up after years of optimal treatment. Methods: Twenty-six patients with Wilson's disease and twenty-six healthy controls were recruited. Twenty patients in the Wilson's disease group were examined again after a 3-year follow-up. All the participants were evaluated by a questionnaire on dysautonomia symptoms, 24-h blood pressure and heart rate monitoring, and cardiovascular autonomic function examination in various conditions including at rest, deep breathing, Valsalva maneuver, isometric handgrip test and passive tilting. Baroreflex sensitivity and spectral analyses were performed via trigonometric regressive spectral analysis. Results: Patients with Wilson's disease showed autonomic dysfunction mainly in the following aspects: (1) the heart rate was higher than the controls. (2) Valsalva ratio was lower in patients with Wilson's disease compared with the controls. (3) Heart rate increase during isometric hand gripping was smaller in the Wilson's disease patients than the controls. (4) Baroreflex sensitivity was lower during nearly all the cardiovascular autonomic function examinations compared with healthy controls. When tested 3 years later, baroreflex sensitivity at rest decreased compared with baseline. (5) There were mild declines of resting DBP and low frequency component of heart rate variability during the follow-up examination compared with baseline. (6) Subgroup analysis showed that patients initially presenting with neurological symptoms had a higher night-time heart rate, lower expiration: inspiration RR interval ratio (E/I ratio), lower expiration: inspiration RR interval difference (E-I difference), less increase of heart rate and diastolic blood pressure during the handgrip test, and lower baroreflex sensitivity during deep breathing than the control group. (7) Correlation analysis showed that the severity of neurological symptoms was associated with E/I ratio, E-I difference, Valsalva ratio, heart rate change during the handgrip test, and baroreflex sensitivity during deep breathing. Conclusions: The present study reveals cardiovascular autonomic dysfunction involving both sympathetic and parasympathetic branches in Wilson's disease patients, which is especially significant in the patients with neurological onset. Autonomic function is generally stable undergoing optimal maintenance treatment in patients with Wilson's disease. Though there might be mild changes of specific parameters. [ABSTRACT FROM AUTHOR]

Objective: It is well-known that initiation of fingolimod induces a transient decrease of heart rate. However, the underlying cardiac autonomic regulation is poorly understood. We aimed to investigate the changes of autonomic activity caused by the first dose of fingolimod using a long-term multiple trigonometric spectral analysis for the first time. In addition, we sought to use the continuous Holter ECG recording to find predictors for fingolimod induced bradycardia. Methods: Seventy-eight patients with relapsing-remitting multiple sclerosis (RRMS) were included. As a part of the START study (NCT01585298), continuous electrocardiogram was recorded before fingolimod initiation, and until no <6 h post medication. Time domain and frequency domain heart rate variability (HRV) parameters were computed hourly to assess cardiac autonomic regulation. A long-term multiple trigonometric regressive spectral (MTRS) analysis was applied on successive 1-h-length electrocardiogram recordings. Decision tree analysis was used to find predictors for bradycardia following fingolimod initiation. Results: Most of the HRV parameters representing parasympathetic activities began to increase since the second hour after fingolimod administration. These changes of autonomic regulations were in accordance with the decline of heart rate. Baseline heart rate was highly correlated with nadir heart rate, and was the only significant predicting factor for fingolimod induced bradycardia among various demographic, clinical and cardiovascular variables in the decision tree analysis. Conclusions: The first dose application of fingolimod enhances the cardiac parasympathetic activity during the first 6 h post medication, which might be the underlying autonomic mechanism of reduced heart rate. Baseline heart rate is a powerful predictor for bradycardia caused by fingolimod. [ABSTRACT FROM AUTHOR]

Underlying mechanisms of increased pressor responses to stress in Blacks are poorly understood. Cardiovascular regulation of normotensive Black ( n = 43) and Caucasian ( n = 90) Africans was studied during a cold pressor and color-word conflict test. Autonomic evaluation was performed by spectral analysis. Higher diastolic pressor and heart rate responses to the cold pressor test were observed in Black compared to Caucasian Africans. Autonomic efferent outflow to stress was comparable between groups. Transient downregulation of baroreflex during stress was evident in Blacks but not in Caucasians. Greater diastolic pressor responses were related to a higher cardiac reactivity, a baroreflex desensitization, and higher stress perception in Black Africans. Thus, increased stress perception may facilitate cardiac and diastolic hyperreactivity, indirectly affecting baroreflex function in Black Africans. [ABSTRACT FROM AUTHOR]