Susan J. Corcoran

Summary: Objective: The objective of this study was to examine the cross‐sectional relationship between the expression of norepinephrine transporter (NET), the protein responsible for neuronal uptake‐1, and indices of glycaemia and hyperinsulinaemia, in overweight and obese individuals.Methods: Thirteen non‐medicated, non‐smoking subjects, aged 58 ± 1 years (mean ± standard error of the mean), body mass index (BMI) 31.4 ± 1.0 kg m⁻², with wide‐ranging plasma glucose and haemoglobin A1c (HbA1c, range 5.1% to 6.5%) participated. They underwent forearm vein biopsy to access sympathetic nerves for the quantification of NET by Western blot, oral glucose tolerance test (OGTT), euglycaemic hyperinsulinaemic clamp, echocardiography and assessments of whole‐body norepinephrine kinetics and muscle sympathetic nerve activity.Results: Norepinephrine transporter expression was inversely associated with fasting plasma glucose (r = −0.62,P = 0.02), glucose area under the curve during OGTT (AUC_0–120,r = −0.65,P = 0.02) and HbA1c (r = −0.67,P = 0.01), and positively associated with steady‐state glucose utilization during euglycaemic clamp (r = 0.58,P = 0.04). Moreover, NET expression was inversely related to left ventricular posterior wall dimensions (r = −0.64,P = 0.02) and heart rate (r = −0.55,P = 0.05). Indices of hyperinsulinaemia were not associated with NET expression. In stepwise linear regression analysis adjusted for age, body mass index and blood pressure, HbA1c was an independent inverse predictor of NET expression, explaining 45% of its variance.Conclusions: Hyperglycaemia is associated with reduced peripheral NET expression. Further studies are required to identify the direction of causality.

Objective: To establish the occurrence of an autosomal dominant form of vasovagal syncope (VVS) by detailed phenotyping of multiplex families and identification of the causative locus. Methods: Patients with VVS and a family history of syncope were recruited. A standardized questionnaire was administered to all available family members and medical records were reviewed. Of 44 families recruited, 6 were suggestive of autosomal dominant inheritance. Genome-wide linkage was performed in family A using single nucleotide polymorphism genotyping microarrays. Targeted analysis of chromosome 15q26 with microsatellite markers was implemented in 4 families; 1 family was too small for analysis. Results: Family A contained 30 affected individuals over 3 generations with a median onset of 8 to 9 years. The other families comprised 4 to 14 affected individuals. Affected individuals reported typical triggers of VVS (sight of blood, injury, medical procedures, prolonged standing, pain, frightening thoughts). The triggers varied considerably within the families. Significant linkage to chromosome 15q26 (logarithm of odds score 3.28) was found in family A. Linkage to this region was excluded in 2 medium-sized families but not in 2 smaller families. Sequence analysis of the candidate genes SLCO3A1, ST8SIA2, and NR2F2 within the linkage interval did not reveal any mutations. Conclusions: Familial VVS, inherited in an autosomal dominant manner, may not be rare and has similar features to sporadic VVS. The chromosome 15q26 locus in family A increases the susceptibility to VVS but does not predispose to a particular vasovagal trigger. Linkage analysis in the remaining families established likely genetic heterogeneity.

Vasovagal syncope (VVS) is the commonest cause of recurrent syncope and has a high level of morbidity in both young and elderly patients. Diagnosis and treatment are often unsatisfactory despite the fact that syncope has a lifetime cumulative incidence of 35%. A detailed history can often yield an accurate diagnosis in most young patients. Older patients are more likely to present in an atypical manner and although the yield is low, a more comprehensive diagnostic assessment may be needed. It is important to identify patients with low supine systolic blood pressure who are prone to recurrent VVS. These patients represent a distinct subtype of VVS and may respond to a tailored therapeutic approach. Treatment options for VVS are limited because of a paucity of randomized trials. The backbone of therapy is educating the patient, avoiding precipitating factors, maintaining hydration and the application of physical counter-pressure manoeuvres. Drug therapy is rarely warranted; however, fludrocortisone, alpha-agonists, such as midodrine and dihydroergotamine, and selective serotonin reuptake inhibitors may be helpful in some patients. Permanent cardiac pacing is rarely needed and randomized trials do not support its use.

Postural syncope is a transient loss of consciousness secondary to a reduction in cerebral blood flow and is typically precipitated by standing. It is the commonest cause of recurrent transient loss...

Programmed upper rate pacing occurred in a patient with a rate‐adaptive pacemaker when he was connected to a cardiac monitor in an emergency department. The tachycardia was mistakenly interpreted to be ventricular tachycardia and the patient received multiple DC shocks as well as intravenous amiodarone and sotalol, resulting in severe hemodynamic deterioration. It is important that physicians working in the hospital environment be familiar with this pacemaker‐monitor interaction as the problem may be easily rectified by disconnecting the monitor or by reprogramming the pacemaker to a nonrate‐adaptive pacing mode.