Prognosis of fetuses with hydrops and tachyarrhythmia has been portrayed as poor in most published reports. This might lead to biased counselling, unnecessary caesarean section, preterm delivery, and even termination of pregnancy.

To evaluate contemporary fetal and postnatal outcomes of hydropic fetuses with fetal tachyarrhythmia when it is treated effectively and monitored systematically.

This is a retrospective review of a single centre experience at the University Hospital of Wales over a 20-year period. All fetuses received high doses of flecainide and digoxin combination treatment. Tachycardia response rate, time to arrhythmia and hydrops resolution, fetal and postnatal morbidity, and mortality rates were analysed.

Twenty fetuses were diagnosed with hydrops fetalis and received treatment. The mechanism of fetal tachyarrhythmia was supraventricular tachycardia in thirteen and atrial flutter in eight cases. Among the 20 fetuses treated, the overall tachycardia response rate was 90% (18/20) with the restoration of sinus rhythm in 85% (17/20) of the cases. The median time to restore sinus rhythm or to rate control of the arrhythmia was 1.5 days (range 12 hours to 13 days). Hydrops resolved in 17 of the 20 fetuses, with a median time of 12 days (range 3–21 days). Four fetuses went into spontaneous preterm birth and one fetus was delivered early due to worsening hydrops. No significant neurological morbidity was observed in surviving neonates and infants on clinical examination. There was one postnatal death due to respiratory complications of prematurity in the non-responsive supraventricular tachycardia case.

High-dose flecainide and digoxin combination offers effective treatment strategy in fetuses with hydrops and tachyarrhythmia with favourable outcomes. This study may guide more realistic counselling for pregnancies complicated by tachyarrhythmia and hydrops.

Newborn atrial flutter can be treated by medications, pacing, or direct current cardioversion. The purpose is to compare the cost-effectiveness of digoxin, pacing, and direct current cardioversion for the treatment of atrial flutter in neonates.

A decision tree model was developed comparing the efficacy and cost of digoxin, pacing, and direct current cardioversion based on a meta-analysis of published studies of success rates of cardioversion of neonatal atrial flutter (age<2 months). Patients who failed initial attempt at cardioversion progressed to the next methodology until successful. Data were analysed to assess the cost-effectiveness of these methods with cost estimates obtained from 2015 Medicare reimbursement rates.

The cost analysis for cardioversion of atrial flutter found the most efficient method to be direct current cardioversion at a cost of $10 304, pacing was next at $11 086, and the least cost-effective was digoxin at $14 374. The majority of additional cost, regardless of method, was from additional neonatal ICU day either owing to digoxin loading or failure to covert. Direct current cardioversion remains the most cost-effective strategy by sensitivity analyses performed on pacing conversion rate and the cost of the neonatal ICU/day. Direct current cardioversion remains cost-effective until the assumed conversion rate is below 64.6%.

The most cost-efficient method of cardioverting a neonate with atrial flutter is direct current cardioversion. It has the highest success rates based on the meta-analysis, shorter length of stay in the neonatal ICU owing to its success, and results in cost-savings ranging from $800 to $4000 when compared with alternative approaches.

Serum digoxin levels have limited utility for determining digoxin toxicity in adults. Paediatric data assessing the utility of monitoring serum digoxin concentration are scarce. We sought to determine whether serum digoxin concentrations are associated with signs and symptoms of digoxin toxicity in children.

We carried out a retrospective review of patients <19 years of age who received digoxin and had serum digoxin concentrations assessed between January, 2007 and June, 2013. Data collection included patient demographics, digoxin indication, serum digoxin concentrations, signs and symptoms of digoxin toxicity, electrocardiograms, and co-morbidities. Reviewers performing chart review and electrocardiogram analysis were blinded to digoxin levels. Descriptive statistical methods were used and comparisons were made between patients with and without toxic serum digoxin concentrations (>2 ng/ml).

There were 87 patients who met study criteria (male 46%, mean age 8.4 years). CHD was present in 67.8% and electrocardiograms were performed in 72.4% of the patients. The most common indication for digoxin toxicity was heart failure symptoms (61.5%). Toxic serum digoxin concentrations were present in 6.9% of patients (mean 2.6 ng/ml). Symptoms associated with digoxin toxicity occurred in 48.4%, with nausea/vomiting as the most common symptom (36.4%), followed by tachycardia (29.5%). Compared with those without toxic serum digoxin concentrations, significantly more patients with toxic serum digoxin concentrations were female (p=0.02). The presence of electrocardiogram abnormalities and/or signs and symptoms of digoxin toxicity was not significantly different between patients with and without serum digoxin concentrations (p>0.05).

Serum digoxin concentrations in children are not strongly associated with signs and symptoms of digoxin toxicity.

The study assessed the biochemical differences between right hemispheric-dominant and left hemispheric-dominant individuals. The chemical hemispheric-dominance in various systemic and neuropsychiatric diseases was also studied.

The isoprenoid metabolites, digoxin, dolichol and ubiquinone, glycoconjugate metabolism, free radical metabolism and the RBC membrane composition, were studied in individuals with differing hemispheric-dominance. The digoxin levels and RBC membrane Na+-K+ATPase activity were also studied in systemic and neuropsychiatric diseases.

The results showed that right hemispheric-dominant individuals had elevated digoxin levels, increased free radical production and reduced scavenging, increased tryptophan catabolites and reduced tyrosine catabolites, increased glycoconjugate levels and increased cholesterol : phospholipid ratio of RBC membranes. Left hemispheric-dominant individuals had the opposite patterns. This patterns could be correlated with various systemic and neuropsychiatric diseases.

Right hemispheric-dominance represents a hyperdigoxinaemic state with membrane sodium–potassium ATPase inhibition. Left hemispheric-dominance represents the reverse pattern with hypodigoxinaemia and membrane sodium–potassium ATPase stimulation. Hemispheric-dominance could predispose to various systemic and neuropsychiatric diseases.

The isoprenoid pathway produces three key metabolites: endogenous digoxin (membrane sodium-potassium ATPase inhibitor, immunomodulator and regulator of neurotransmitter/amino acid transport), dolichol (regulates N-glycosylation of proteins) and ubiquinone (free radical scavenger). The role of the isoprenoid pathway in the pathogenesis of sarcoidosis in relation to hemispheric dominance was studied.

The isoprenoid pathway-related cascade was assessed in patients with systemic sarcoidosis with pulmonary involvement. The pathway was also assessed in patients with right hemispheric, left hemispheric and bihemispheric dominance for comparison to find out the role of hemispheric dominance in the pathogenesis of sarcoidosis.

In patients with sarcoidosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in the cholesterol:phospholipid ratio and a reduction in the glycoconjugate level of red blood cell (RBC) membrane in this group of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. In individuals with left hemispheric dominance the patterns were reversed.

Endogenous digoxin, by activating the calcineurin signal transduction pathway of T cells, can contribute to immune activation in sarcoidosis. An altered glycoconjugate metabolism can lead to the generation of endogenous self-glycoprotein antigens in the lung as well as other tissues. Increased free radical generation can also lead to immune activation. The role of a dysfunctional isoprenoid pathway and endogenous digoxin in the pathogenesis of sarcoidosis in relation to right hemispheric chemical dominance is discussed. All the patients with sarcoidosis were right-handed/left hemispheric dominant according to the dichotic listening test, but their biochemical patterns were suggestive of right hemispheric chemical dominance. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test.

This study assessed the changes in the isoprenoid pathway and its metabolites in seizure disorder (ILAE classification – I generalized – idiopathic generalized epilepsy with age-related onset – epilepsy with generalized tonic clonic seizures on awakening) and the metabolic cascade produced by isoprenoid pathway dysregulation.

The following parameters were assessed in seizure disorder: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugates metabolism and red blood cell (RBC) membrane composition.

There was elevation in plasma HMG-CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na-K+ ATPase activity, serum magnesium and ubiquinone levels. Serum tryptophan, serotonin, strychnine, nicotine and quinolinic acid were elevated while tyrosine, dopamine, morphine and norepinephrine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions (except dermatan sulfate), the activity of glycosaminoglycans (GAG) degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. Total serum cholesterol, LDL cholesterol and free fatty acids were increased while HDL cholesterol and triglycerides were unaltered. The concentration of membrane hexose, fucose, cholesterol and phospholipids in the RBC membrane decreased significantly but the total RBC membrane GAG was unaltered.

Epileptogenesis could be due to a dysfunctional isoprenoidal pathway and paroxysmal hypothalamic digoxin hypersecretion.

The isoprenoid pathway was assessed in 15 patients with chronic fatigue syndrome (CFS). The pathway was also assessed in individuals with differing hemispheric dominance to assess whether hemispheric dominance has any correlation with these disease states.

The isoprenoid metabolites – digoxin, dolichol and ubiquinone – RBC membrane Na+-K+ ATPase activity, serum magnesium and tyrosine/tryptophan catabolic patterns were assessed. The free radical metabolism, glycoconjugate metabolism and RBC membrane composition were also assessed.

Membrane Na+-K+ ATPase activity and serum magnesium levels were decreased while HMG-CoA reductase activity and serum digoxin levels were increased in CFS. There were increased levels of tryptophan catabolites – nicotine, strychnine, quinolinic acid and serotonin – and decreased levels of tyrosine catabolites –dopamine, norepinephrine and morphine – in CFS. There was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual glycosaminoglycans (GAG) fractions and lysosomal enzymes in CFS. Reduced levels of ubiquinone, reduced glutathione and free radical scavenging enzymes as well as increased lipid peroxidation products and nitric oxide were noticed in CFS. The biochemical patterns in CFS correlated with those obtained in right hemispheric dominance.

The role of hypothalamic digoxin and neurotransmitter-induced immune activation, altered glycoconjugate metabolism and resultant defective viral antigen presentation, NMDA excitotoxicity and cognitive and mitochondrial dysfunction in the pathogenesis of CFS is stressed. CFS occurs in individuals with right hemispheric dominance.

To evaluate the efficacy of flecainide and digoxin combination in foetal supraventricular tachycardia.

This study was carried out in a tertiary referral centre.

We conducted a retrospective review of 29 patients diagnosed with supraventricular foetal tachycardia between 2001 and 2009. Mode of presentation, foetal cardiac function, maternal anti-arrhythmic serum levels, drug tolerance, and maternal electrocardiogram recordings were assessed. The postnatal outcome of each infant was also evaluated for tachycardia recurrence.

In all, 27 foetuses were treated with digoxin and flecainide combination, and two foetuses were delivered without any treatment. Of the 27 foetuses, seven had atrial flutter and the remaining 22 had atrioventricular re-entry tachycardia. There were eight foetuses with hydrops (27%), of whom three had atrial flutter and five had atrioventricular re-entry tachycardia; 26 foetuses (96%) responded to flecainide and digoxin combination, with restoration of sinus rhythm in 22 (81.4%) and rate control in the other four. In one severely hydropic foetus, there was no response to treatment. In all, 26 treated infants were delivered alive, but one pregnancy was terminated for non-cardiac causes when the foetus was in sinus rhythm. There was no intrauterine death due to tachycardia. Although there were minor side effects to anti-arrhythmic medications, none of the pregnant women developed proarrhythmia.

Flecainide and digoxin combination treatment offers a safe and effective treatment for foetal supraventricular tachycardia with fast restoration of sinus rhythm.