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Background: Congestive heart failure is characterised by enhanced immune activation. Immune-mediated mechanisms may play a pathogenic role, hence the growing interest in therapeutic regimens that could modulate the immune response in heart failure., Material and Methods: In the present report we discuss the pathogenic role of immunological and inflammatory mediators in the pathophysiology of heart failure and discuss different treatment modalities with focus on our recent study with intravenous immunoglobulin. In that study 40 patients with symptomatic chronic heart failure and left ventricular ejection fraction (LVEF) < 40% were randomised in a double-blind fashion to receive therapy with immunoglobulin or placebo for a total period of 26 weeks., Results: We found that intravenous immunoglobulin, but not placebo, shifted the cytokine balance in an anti-inflammatory direction, and that such a shift was associated with improvement in LVEF by 5 EF units. Functional capacity and haemodynamic variables also improved., Interpretation: Our study supports the hypothesis that immunological variables might be of significant importance in the pathogenesis of heart failure and it suggests a potential for immunomodulating therapy in addition to optimal conventional cardiovascular treatment regimens in such patients. These issues are further discussed in the present article.

Background: Fabry's disease is an X-linked inborn error of metabolism. The patients lack or have very low activity of the enzyme alpha-galactosidase A. This results in deposition of sphingolipids in endothelial cells and vascular smooth muscle cells; thus the disease can affect nearly every organ in the body. Renal failure is the most common cause of death, but cardiac involvement is frequent., Material and Methods: We describe two brothers with Fabry's disease and provide a review of the literature in the field., Results: Both patients had extensive electro- and echocardiographic findings., Interpretation: Fabry's disease should be suspected in men with unexplained electro- and/or echocardiographic signs of left ventricular hypertrophy and a short PQ interval in the ECG.

Concomitant use of digitoxin and enzyme-inducing antiepileptics may lower serum levels, and accordingly the effect of digitoxin, unless the higher metabolic clearance is compensated for by higher dosage. Use of digitoxin is almost always guided by serum concentration measurements. Information on a possible enzyme-inducing effect of phenobarbital, phenytoin and carbamazepine is easily accessible. Compilation of serum level measurements for digitoxin showed that serum levels shifted towards lower values during concomitant use of phenytoin or carbamazepine than when digitoxin was used alone. As a consequence, the fraction of patients with serum levels below the therapeutic range was doubled. Concomitant use of phenobarbital did not cause a shift in the levels of digitoxin. In fact, in this group, a larger fraction of the serum level measurements were within the therapeutic range. Thus, the dosage of digitoxin appears to be fully compensated during concomitant use of phenobarbital, but obviously deserves attention during concomitant use of phenytoin or carbamazepine.

Reduced heart rate variability (HRV) is an independent risk factor after myocardial infarction, indicating higher risk of fatal and nonfatal arrhythmias and of cardiac death in general. Analysis of HRV is also a valuable tool in clinical research, providing a non-invasive measurement of fluctuations in sympathetic and parasympathetic activation. We expect increased use of these methods, since new 24-hour: ECG-monitoring equipment is to be delivered with software for HRV as an option. Statistical time domain analysis of the whole 24-hour system of recording is very suitable for stratifying risk after myocardial infarction. Frequency domain analysis requires manual as well as automatic editing, but is the method of choice in clinical research involving short-term recordings and standardized conditions.

Radiofrequency ablation of the bundle of His was performed in 33 patients with intractable atrial arrhythmias (fibrillation in 23, flutter in seven, atrial tachycardia in three). Complete AV block was produced in 30 patients, and clinically satisfactory incomplete block in another two. All were subsequently treated by pacemaker. The ablation was a failure in one patient with hypertrophic cardiomyopathy. Today ablation can be targeted at atrial tachycardias and flutter, and ablative modification of the AV node can reduce ventricular rate in chronic atrial fibrillation. However, His bundle ablation is still the treatment of choice in drug refractory atrial fibrillation when no other measure can provide adequate rate control.

The authors review the first 150 patients with cardiac arrhythmias who were treated with radio-frequency ablation at a Norwegian arrhythmia centre. The clinical success rate (either electrophysiological cure or a dramatic reduction in the severity and frequency of the attacks) was 97%. 11 patients were treated for two or more arrhythmias. In 27 patients two, occasionally three, sessions were required to obtain a satisfactory clinical result. Repeat ablation is scheduled for three cases where the treatment was unsuccessful. Among 190 ablations, 13 complications occurred, none of which resulted in permanent sequelae. The time spent on each procedure, and particularly the long time spent on fluoroscopy during the earlier procedures, demonstrates the existence of a learning curve for ablation. This lends support to the authorities' restriction of treatment of arrhythmias by ablation to only two laboratories in a population of four million.

Therapeutic drug monitoring includes measurement of serum concentrations of drugs when this is possible and appropriate. A therapeutic range is defined for populations where the serum levels represent an optimal relationship between clinical effects and side effects for most of the individuals in the population. Compared with the rest of the population, some individuals are atypical, both with respect to response to and elimination of drugs. Therapeutic drug monitoring makes individualization of dosages in these individuals easier, but often requires extra effort. Compilation of serum level measurements for different drugs for a period of six months showed that the tailoring of digitoxin, carbamazepine, lithium and phenobarbital is as close to optimal as can be expected for a population. For amitriptyline, digoxin and theophylline, a considerable increase in clinical effect within a population of users could probably be achieved by bringing more individual serum levels from the subtherapeutic into the therapeutic range. Nor does the therapeutic potential of phenytoin, nortriptyline and valproate seem to be fully utilized.