Electrophysiologic mechanisms for ventricular arrhythmias in left ventricular dysfunction: electrolytes, catecholamines and drugs.

Cardiac arrhythmias are generated as the result of disorders of automaticity or of impulse conduction. Regardless of the mechanism, calcium is likely to be involved, although calcium antagonists are rarely useful antiarrhythmics in ventricular arrhythmias. Myocardial cells that do not ordinarily initiate action potentials may do so when they are partially depolarized, giving rise to an ectopic focus. Early afterdepolarizations (EADs) are also induced in cardiac cells by partial depolarization, whereas delayed afterdepolarizations (DADs) are induced by Ca++ overloading. EADs may be the initiating mechanism of torsade de pointes, a complication of QT prolongation associated with quinidine therapy. Both in the animal model and in humans, treatment with magnesium, isoproterenol, or pacing, all of which suppress EADs, will also suppress torsade de pointes. Ventricular tachycardia is a manifestation of ordered re-entry, and may be exacerbated by antiarrhythmics, especially class 1c drugs. In the individual patient, prediction of proarrhythmia is not possible. The risk of proarrhythmia is increased in patients with episodes of sustained ventricular tachycardia or with significant left ventricular dysfunction.

Initial and steady state pharmacokinetics of cilazapril in congestive cardiac failure.

Twenty one patients with NYHA class II-III congestive heart failure received single ascending doses of 0.5, 1.25 and 2.5 mg cilazapril daily followed by the minimum effective dose for six weeks. Fifteen patients completed the study, but the data from only 11 were sufficiently complete for kinetic evaluation. The pharmacokinetics of the metabolite, cilazaprilat, after a single dose of 0.5 mg cilazapril were similar to previous observations in healthy volunteers at identical dosage. Repeat administration, however, led to greater accumulation than previously observed in volunteers at the higher dosages of 1.25 or 5 mg given for 8 days. Seven patients experienced adverse events. Four were severe, leading to withdrawal of the patients from the study, but only one event was related to cilazapril. Of the other three, one suffered a myocardial infarction and subsequently died due to worsening congestive heart failure. One other patient was withdrawn with two adverse events probably related to cilazapril. No other deaths occurred amongst the study population, and there were no significant abnormalities in haematology or blood chemistry.

A study of the use of flecainide acetate in the long-term management of cardiac arrhythmias.

One hundred and sixty-nine patients with a wide range of cardiac arrhythmias and who had been treated with chronic oral flecainide acetate were reviewed retrospectively. The most common arrhythmia was atrial fibrillation (32%), and 20% of the patient population had the Wolff-Parkinson-White syndrome. Five hundred and three treatment episodes were assessed, 254 with flecainide alone or in combination, mean duration 7.3 +/- 9.4 months, and 249 without flecainide, mean duration 9.5 +/- 12.3 months. The most common dose for flecainide was 200 mg/day (57% of episodes), and it was used alone in 82% of flecainide treatment episodes. Arrhythmia frequency was reduced or abolished in 73% of flecainide treatment episodes, with little difference between arrhythmia groups. Unwanted effects were seen in 14% of flecainide treatment episodes, and half of these cases were managed by dose adjustment. It is concluded that flecainide acetate is effective in a wide range of cardiac arrhythmias, and that long-term management problems are few.

Influence of respiratory variations on right ventricular function.

Respiratory effort during inspiration, expiration, and the Valsalva manoeuvre changes right ventricular preload and afterload. On inspiration these changes should improve systolic emptying of a larger end diastolic volume and so increase the ejection fraction, whereas on expiration the reverse should be true. The resting right ventricular ejection fraction was measured by first pass radionuclide angiography with gold-195m (half life 30.5 s) in 17 individuals at maximal inspiration and expiration and in eight at rest and during the strain phase (phase 2) of the Valsalva manoeuvre. The right ventricular ejection fraction was significantly lower during expiration than during inspiration. There were, however, no significant differences in bolus duration or right ventricular transit time. The Valsalva manoeuvre, in contrast, significantly increased the ejection fraction and also significantly prolonged both the bolus duration and right ventricular transit time. The conformation of the bolus curves during the Valsalva manoeuvre suggested the development of tricuspid regurgitation. These data suggest that relative influences of venous return, pulmonary arterial pressure, pulmonary vascular resistance, and possible functional tricuspid regurgitation vary during inspiration, expiration, and the Valsalva manoeuvre and can affect the right ventricular ejection fraction. Changes in right ventricular function on exercise assessed by first pass radionuclide angiography must be interpreted with caution because maximal respiratory effort may alter the right ventricular ejection fraction independently of ischaemia or other non-ischaemic factors.

Unusual echocardiographic appearance of intracardiac thrombi in a patient with endomyocardial fibrosis.

A five year old girl presented with a four month history of recurrent heart failure, which subsequently proved to be caused by endomyocardial fibrosis. There was no evidence of valvar disease. Echocardiography showed several echogenic masses with echolucent centres within the cardiac cavity. Histological examination showed that these masses were partly organised thrombus.