University of München, Germany
* Correspondence to: Prof. Gerhard Steinbeck, Med. Hosp. I, Klinikum Grosshadern, University of München, Marchioninistrasse 15, 81377 Munich, Bavaria, Germany. Tel.: +49-89-7095-2370; fax: +49-89-7095-8870 (E-mail: gerhard.steinbeck{at}med1.med.uni-muenchen.de).
This editorial refers to "Heart rate is a predictor of success in the treatment of adults with symptomatic paroxysmal supraventricular tachycardia" by P. Ballo et al. on page 1310
Paroxysmal supraventricular tachycardia (PSVT) with sudden onset and termination is relatively common, the estimated prevalence in the normal population being 2.25 per 1000.1 It is a frequent cause of visits to the emergency room or primary care physician. In young adults, there is usually no structural heart disease and females have a twofold greater risk of developing this arrhythmia than males.1 Electrocardiographically, supraventricular tachycardia is defined as a regular tachycardia with QRS-complexes of supraventricular origin (usually narrow, these complexes are broad in the presence of aberrant conduction, conduction defects or accessory pathway conduction) and with P-waves which are either absent or have abnormal, non-sinus morphology.2 The electrophysiological mechanism is not uniform. Most commonly it is atrioventricular nodal reciprocating tachycardia, followed by the less common atrioventricular reciprocating tachycardia using an accessory pathway, and atrial tachycardia. If the patient is in a haemodynamically stable situation, a brief clinical examination is performed, a history is taken and a 12 lead ECG is recorded, carotid sinus massage should be initiated to terminate the arrhythmia according to our guidelines.2 If this fails, antiarrhythmic drugs should be administered intravenously. While adenosine or non-dihydropyridine calcium-channel antagonists (verapamil, diltiazem) are the drugs of choice, adenosine is becoming the preferred agent relative to calcium-channel- or beta-blockers (with the exception of patients with severe asthma) because of its rapid onset of action and very short half-life.2
In this issue of the Journal, Ballo et al.3 report their analysis on the relationship between the rate of the tachycardia and the potential of adenosine, verapamil, and carotid sinus massage to terminate the arrhythmia in a series of 106 adults. Adenosine and verapamil were similarly effective in terminating PSVT (74.4% and 81.8%, respectively), whereas the efficacy of carotid sinus massage was significantly lower (32.4%). Interestingly, the efficacy of the two drugs was dependent upon the rate of the tachycardia in an opposite manner: following adenosine, the probability of tachycardia termination was >75% for rates of tachycardia over 166 beats/min, and rapidly decreased at lower tachycardia rates down to 25% at a rate of 138 beats/min. Conversely, following verapamil the probability of tachycardia termination was >75% for heart rates lower than 186 beats/min, but decreased at faster rates (25% probability of success at 241 beats/min). This effect of heart rate on the efficacy of verapamil was somewhat smaller than the opposite effect of heart rate on the efficacy of adenosine. No significant effects of tachycardia rates on the success of termination were observed in the patient group undergoing carotid sinus massage. A comparison of the two probability curves obtained in the adenosine and verapamil group suggests that a tachycardia with a rate ⩾173 beats/min or more is more effectively treated with adenosine, whereas lower rates of tachycardia may be associated with a better efficacy of verapamil.
Are these data convincing?
First, as outlined by the authors, the exact electrophysiological mechanism of PSVT in the 106 patients was not defined by an invasive electrophysiological study. Possible mechanisms include increased automaticity, triggered activity, and both micro- and macro-re-entry in the atrium and AV node tissue. These mechanisms are known to be of major importance for drug efficacy, as an example, of adenosine has a lesser efficacy in focal atrial tachycardia.
Second, it should be stressed that the interesting observation by Ballo et al., was based on a retrospective analysis in which 39 patients received adenosine, 33 patients verapamil, and 34 patients carotid sinus massage. Before firm conclusions can be drawn, we need a prospective, randomised trial comparing adenosine with verapamil in larger groups of patients with a well-defined tachycardia mechanism.
What might be the cause of the opposite rate-dependent efficacy of adenosine and verapamil in PSVT?
As outlined by the authors, the pharmacodynamic effects of both adenosine and verapamil have been reported to be rate-dependent. The main mechanism of adenosine is antagonism of the beta-adrenergic system by inhibition of catecholamine-stimulated adenylate cyclase activity. In addition, activation of a potassium current may also play a role.4
Verapamil inhibits the slow inward current due to its blocking effect on the L-type calcium channels; an additional mechanism might be inhibition of the rapid component of the delayed rectifier potassium current. Thus, it was recently shown that verapamil led to a prolongation of the atrial effective refractory period in healthy adults at low heart rates, and to a shortening at high rates, which suggests a predominant effect on calcium current at fast rates and a predominant effect on the delayed rectifier potassium current at slow rates.5
Given the reasonable assumption that activation of the adrenergic system plays a decisive role in very rapid supraventricular tachycardia, effective blockade of the adrenergic input by adenosine and not by verapamil could explain the higher efficacy of adenosine when the tachycardia rate is very high. Trying to explain differences in the rate-dependence of action between adenosine and verapamil in terms of interaction with various ion channels remains pure speculation at present.
In summary
The choice between adenosine and verapamil for the treatment of PSVT is currently governed by personal experience and preferences, the desired onset and duration of drug action, known hypersensitivities, intolerance or contraindications for the two drugs, and cost. Ballo et al. tell us that the rate of tachycardia is a simple criterion to guide our decision to use these drugs effectively. However, before we definitely accept this new, interesting and clinically relevant information, confirmation in a prospective, randomised trial using larger and better defined patient groups with PSVT is needed.
Footnotes
doi:10.1016/j.ehj.2004.05.011.
References
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