CURRICULUM

IN CARDIOLOGY

Acute management of paroxysmal atrioventricular junctional reentrant supraventricular tachycardia: Pharmacologic strategies Sami Viskin,

MD, and Bernard

Belhassen, MD. TeZ Auk,

Paroxysmal supraventricular tachycardia mediated by a reentry mechanism involving the atrioventricular (AV) node, that is, paroxysmal AV junctional reentrant tachycardia (PJRT), is one of the most frequently encountered cardiac arrhythmias in clinical practice. Episodes of PJRT are frequently of short duration, terminating spontaneously or by vagal maneuvers performed by the patient himself or a physician.l However, episodes of sustained PJRT refractory to vagal maneuvers may represent a medical emergency. During the last two decades, verapamil has replaced digoxin and edrophonium chloride as the drug of choice for the acute management of PJRT refractory to vagal maneuvers2-” in view of its high rate of efficacy and more rapid action.” Nevertheless, rare yet serious adverse effects of intravenous verapamil administration have been reported.7-g Many others drugs, such as adenosine,l”-‘y adenosine triphosphate (ATP),l”$ 2o-27 ajmaline,28-“o diltiazem,31-33 flecainide,34-4” and propafenone,41-44 have also been shown to be highly effective in the acute management of PJRT. In the present article we review the pharmacologic options for termination of PJRT, giving special attention to the newer antiarrhythmic drugs. Guidelines for the acute management of PJRT in various clinial settings are proposed. ELECTROPHYSIOLOGIC

CONSIDERATIONS

Unidirectional block, delayed conduction, and distal recovery of excitability within anatomically From the Department of Cardiology, Tel Aviv Medical Center, pital, and Sackler School of Medicine, Tel Aviv liniversity. Received

for publication

Jan.

It?. 1990;

Reprint requests: Bernard Relhassen, Aviv Medical Center, lchilw Hospital, rael. 4/1/20485

180

accepted

Feb.

Ichilcw

Hos-

26. 1990.

MD. Department of Cardiology. Trl W&man R St.. Tel Avil- 64 39. Is-

Israel

contiguous but functionally diverse myocardial tissue are the pathophysiologic requisites for a selfperpetuated reentrant arrhythmia. The two major types of reentrant arrhythmias involving the AV node are AV nodal reentry tachycardia (AVNRT) and AV reentry (also called reciprocating) tachycardia (AVRT). In AVNRT the whole reentry circuit is located within the AV node and is formed by a slow pathway with a short refractory period commonly conducting antegradely and a fast pathway with a long refractory period commonly conducting retrogradely. In AVRT an extranodal accessory pathway provides the closing loop, usually the retrograde limb of the circus movement, the antegrade limb of which is the AV node. In any case, a critical relationship between conduction velocity and refractory periods within the circuit must be maintained for its initiation and propagation. Thus either conduction delay or increase in refractoriness of any limb of the reentry circuit will result in termination of PJRT.45 The main electrophysiologic effects of pertinent antiarrhythmic drugs are listed in Table I. Calcium channel blockers and adenosine compounds mainly affect the slow antegrade AV nodal pathway (or the AV node in patients with AVRT). In contrast, class I antiarrhythmic drugs such as ajmaline, propafenone, or flecainide exert their main action on the retrograde (fast AV nodal or accessory pathway) limb of the reentrant circuit. DRUG

HALF-LIFE

The half-life of different intravenous antiarrhythmic drugs with proved effectiveness in the acute management of PJRT is shown in Table II. The shorter the half-life of a given drug, the smaller the chance for serious drug-related adverse effects. A major advantage of drugs with an ultrashort half-life, such as adenosine compounds, is that they can be

Volume

120

Number

1

Table

I. Electrophysiologic

Acute management of PSVT and ECG effects of antiarrhythmic

Verapamil*

SRCL PR

QRS QTc SNRT AH HV Atria1 AV node Slow Fast H-P V AP

C R R c R C R R R C R

0 + 0 0 0 + 0 0 0 +

Ajmaline

I 8I

drugs ATP Adenosine

Flecainide

t t 0 0

+ + o+ 0 -o+ + -

O+ tt 0 o+ ot +

NA +t 0 NA NA NA

+ +o-

+ ++ ++ + t+

-

t o+

Propafenone o+ t ot ot ot t

t t

-

-

NA 0 NA NA NA 0 NA

+

++

+-It+ +t tt

ATP, Adenosine triphosphate; SRCL, sinus rhythm cycle length; SNRT, sinus node recovery time; C, conduction velocity; R, refractoriness; Slow and Fast, slow and fast AV nodal pathways, respectively; V, ventricular; AP, accessory pathway: +, increase; -, decrease; 0, no change; NA, not available. *Essentially similar data for diltiazem.

administered repeatedly in increasing dosages without toxic effects; another advantage is that in case of failure subsequent administration of a second antiarrhythmic drug is possible without fear of adverse drug interactions. On the other hand, drugs with a long half-life, such as calcium channel blockers, flecainide, and propafenone, have the potential advantage of preventing an immediate recurrence of the arrhythmia. In addition, reinducibility of PJRT during electrophysiologic study can be assessed for longacting drugs only, and in the case of flecainide46 can be used for predicting arrhythmia prevention during long-term oral therapy.

II. Mean plasma elimination half-life after intravenous administration of antiarrhythmic drugs

Table

Drug

Adenosine compounds Ajmaline Propafenone Verapamil Flecainide

Half-life

) 58/59 (98’; ) 41/42 (98Cr ) 57158 (98Y ) 98/100 (98”; ) 18/18 (lOOr;) 8/12 (66.7%) 26/30 (86.7 % ) 9/9 (loo”< ) 39/48 (81”; ) 48157 (84’; ) 75/84 (89.3 Cc.) 42155 (76.4’;.) 117/139 (84.Zp; f

of arrhythmia Time (mean) 40-120 (80)

Mode set

r 253 mm

ANT-SP ANT-AVN ANT-SP ANT-AVN

520

set

ANT-SP ANT-AVN

540

set

ANT-SP ANT-AVN

90 set

RET-FP RET-AP

5 min

RET-FP RET-AP

3-15 min

RET-FP RET-AP

AVNRT, atrioventricular nodal reentry tachycardia; AVRT, atrioventricular reentry tachycardia; Time, time from intravenous drug administration to termination of arrhythmia; Mode, mode of arrhythmia termination; ANT-SP. termination of arrhythmia because of antegrade block in slow AV nodal pathway; RET-FP, termination of arrhythmia because of retrograde block in fast AV nodal pathway; RET-AP. terminatinn of arrhythmia because of retrograde block in accessory pathway. *This study was not performed during electrophysiologic study

rapid mode of action suggesting a first-pass cardiac effect. The difference in time to termination of arrhythmia between adenosine compounds and verapamil (median 20 vs 80 seconds) is of statistical but probably not clinical significance. The more delayed action (in the range of minutes) of ajmaline, propafenone, and flecainide might be meaningful in rare, very symptomatic patients, yet it is far faster than digoxin. Mode of arrhythmia termination. From the clinician’s point of view, the different modes of arrhythmia termination might be irrelevant as long as the goal of conversion to sinus rhythm is achieved. Yet some aspects related to the site of arrhythmia termination (Table III) might be of more than theoretical importance for patients with antegradely conducting accessory pathways. Termination of PJRT with drugs affecting only the antegrade AV nodal limb might be of importance if atria1 fibrillation should appear either as a spontaneous degeneration of PJRT55-58 or as a proarrhythmic effect of the drugs themselves.47v5g-‘1 This might be particularly relevant when verapamil is used, since precipitation,60* 61 facilitation, and perpetuation5’ of atria1 fibrillation

may occur, with a subsequent verapamil-mediated increased conduction over the accessory pathway potentially leading to malignant ventricular tachyarrhythmias.62* 63 This sequence of events, although theoretically feasible, has yet to be documented (see Addendum). On the other hand, choosing a drug for termination of arrhythmia in the fastconducting retrograde limb (ajmaline, flecainide, or propafenone) might lead to significantly lower rates of success especially in patients with AVRT (Table III). ADVERSEEFFECTS

The cardiac side effects of all antiarrhythmic drugs represent an exaggeration of their intrinsic electrophysiologic and hemodynamic effects. Thus hemodynamic decompensation and bradyarrhythmias resulting from sinus nodal, AV nodal, or infranodal dysfunction are of concern (Table I). Marked sinus bradycardia and AV block are very common after conversion to sinus rhythm with adenosine compounds, but they are usually of no clinical significance since they last just a few seconds.‘“, 21,23,26 Appearance of atria1 and ventricular premature

Volume Number

120 1

beats47p 51 and less commonly precipitation of atrial fibrillation have been reported after the use of verapama47> 59-W 64 and adenosine compounds,“~ I6165 yet precipitation of serious ventricular arrhythmias is far more uncommon.@ 67 Although clinical experience with intravenous diltiazem is limited31, 32*” electrophysiologic and hemodynamic effects comparable to those of verapamil are to be expected.32 Whether any of the proarrhythmic effects commonly attributed to chronic oral therapy with flecainide and propafenone in patients with structural heart disease exist during acute intravenous therapy remains to be determined. Also very common are the noncardiac side effects of adenosine compounds (chest pain, dyspnea, flushing). lo-l43 21-25Transient as they are (subsiding invariably within seconds), they are usually perceived as “minor” by the attending physician. It should be noted, however, that more than half of the patients evaluated with incremental doses of ATP declined to complete a treatment protocol because of these “minor” side effects. 24Taking advantage of the synergistic effects of adenosine compounds with dipyridamole (see below), decreased doses of ATP, with concomitant decreased noncardiac side effects, have been successfully combined with dipyridamole to terminate PJRT. 27 Vomiting has rarely been reported after intravenous propafenone,43 whereas paresthesias, dizziness,36 and transient blurring of vision37 may follow administration of flecainide.3g The list of adverse drug reactions discussed here should be viewed with reservation, since the drugs compared differ significantly with regard to their years of worldwide clinical use. Most of the serious adverse reactions summarized in this report originated in clinical case reports rather than in prospective studies. Thus it is not surprising that more numerous adverse reactions have been noted for the commonly used verapamil than for the more recently introduced drugs flecainide and propafenone. Nevertheless, the clinical spectrum of adverse drug reactions might be of great importance in special circumstances (see below). GUIDELINES FOR THE ACUTE MANAGEMENT OF PJRT Patients with well-tolerated PJRT. This group repre-

sents the majority of patients with PJRT encountered in clinical practice. Virtually any of the previously mentioned drugs might be used for terminating arrhythmia. An important consideration when selecting the antiarrhythmic agent should be the physician’s familiarity with any particular drug. In view of its fairly rapid mode of action, overall excellent efficacy both in terminating and preventing the imme-

Acute management

of

PSVT

183

diate recurrence of arrhythmia, and the rarity of side effects, we consider verapamil the drug of choice for patients with uncomplicated PJRT. For the few patients refractory to verapamil, we use ATP. With this policy we have not encountered difficulties in the conversion of PJRT to sinus rhythm during the last decade. Hemodynamically compromised patients. Patients initially seen with marked hypotension or overt heart failure are at high risk for further hemodynamic deterioration if treated with negative inotropic agents such as calcium channel blockers, ajmaline, flecainide, or propafenone, even if the tachycardia is successfully terminated. These drugs should be contraindicated in these circumstances. Prospective evaluation has shown intravenous verapamil to be safe when given to patients with moderate heart failure (left ventricular ejection fraction >35 % in sinus rhythm); the effective reduction in afterload allegedly safeguards the cardiac index in spite of concomitant negative inotropic effects.6g Nevertheless, a more cautious approach is mandatory for patients with PJRT and signs of overt heart failure. Circulatory collapse70 and serious deterioration of heart failure71 have rarely been reported in adult patients with overt heart failure treated with verapamil. Although administration of intravenous calcium has been shown to prevent7zl 73 and reverse72 the hypotensive effects of intravenous verapamil without affecting its antiarrhythmic properties, adenosine compounds are probably the only safe pharmacologic alternative to immediate direct-current cardioversion for severely hemodynamically compromised patients with PJRT. Infants with PJRT. These patients are usually seen after many hours of persistent tachycardia when signs of hemodynamic decompensation are already evident. Although intravenous verapamil was originally considered safe and effective in terminating PJRT in infants and children,74-76 reports of lifethreatening cardiac decompensation77-80 and deaths1 in infants treated with this drug have led to recommendations against its use in infants altogether,82 or unless it is preceded by intravenous administration of calcium.83 Adenosine and ATP appear to be the drugs of choice for this patient population61 l6 Flecainide has also been safely given to a smaller number of children.343 4o However, the so far more limited use of flecainide dictates against any straightforward recommendations for its use in children. Patients with sick sinus syndrome. These patients should be watched closely for the possibility of bradyarrhythmias developing after termination of PJRT with any drug, especially those affecting sinus node recovery time (Table I). Extreme bradycardia

184

Vi-skin and Belhczssen

requiring temporary pacemaker implantation has been reported even for the very short-acting adenosine.r6 Patients with obstructive pulmonary disease. Special attention should be given to the potential effects of antiarrhythmic agents on the respiratory status of these patients. In view of its vasodilatatory action, intravenous verapamil may abolish hypoxic pulmonary vasoconstriction, leading to increased ventilation/perfusion inequalities, resulting in worsening of preexisting hypoxemia in patients with chronic obstructive lung disease. 84 The resulting decrease in oxygen transport will usually be of no statistical and questionable clinical significance, so that intravenous verapamil is essentially well tolerated when given to this population. 84,85 Of greater concern are the potential detrimental effects of adenosine compounds in patients with lung disease. Adenosine compounds have been found to cause contraction of human bronchial smooth muscle in vitro86 and to induce bronchoconstriction when administered by inhalation to patients with bronchial asthma.87-8g The potential for induction of bronchoconstriction in susceptible patients by intravenous administration is less clear. Continuous intravenous administration of adenosine failed to affect airway reactivity during inhaled metacholine challenge in a recent study of patients with asthma. go Yet adenosine drug levels in this studygo were far below those achieved with the usual dosage for termination of PJRT. A single case report of clinically significant bronchoconstriction induced in a patient with asthma after administration of ATP appears in the French literature.41 We are not aware of any clinically significant adverse effects on the respiratory system being reported during intravenous propafenone. Nevertheless, the intrinsic beta-adrenergic antagonist activity of propafenone and its reported adverse effects in volunteers with asthmag2 are reasons for concern, Thus in view of the vast array of optional effective antiarrhythmic drug therapies available for PJRT, adenosine compounds and propafenone are probably best avoided in patients with evidence of obstructive lung disease and airway hyperreactivity. Pretreatment with antiarrhythmic drugs. Intravenous administration of either verapamil or adenosine compounds is probably safe for patients with therapeutic digoxin blood levels,ll, 48,g3 and yet the former is probably best avoided whenever the possibility of digoxin toxicity exists.” Inasmuch as many patients with PJRT are usually chronically treated with oral verapamil, it is rewarding to know that intravenous verapamil can be administered safely to such patients. g4 Although acute administration of ver-

American

July 1990 Heart Journal

apamil to patients receiving chronic propranolol therapy, who have no signs or symptoms of left ventricular dysfunction or conduction abnormalities, is probably safe,g5 use of antiarrhythmic drugs without significant negative inotropic effects, such as adenosine compounds, is preferable. Rare yet serious hemodynamic decompensation has been reported after intravenous administration of verapamil to patients previously treated with intravenous77 8 or oralg6 beta-adrenergic blockers. Additive blockade of alpha-adrenergic receptors has been blamed for the hypotensive reactions reported in patients treated with oral quinidine and subsequent intravenous verapamiLg7 interaction with other drugs. Dipyridamole inhibits adenosine metabolismg8 by decreasing its cellular uptake. ” Increased side effects with intravenous therapeutic dosages of adenosine have been reported in patients treated with oral dipyridamole.12 On the other hand, methylxanthines such as theophylline are competitive antagonists for adenosine at its cell surface purinoreceptors. loo Thus usual dosages of adenosine may be ineffective in patients treated with theophyl1ine.l’ Propafenone should be used with caution if at all in patients already treated with beta blockers. Although the clinical significance is still unknown, notice should be taken of the potentially important drug interactions of cimetidine, digoxin, and propranolo1 with flecainide.lO Conclusions. A vast array of very effective antiarrhythmic agents offers the attending physician attractive options when choosing a drug for termination of PJRT. This choice should be based on the patient’s clinical characteristics, including any underlying cardiac or noncardiac pathologic conditions, current medications, previous response to therapy, and hemodynamic status. Finally the physician’s familiarity with the use of a particular drug is of primary importance. We believe that for the vast majority of patients who are initially seen with uncomplicated PJRT, verapamil is the drug of choice (Table IV). Although ATP and adenosine are also very effective in terminating PJRT, their common noncardiac side effects, which are frequently uncomfortable, contrast unfavorably with the excellent tolerance of verapamil in this population. Thus we believe that ATP or adenosine should be reserved for cases refractory to a cumulative dose of 10 mg verapamil. The opposite order should be tried in cases in which very rapid conversion of PJRT to sinus rhythm is needed. Although the use of intravenous calcium followed by verapamil is an attractive therapeutic possibility for patients with PJRT and mild hypoten-

Volume Number

120 I

Acute management

of

PSVT

185

IV. Antiarrhythmic drug therapy recommendationsfor acute termination of paroxysmal AV junctional reentrant tachycardia

Table

Patient

First

choice

Second

choice

Verapamil 5-10 mg ATP 5-20 mg Adenosine 2-10 mg

ATP 5-20 mg Adenosine 2-10 mg Calcium * + Verapami15 mg

Infant

ATP/Adenosine 0.04-0.3 mg/kg

Obstructive lung disease

Verapamil Calcium

Calcium + Verapamil (?) Flecainide (?) 1.5 mg/kg/5 min Flecainide Ajmaline 50 mg/3 min

SinusjAV

See text

Uncomplicated

PJRT (adults)

Hemodynamic

decompensation

nodal dysfunction

*Slow intravenous injection of 10

dl

calcium chloride

10

-+

Best avoided

Verapamil (alone) Ajmaline Propafenone Flecainide

ATPlAdenosine Propafenone

gm/dl solution.

sion, we prefer to recommend adenosine compounds if they are available, whereas only the latter should be considered as an alternative to immediate directcurrent cardioversion in cases of more severe decompensation. Verapamil, flecainide, and finally ajmaline should be considered for patients with PJRT and obstructive lung disease. As for infants, ATP and adenosine can probably be used safely. In this population caution should be exercised in choosing the dosage if any of verapamil to be administered and only after infusion of calcium. Finally treatment of PJRT in patients receiving chronic antiarrhythmic drugs or those with known or suspected sinus node or conduction abnormalities should be undertaken only in facilities where emergency cardiac pacing is available, and even then preferably with very short-acting adenosine compounds at reduced initial dosages.

effects or drug interactions. Drugs with a long halflife, such as calcium channel blockers, flecainide, and propafenone, have the potential advantage of preventing an immediate recurrence of the arrhythmia. Adenosine compounds are the fastest acting drugs, resulting in termination of PJRT in less than 30 seconds. The cardiac side effects of all antiarrhythmic drugs represent an exaggeration of their intrinsic electrophysiologic and hemodynamic effects. Thus hemodynamic decompensation and bradyarrhythmias resulting from sinus nodal, AV nodal, or infranodal dysfunction are of major concern. Side effects of adenosine compounds are extremely common but very short lasting. Verapamil is both highly effective and safe except in very special circumstances. Guidelines for therapy of PJRT in specific groups of patients are provided.

SUMMARY

Since submission of this article, important data have been published by Garrat C, et al. In a comparative study of 20 patients undergoing electrophysiologic evaluation for PJRT, adenosine and verapamil had similarly high conversion rates (Am J Cardiol 1989;64:1310-6). More importantly, degeneration of AVRT to rapid preexcited atrial fibrillation after the administration of verapamil, a complication considered “theoreticahy feasible” in our review article, has now been documented (Lancet 1989;2:219).

A vast array of effective antiarrhythmic agents offers the attending physician attractive options for termination of PJRT. Calcium channel blockers, adenosine compounds, amjaline, and the newer drugs flecainide and propafenone offer an efficacy rate of more than 80% for acute termination of PJRT. Choice should be based on the patient’s clinical characteristics including any underlying cardiac or noncardiac pathologic conditions, hemodynamic status, and current medications. Drugs with a very short half-life (adenosine compounds) offer the possibility of repeated administration at increasing dosages or of subsequent administration of a second antiarrhythmic drug without fear of increased adverse

ADDENDUM

REFERENCES

1. Mehta D, Wafa S, Ward DE, et al. Relative efficacy of various physical manoeuvres in the termination of junctional tachycardia. Lancet 1988;1:1181-5.

166

Viskin and Belhassen

L. The clinical use of intravenous verapamil. AM 2. Schamroth HEART J 1980;100:1070-5. 3. Singh BN, Collet JT, Chew CYC. New perspectives in the pharmacological therapy of cardiac arrhythmias. Prog Cardiovasc Dis 1980;22:243-301. 4. Ornato JP. Management of paroxysmal supraventricular tachycardia. Circulation 1986;74(suppl IV):108-10. 5. Klein GJ, Sharma AD, Yee R. An approach to therapy for paroxysmal supraventricular tachycardia. Am J Cardiol 1988:61:77A-82A. 6. Greco R, Musto B, Arienzo V, et al. Treatment of paroxysmal supraventricular tachycardia in infancy, with digitalis, adenosine 5triphosphate. and verapamil: a comparative study. Circulation 1982;66:504-8. I. Benaim ME. Asystole after verapamil [Letter]. Br Med J 1972;2:169-70. CB, Garrard CS, Pickering D. Verapamil in cardiac a. Boothby arrhythmias [Letter]. Br Med d 1972;2:349. 9. Sacks H, Kennelly BM. Verapamil in cardiac arrhythmias [Letter]. Br Med J 1972;2:716. 10. DiMarco JP, Sellers D, Berne RM, et al. Adenosine: electrophysiologic effects and therapeutic use for terminating paroxysmal supraventricular tachycardia. Circulation 1983;68: 1254-63. 11. DiMarco JP, Sellers D, Lerman B, et al. Adenosine: diagnostic and therapeutic use of adenosine in patients with supraventricular tachycardias. J Am Co11 Cardiol 1985;6:41725. 12. Watt AH, Webster BJ, Passani SL, et al. Intravenous adenosine in the treatment of supraventricular tachycardia: a dose-ranging study and interaction with dipyridamole. Br J Clin Pharmacol 1986;21:227-30. 13. Rankin AC, Rae AP, Oldroyd KG, et al. Adenosine or adenosine triphosphate for supraventricular tachycardia? lAbstract1. Circulation 1988:78fsunnl IIl:500. 14. Sellers TD, Kirchhoffer JB, Mohestb TA. Adenosine: a clinical experience and comparison with verapamil for the termination of supraventricular tachycardias. In: Pelleg A, Michelson EL, Dreifus LS, eds. Cardiac electrophysiology and pharmacology of adenosine and adenosine triphosphate. New York: Alan R. Liss, 1987:283-g. E, et al. Rapid and safe termina15. Clarke B, Till J, Rowland tion of supraventricular tachycardia in children with adenosine. Lancet 1987;1:299-301. 16. Overholt ED, Rheuban KS, Gutgesell HP, et al. Usefulness of adenosine for arrhythmias in infants and children. Am J Cardiol 1988;61:336-40. MJ, Linker NJ, Ward DE, et al. Adenosine in the di17. Griffith agnosis of broad complex tachycardia. Lancet 1988;1:672-5. 18. Caruso AC, Miles WM, Klein LS, Zipes DP. Double-blind, placebo-controlled, dose-ranging study of adenosine in patients with supraventricular tachycardia [Abstract]. Circulation 1989;8O(suppl II):II-632. 19. Adenosine Study Group. Adenosine for termination of paroxysmal supraventricular tachycardia: dose ranging and comparison with verapamil. Circulation 1989;8O(suppl II):II631. 20. Greco R, Musto B, Arienzo V, et al. Treatment of paroxysmal supraventricular tachycardia in infancy with digitalis, adenosine 5triphosphate, and verapamil: a comparative study. Circulation 1982;66:504-8. 21. Belhassen B, Pelleg A, Shoshani D, et al. Electrophysiologic effects of adenosine 5-triphosphate on atrioventricular reentrant tachycardia. Circulation 1983;68:827-33. T, Kanaka S, et al. Electrophysiologic 22. Tajima T, Muramatsu effects of intravenous adenosine triphosphate disodium on the paroxysmal supraventricular tachycardias. Jpn Heart d 1985;26:33-43. 23. Saito D, Ueeda M, Abe Y, et al. Treatment of paroxysmal supraventricular tachycardia with intravenous injection of adenosine triphosphate. Br Heart J 1986;55:291-4. 24. Sharma AD, Klein GJ. Comparative quantitative electro-

American

25

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

36. 37.

38.

39.

40.

41.

42.

43.

44.

July 1990 Heart Journal

physiologic effects of adenosine triphosphate on the sinus node and atrioventricular node. Am J Cardiol 1988;61:330-5. Belhassen B, Glick A, Laniado S. Comparative clinical and electrophysiologic effects of adenosine triphosphate and verapamil on paroxysmal reciprocating junctional tachycardia. Circulation 1988;77:795-805. Cabrera-Sole R, Abeytua M, Lopez Bescos L, Rubio R. Treatment of paroxysmal supraventricular tachycardia: adenosine triphosphate vs verapamil. Circulation 1989; 8O(suppl II): 11.632. Kikushima S, Kobayashi Y, Tanno K, et al. Efficacy of adenosine triphosphate-dipyridamole combination therapy on supraventricuiar tachycardia. Circulation 1989;8O(suppl II):II-632. Sethi KK, daishnkar S, Gupta MP. Salutary effects of intravenous ajmaline in patients with paroxysmal supraventricular tachycardia mediated by dual atrioventricular nodal pathways: blockade of the retrograde fast pathway. Circulation 1984;70:876-83. Belhassen B, Pelleg A, Geva B, et al. Electrophysiologic effects of ajmaline in AV nodal reentrant tachycardia. In: Feruglio GA, ed. Cardiac pacing, electrophysiology and pacemaker technology. Padova: Piccin Medical Books, 1982: 261-6. Rowland E, McKenna WJ, Krikler DM. Eiectrophysiologic and antiarrhythmic actions of bepridil. Comparison with verapamil and ajmaline for atrioventricular reentrant tachycardia. Am J Cardiol 1985;55:1513-9. Rozanski JJ, Zaman L, Castellanos A. Electrophysiologic effects of diltiazem hydrochloride on supraventricular tachycardia. Am J Cardiol 1982;49:621-8. Huycke EC, Sung RJ, Dias VC, et al. Intravenous diltiazem for termination of reentrant supraventricular tachycardia: a placebo-controlled, randomized, double-blind, multicenter study. J Am Co11 Cardiol 1989;13:538-44. Jackman WM, Friday KJ, Dias VC. Dose response study of IV diltiazem for termination of supraventricular tachycardia. Circulation 1989;8O(suppl II):II-632. Ward DE, Jones S, Shinebourne EA. Use of Aecainide acetate for refractory junctional tachycardias in children with the Wolff-Parkinson-White syndrome. Am J Cardiol 1986; 57:787-90. Crozier IG, Ikram H, Kenealy M, et al. Flecainide acetate for conversion of acute supraventricular tachycardia to sinus rhythm. Am J Cardiol 1987;59:607-9. Hellestrand KJ. Intravenous flecainide acetate for supraventricular tachycardias. Am J Cardiol 1988;62:16D-22D. Lacombe P, Cointe R, Metge M, et al. Intravenous Aecainide in the management of acute supraventricular tachyarrhythmias. J Electrophysiol 1988;2:19-22. Neuss H, Schlepper M. Long-term efficacy and safety of flecainide for supraventricular tachycardia. Am .J Cardiol 1988;62:56D-61D. Anderson JL, Jolivette DM, Fredell PA. Summary of efficacy and safety of flecainide for supraventricular arrhythmias. Am J Cardiol 1988;62:62D-66D. Musto B, D’Onoofrio A, Cavallaro C, et al. Electrophysiologic effects and clinical efficacy of flecainide in children with recurrent paroxysmal supraventricular tachycardia. Am J Cardiol 1988;62:229-33. Shen EN, Keung E, Huycke E, et al. Intravenous propafenone for termination of reentrant supraventricular tachycardia. Ann Intern Med 1986;105:655-61. Hammill SC, McLaran CJ, Wood DL, et al. Double-blind study of intravenous propafenone for paroxysmal supraventricular reentrant tachvcardia. J Am Co11 Cardiol 1987:9: 13648. Ludmer PL, McGowan NE, Antman EN, et al. Efficacy of propafenone in Wolff-Parkinson-White syndrome: electrophysiologic findings and long-term follow-up. J Am Co11 Cardiol 1987;9:1357-63. Dubuc M, Kus T, Campa MA, et al. Electrophysiologic

Volume

120

Number

1

45. 46.

41. 48.

49.

50.

51.

effects of intravenous propafenone in WPW syndrome. AM HEART J 1989;117:370-6. Manolis AS, Estes NAM. Supraventricular tachycardia. Mechanisms and therapy. Arch Intern Med 1987;147:170616. Bexton RS, Hellestrand KJ, Nathan AW, et al. A comparison of the antiarrhythmic effects on AV junctional re-entrant tachycardia of oral and intravenous flecainide acetate. Eur Heart J 1983;4:92-102. Sung RJ, Elser B, McAllister RG. Intravenous verapamil for termination of re-entrant supraventricular tachycardias. Ann Intern Med 1980;93:682-9. Waxman HL, Myerburg RJ, Appel R, et al. Verapamil for control of ventricular rate in paroxysmal supraventricular tachycardia and atria1 fibrillation or flutter. Ann Intern Med 1981;94:1-6. Wellens HJJ, Tan SL, B&r FWH, et al. Effect of verapamil studied by programmed extrastimulation of the heart in patients with paroxysmal re-entrant supraventricular tachycardia. Br Heart J 1977;39:1058-66. Rinkenberger RL, Prystowsky EN, Heger JJ, et al. Effects of intravenous and chronic oral verapamil administration in patients with supraventricular tachyarrhythmias. Circulation 1980;62:996-1010. Hamer A, Peter T, Platt M, et al. Effects of verapamil on supraventricular tachycardia in patients with overt and concealed Wolff-Parkinson-White syndrome. AM HEARTJ

1981;101:600-12. 52. Klein GJ, Gulamhusein S, Prystowsky EN, et al. Comparison of electrophysiologic effects of intravenous and oral verapamil in patients with paroxysmal supraventricular tachycardia. Am J Cardiol 1982;49:117-24. 53. Hamer A, Peter T, Mandel W. Atrioventricular node reentry: intravenous verapamil as a method of defining multiple electrophysiologic types. AM HEARTJ 1983;195:629-42. 54. Tai DY. Charm MS. Svinarich JT. et al. Mechanisms of verapamil-induced conduction block in anomalous atrioventricular bypass tracts. J Am Co11 Cardiol 1985;5:311-7. 55. Schamroth L, Krikler DM. The problem of lone atrial fibrillation. S Afr Med 1967;41:502-4. 56. Klein GJ, Bashore TM, Sellers TD, et al. Ventricular fibrillation in the Wolff-Parkinson-White syndrome. N Engl J Med 1979,301:1080-5. 57. Sung RJ, Castellanos A, Mallon SM, et al. Mechanisms of spontaneous alternation between reciprocating tachycardia and atria1 flutter-fibrillation in the Wolff-Parkinson-White syndrome. Circulation 1977;56:409-16. 58. Wyndham CRC, Amat-y-Leon F, Wu D, et al. Effects of cycle length on atria1 vulnerability. Circulation 1977;55:260-7. 59. Harper RW, Whitford E, Middlebrook K, et al. Effects of verapamil on electrophysiologic properties of the accessory pathway in patients with the Wolff-Parkinson-White syndrome. Am J Cardiol 1982;50:1323-30. 60. Falk RH, Knowlton AA, Manaker S. Verapamil induced atria1 fibrillation [Letter]. N Engl J Med 1988318:640-l. 61. Belhassen B, Viskin S, Laniado S. Sustained atria1 fibrillation after conversion of paroxysmal reciprocating junctional tachycardia by intravenous verapamil. Am J Cardiol 1988;62:835-7. 62. Gulamhusein S, Ko P, Klein GJ. Ventricular fibrillation following verapamil in the Wolff-Parkinson-White syndrome.

Acute management of PSVT

67. 68.

69.

70. 71.

12. 73. 74. 75. 76. 77. 78. 79. 80. 81.

82. 83. 84. 85. 86.

AM HEARTJ 1983;106:145-7. 63. McGovern B, Garan H, Ruskin JN. Precipitation of cardiac arrest bv verauamil in patients with Wolff-Parkinson-White syndrome. Ann Intern-Med 1986;104:791-4. 64. Heng MK, Singh BN, Roche AHG, et al. Effects of intravenous verapamil on cardiac arrhythmias and on the electrocardiogram. AM HEARTJ 1975;90:487-98. 65. Belhassen B, Pelleg A, Shoshani D, et al. Atria1 fibrillation induced by adenosine triphosphate. Am J Cardiol 1984; 53:1405-6. 66 Vohra J, Peter T, Hunt D, et al. Verapamil induced prema-

87. 88. 89. 90.

187

ture ventricular beats before reversion of supraventricular tachycardia. Br Heart J 1974;36:1186-93. Winters SL, Schweitzer P, Kupersmith J, et al. Verapamilinduced p.olymorphous ventricular tachycardia. J Am Co11 Cardiol 198$6:257-g. Betriu A, Chaitman BR, Bourassa MG, et al. Beneficial effect of intravenous diltiazem in the acute management of paroxysmal supraventricular tachycardias. Circulation 1983;67:8894. Klein HO, Ninio R, Oren V, et al The acute hemodynamic effects of intravenous verapamil in coronary artery disease: assessment by equilibrium-gated radionuclide ventriculography. Circulation 1983;67:101-10. Opie LH. Calcium antagonists. Lancet 1980;1:806-9. Chew CYC, Hecht HS, Collet JT, et al. Influence of severity of ventricular dysfunction on hemodynamic responses to intravenously administered verapamil in ischemic heart disease. Am J Cardiol 1981;47:917-23. Weiss AT, Lewis BS, Halon DA, et al. The use of calcium with verapamil in the management of supraventricular tachyarrhythmias. Int J Cardiol 1983;4:275-80. Haft JI, Habhab MA. Treatment of atria1 arrhythmias. Effectiveness of verapamil when preceded by calcium infusion. Arch Intern Med 1986:146:1085-9. Porter CBJ, Gillette PC, Garson Jr A, et al. Effects of verapamil on supraventricular tachycardia in children. Am J Cardiol 1981;48:487-92. Soler-Soler J, Sagrista-Sauleda J, Cabrera A. et al. Effect of verapamil in infants with paroxysmal supraventricular tachycardia. Circulation 1979;59:876-9. Porter CJ, Garson Jr A, Gillette PC. Verapamil: an effective calcium blocking agent for pediatric patients. Pediatrics 1983:71:748-55. Abinader E, Borochowitz Z, Berger A. Hemodynamic decompensation of verapamil therapy in a neonate. Helv Paediatr Acta 1981;36:451-5. Leitner RP, Hawker RE, Celermajer JM. Intravenous verapamil in the treatment of paroxysmal supraventricular tachycardia in children. Aust Paediatr J 1983;19:40-4. Radford D. Side effects of verapamil in infants. Arch Dis Child 1983;58:465-6. Epstein ML, Kiel EA, Victoria BE. Cardiac decomuensation following verapamil therapy in infants with supraventricular tachvcardia. Pediatrics 1985;75:737-40. Garland JS, Berens RJ, Losek JD, et al. An infant fatality following verapamil therapy for supraventricular tachycardia: cardiovascular collapse following intravenous verapamil. Pediatr Emerg Care 1985;1:198-200. Garson A. Medicolegal problems in the management of cardiac arrhythmias in children. Pediatrics 1987;79:84-8. Roguin N, Shapir Y, Blazer S, et al. The use of calcium gluconate prior to verapamil in infants with paroxysmal supraventricular tachycardia. Clin Cardiol 1984;7:613-6. Hazard PB, Burnett CR. Verapamil in multifocal atria1 tachycardia. Hemodynamic and respiratory changes. Chest 1987;91:68-70. Berman BA, Ross RN. Treating coexisting cardiovascular and pulmonary disease with calcium antagonists. Ann Allergy 1986;56:195-200. Holgate ST, Mann JS, Cushley MJ. Adenosine as bronchoconstriction mediator in asthma and its antagonism by methyl-xanthines. J Allergy Clin Immunol 1984;74:302-6. Cushley MJ, Tattersfield AE, Holgate ST. Adenosine-induced bronchoconstriction in asthma. Am Rev Respir Dis 1984;129:380-4. Holgate ST, Mann JS, Church MK, et al. Mechanisms and significance of adenosine-induced bronchoconstriction in asthma. Allergy 1987;42:481-4. Crimi N, Palermo F, Oliveri R, et al. Enhancing effect of dipyridamole inhalation on adenosine-induced broncho_^^^ spasm in asthmatic patients. Allergy lY88;43:179-83. Larsson K, Sollevi A. Influence of infused adenosine on

July 1990

Viskin and Belhassen

91.

92.

93.

94.

95.

American

bronchial tone and bronchial reactivity in asthma. Chest 1988;93:280-4. Taviot B, Pacheco Y, Coppere B, et al. Bronchospame induit par l’injection d’adenosine chez un asthmatique [Letter]. Presse Med 1986;15:1103. Hill MR, Gotz VO, Harman E, et al. Evaluation of the asthmogenicity of propafenone, a new antiarrhythmic drug. Comparison of spirometry with metacholine challenge. Chest 1986;90:698-702. Frishman WH, LeJemtel TH. Electropharmacology of the slow-channel inhibitors in the management of cardiac arrhythm&: verapamil. PACE 1982;5:402-13. Pritchett ELC, Reiter MJ, Hammill SC, et al. Is it safe to use intravenous verapamil to treat a patient who is taking oral verapamil? AM HEART J 1983;105:329-31. Reddy PS, Uretaky BF, Steinfeld M. The hemodynamic effects of intravenous verapamil in patients on chronic propranolol therapy. AM HEART J 1984;107:97-101.

Report

Yuzo Hirota, MD, Gen Shimizu, MD, Yoshio Kita, MD, Yasushi Nakayama, Michihiro Suwa, MD, Keishiro Kawamura, MD, Seiki Nagata, MD, Toshitami Sawayama, MD, Toru Izumi, MD, Takeshi Nakano, MD, Hironori Toshima, MD, and Morie Sekiguchi, MD. Suita,

Kurashiki,

Niigata,

Tsu, Kurume,

There are three types of idiopathic cardiomyopathy: hypertrophic, dilated, and restrictive. Restrictive cardiomyopathy (RCM) is the least common and most obscure disease. The report of the WHOLISFC task force does not include a definition of this disease or diagnostic criteria.l Restrictive physiology resulting from disposition of amyloid or hemosiderin is well

From the Third Division, Department of Internal Medicine, Osaka Medical College; the Department of Internal Medicine, The National Cardiovascular Center; the Department of Cardiology, Kawasaki Medical College; the First Department of Internal Medicine, Niigata University Medical School; the First Department of Internal Medicine, Mie University Medical School; the Third Department of Internal Medicine, Kurume University Medical School; and the Department of Internal Medicine, Japan Heart and Blood Pressure Institute, Tokyo Women’s Medical College. Supported by a grant from the Ministry of Health and Welfare of the Japanese Government for the study of cardiomyopathy. ’ Received for publication Jan. 12, 1990; accepted Feb. 26, 1990. Reprint requests: Yuzo Hirota, MD, Third Division, Department of Internal Medicine, Osaka Medical College, 2-7 Daigdmcho, Takatsuki City, Osaka

569, Japan.

4/ 1120484

188

Journal

DM, Spurrell RAJ. Verapamil in the treatment of 96. Krikler paroxysmal supraventricular tachycardia. Postgrad Med J 1974;50:447-53. HJ, Insel PA. Hypotension after quini97. Maisel AS, Motulsky dine plus verapamil. N Engl J Med 1985;312:167-70. EE. Dipyridamole inhibition of adenosine metab98. Klabunde olism in human blood. Eur J Pharmacol 1983;93:21-6. 99. Kolassa N, Pfleger K, Rummel W. Specificity of adenosine uptake into the heart and inhibition by dipyridamole. Eur J Pharmacol 1970;9:265-8. 100. Bruns RF, Daly JW, SnyderSH. Adenosine receptor binding structure-activity analysis generates extremely potent xanthine antagonists. Proc Nat1 Acad Sci 1983;80:2077-80. 101. Roden DM, Woosley RL. Drug therapy. Flecainide. N Engl J Med 1986;315:36-41.

Spectrum of restrictive cardiomyopathy: of the national survey in Japan

Takatsuki,

Heart

and Tokyo,

MD,

Japan

known as amyloid heart disease or cardiac hemochromatosis.2 Another type of heart disease that causes restrictive physiology includes endomyocardial fibrosis as the sequela of tropical or nontropical hypereosinophilia or endocardial fibroelastosis.2 These diseases, however, should be classified as specific diseases of the heart muscle, inasmuch as associations or causes are known. Idiopathic RCM can be defined as disease of the heart muscle as indicated by reduced myocardial compliance of unknown cause. Although numerous reports have been published recently describing the diastolic properties and differential diagnosis of RCM and constrictive pericarditis,3-10 almost all cases were specific heart muscle disease of restrictive physiology. The clinical profiles and natural history of idiopathic RCM are not well established. This study was undertaken to clarify the incidence, clinical profile, natural history, and hemodynamic characteristics of idiopathic RCM by means of a nationwide questionnaire survey in Japan.