Termination of tachycardias by interrupting blood flow to the arrhythmogenic area

ARRHYTHMIAS AND CONDUCTION DISTURBANCES

Termination of Tachycardias by Interrupting Blood Flow to the Arrhythmogenic Area

Pedro Brugada, MD, Hans de Swart, MD, Joep L.R.M. Smeets, MD, Frits W.H.M. Bar, MD, and Hein J.J. Wellens, MD

The hypothesis that production of ischemia or cooling of an arrhythmogenic area or pathway could interrupt tachycardias was tested by subseleetive catheterization of the coronary artery supplying the site of origin of ventricular tachycardia (9 patients), the accessory pathway (2 patients) and the site of origin of atrial tachycardia (1 patient). Ventricular tachycardia was reproducibly terminated and reinduction temporarily prevented in 8 of the 9 patients by occlusion of the artery or administration of iced isotonic saline. Block in the accessory pathway was obtained in 1 of the 2 patients with Wolff- Parkinson-White syndrome. Selective cooling through the atrioventricular nodal artery in 1 patient terminated his circus movement tachycardia. Reproducible termination of a continuous atrial tachycardia was obtained by cooling of the atrial branch supplying the site of origin of the arrhythmia. These data demonstrate the feasibility of iden- tification and selective catheterization of the coronary artery branch supplying blood to an arrhythmogenic area or pathway and suggest a new possibility for treatment of tachycardias by perma- nently blocking the blood supply to the site of origin or pathway of a tachycardia.

(Am J Cardiol 1988;62:387-392)

From the Department of Cardiology, Academic Hospital, University of Limburg, Maastricht, The Netherlands. Manuscript received March 4, 1988; revised manuscript received and accepted May 6, 1988.

Address for reprints: Pedro Brugada, MD, Clinical Electrophysiol- ogy Laboratory, Department of Cardiology, Academic Hospital, Maas- tricht, The Netherlands.

T achycardias can be treated by drugs, surgery, electrical pacemakers, cardioverters, defibrillators, electrical or chemical ablation.te6 Surgery and

ablation are the only forms of treatment that destroy the tachycardia substrate and result, when successful, in definitive cure of the arrhythmia.

Any arrhythmogenic area or pathway in the heart requires blood supply. Ventricular tachycardia (VT) in scars after myocardial infarction seems to be based on slow conduction and reentry in strands of surviving cells.7s Sufficient blood supply is necessary for the maintenance of the electrical properties of those cells. Adequate blood supply is also required to the accessory atrioventricular pathway if this structure is involved in Wolff-Parkinson-White syndrome (WPW) arrhythmias and to areas responsible for atria1 tachycardia. The pur- pose of the present study was to determine whether in- terruption of arterial blood supply or administration of iced saline to arrhythmogenic areas or pathways could acutely interrupt tachycardias.

METHODS Patients: Twelve patients were studied. All gave in-

formed consent. Five patients had paroxysmal recurrent VT after a myocardial infarction. Three patients had daily continuous episodes of VT also after a myocardial infarction. One patient experienced continuous VT and had no identifiable structural heart disease (idiopathic VT). Two patients had WPW syndrome and paroxysmal circus movement tachycardia using retrogradely the accessory atrioventricular pathway. One patient had continuous left atria1 tachycardia, probably present since birth.

Electrophysiologic study: Using previously de- scribed methods,9 an electrophysiologic study was performed in all patients to confirm the site of origin of tachycardia and to map the earliest site of endocardial activation during VT or atria1 tachycardia.*O The site of origin of VT was further confirmed by the location of myocardial infarction, results from pace mapping and the morphology of the QRS complex and axis during the arrhythmia. to-l2 The morphology of the delta wave showing maximal preexcitation, shortest atria1 stimulus delta interval during atria1 pacing and the earliest site of atria1 activation during circus movement tachycardia were used to localize the accessory pathway in the 2 patients with WPW syndrome. Endocardial atria1 mapping identified the site of origin of atria1 tachycardia. Data from intraoperative epi- and endocardial mapping during arrhythmia surgery confirmed in 1 patient with

THE AMERICAN JOURNAL OF CARDIOLOGY SEPTEMBER 1, 1988 387

TRANSCORONARY TERMINATION OF TACHYCARDIAS

FIGURE 1. Transient termination of contim~~s atria1 tachycardia by administration of iced saline through dective &heterk- tionof(Ikftatrialbranehariringfromthedi~partoftherigM coronaryartery.Fiisurfaceleadsareshownsim~ with an aortic pressure tracing. Continuous atrial tachycardia is obserd on the right. Note the negative P wave in lead aVl. in; ~ngthelettatrialoriginoftheanlrythmia.Thetachyeardiatr~terminateotoraboutJreeondrattheendoftheieed sahe injedion and reinitiates spontaneously thereafter. T = l-second time mark.

FlGURE 2. A, dective catheter- lzatlonofaseptallnwnch(right ~~~Pd=t&njv Iwo-

blood supply (mrowhemds) to thedb3talpartoftheligtltcoro- nary arlery (sfrows). The open 8WOWpOilltStOth6+llW&lllIld-

er of the 2SFr catheter. B, ter- minatienof ventdab tachycar- diadudng8tim~atjlmof10 llllofiCeddlle.FoUSWfaCe eketrowdiographieleadsare simuftaneourfy-wlth theaadlcpressure.

388 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 62

VT, the 2 patients with WPW syndrome and the patient with continuous atria1 tachycardia the preopera- tively determined site of origin of the arrhythmias or the location of the accessory pathway. At the time of study, 3 patients with continuous VT after myocardial infarction were receiving antiarrhythmic drugs (amiodarone and propafenone). The other patients were free from medication.

Site of origin of tachycardias and location of the accessory pathways: The arrhythmia originated in the border zone of the infarction in all patients with VT after myocardial infarction. These areas were septally located in 5 patients, in the inferior wall in 2 and in the posterior wall in the remaining patient. Multiple mor- phologies of VT were induced in all 8 patients. Accord- ing to endocardial mapping, pace mapping and arrhythmia morphology and axis, different exit points could have been responsible for the different arrhythmia mor-

phologies originating in the same areas.” VT originated high in the inter-ventricular septum in the patient with idiopathic VT. The accessory pathway was located in the left ventricular free wall in both patients with WPW syndrome. In the patient with continuous atria1 tachycardia the arrhythmia originated in the left atria1 appendage.

Production of ischemia or intermption of blood supply to arrhythmogenic areas or pathways by cold saline: Once the sites of origin of tachycardias or locations of the accessory pathways were determined, their blood supply was studied using coronary angiography. Coro- nary angiography was performed using the Judkins technique. Special care was taken to identify coronary arteries supplying collateral flow to areas of myocardial infarction in patients with VT. In patients with an accessory pathway and in the patient with continuous atrial tachycardia, the artery thought to supply the site of

FtGURE 3. A, in this right anterior cbllcps projsctlon, the 2dFr cathe!tsr (open amwj has be!on advanced to the! distal portii of the poddor doswndhg coronary artary, giving cokttd nowtothedistalpartoftheleR

loads are shown. B I i L / i. / 1. / “_.. ! ,86024 I WC

mmHgO I

II

III

avr

avl

avf

THE AMERICAN JOURNAL OF CARDIOLOGY SEPTEMBER 1. 1988 389

TRANSCORONARY TERMINATION OF TACHYCARDIAS

the accessory pathway and the left atria1 appendage was identified.

An injection of isotonic iced saline (approximate temperature 2°C) was first given in the proximal right or left coronary artery. Selective catheterization of the coronary artery supplying the arrhythmogenic area or pathway was performed thereafter using a 2SFr catheter introduced through a steerable guidewire (0.014 inch) using standard percutaneous transluminal coronary angioplasty techniques. Once selective catheterization of the coronary artery was done, the catheter was used to occlude coronary flow or to inject iced saline during tachycardias. Ten ml of iced isotonic saline was given through the 2.5Fr catheter over a 2- to 4-second period. Reinduction of tachycardias was attempted during occlusion of the coronary artery and immediately after termination of tachycardias by cooling.

RESULTS Acute termination of tachycardias by ischemia or

iced saline: Selective catheterization and perfusion of iced saline in the proximal right or left main coronary arteries did not result in termination of tachycardias or conduction block over the accessory pathway except in the patient with idiopathic VT, in whom isotonic saline injected in the left main coronary artery (but not in the right coronary artery) reproducibly terminated the arrhythmia. Subselective catheterization and occlusion or perfusion of iced saline in the circumflex coronary artery resulted in termination of VT in the patient with continuous VT arising from a posterior wall myocardial infarction. Injection of iced saline in the circumflex coronary artery also resulted in anterograde conduction

block over the accessory pathway in 1 of the 2 patients with preexcitation.

Selective catheterization and occlusion or injection of iced saline through the distal right coronary artery supplying the left atria1 site of origin reproducibly terminated continuous atria1 tachycardia (Figure 1). Cir- cus movement tachycardia was terminated during selective catheterization of the atrioventricular nodal artery in 1 patient. VT was terminated in 8 of the 9 patients (Figures 2, 3 and 4). In 1 patient with VT the morphology of the arrhythmia could be reproducibly changed but not terminated (Figure 5). Tachycardias could therefore be reproducibly terminated in 10 of the 11 patients in whom this was attempted. In each patient tachycardia was terminated at least twice with selective cooling. In 1 patient a total of 16 episodes of VT was terminated by selective cooling.

Blood supply to the arrhythmogenic area in patients with ventricular tachycardia: In the patient with a posterior wall myocardial infarction, a reperfused ste- nosed (80%) circumflex coronary artery supplied the area of myocardial infarction and the site of origin of the arrhythmia. Injection of iced saline in the distal part of this artery before the stenosis reproducibly terminated the arrhythmia. Of the 2 patients with inferior wall myocardial infarction, 1 had normal coronary arteries and myocradial infarction had developed years before as a result of spasm of the right coronary artery during coronary angiography. VT morphology could be changed in this patient, but the arrhythmia did not terminate during occlusion or cooling through the posterior descending coronary artery (Figure 5). In the other patient with inferior wall myocardial infarction, collateral


FIGURE 4. A, the septal branch (arrows) is shown catheteriwd (right) with the 2SFr catheter (open amwj in this left anterior oblique projedii. B, ternha- tlon of ventricular tachycardii by adminstration of iced saline. Flve swface loads are shown.

supply to the posterior descending coronary artery (Fig- ure 2) came from a septal branch of the left anterior descending coronary artery. Collateral supply to the left anterior descending coronary artery from the posterior descending right coronary artery was present in 2 of the 3 patients with anterior wall myocardial infarction and from an obtuse marginal branch in the remaining patient. VT was reproducibly terminated by administration of iced saline through the posterior descending coronary artery (Figure 3) or the obtuse marginal branch. In the remaining 2 patients with anterior and inferior wall myocardial infarction, a patent septal branch took off just before an occluded left anterior descending coronary artery. VT was reproducibly terminated by cooling through that septal branch (Figure 4). In the patient with continuous idiopathic VT, occlusion or administration of iced saline through the conus branch from the right coronary artery had no effect on VT. The arrhythmia was reproducibly terminated by administration of iced saline on the left main coronary artery and through the first septal branch of the left anterior descending coronary artery.

Relation between site of origin and morphology of ventricular tachycardia and artery allowing termination of the arrhythmia by selective cooling: A surpris- ing finding in this study was the ability to terminate by

FIGURE 5. changes in axis and mer- zyol vontrlcular lmhycardii in-

ocdudonofthedistelright cormmfyarteryintbepatiiinwbem vm Wycartga cculd net be terminated.Tbe3panekrhowacen- tinwus registration of 5 surface elec- trocardbgraphicleadsandlhopros- sure-lnthodistalpartofthe calhotor wedgod on lhe ItgIlt comnaly artery. A, the dinical tachycardta is obeorvedinthsfiret~ofthotop panel. Then the twhycardii changes its axis and accelerates dtring ecdu- sienoftbearteryandbecemeepdy- morphic tater em (B). Finally, the arrhythmia becomes monomorphic again (CJ. The tachycardia was terminated by overdrive pacing at that time.

A

iced saline VTs apparently originating far from the visible collateral blood supply. These observations were made in 3 of the 4 patients without a patent infarct- related vessel. As shown in Figure 3, a VT originating in the superior septum was terminated by administration of iced saline through the posterior descending coronary artery giving visible collateral supply to the distal left anterior descending coronary artery. In 2 other patients, VT originating in the distal septum could be terminated by administration of iced saline through a proximal septal branch. These findings could suggest that the effects of iced saline reached further than the visible collateral blood supply owing to the insufficient resolution properties of our present radiologic equip- ment to identify very small coronary arteries, or that a large reentry circuit was responsible for the arrhythmia.

Duration of the effects of iced saline and ischemia: Iced saline transiently terminated tachycardia in 2 patients with continuous VT and in the patient with continuous atria1 tachycardia (Figure 1). The arrhythmia resumed after a few seconds. The same was observed after transient (30 seconds) occlusion of the coronary artery. The effects of longer lasting occlusion of the coronary artery were not assessed in these 3 patients.

In the remaining patients with VT in whom ischemia or iced saline reproducibly terminated the arrhyth-

THE AMERICAN JOURNAL OF CARDIOLOGY SEPTEMBER 1. 1988 391

TRANSCORONARY TERMIidATION OF TACRYCARMAS

mia, a longer lasting (2 to 15 minutes) occlusion of the coronary artery prevented reinduction of the arrhythmia by pacing techniques that had reproducibly initiat- ed tachycardia before inducing ischemia to the arrhythmogenic area. Long lasting occlusion of the coronary artery supplying blood to the accessory pathway was not attempted in either of the 2 patients with WPW syndrome.

Complications: During catheterization of the right coronary artery, 1 patient developed spasm that re- sponded to nitroglycerin without further consequences. Injection of saline resulted in light chest pain in 1 patient. Iced saline changed the morphology of VT in 1 patient but did not terminate it. A decrease in blood pressure in this patient necessitated overdrive pacing to terminate the arrhythmia. No significant increase in en- zyme values occurred in any patient following tempo- rary occlusion.

DISCUSSION This study demonstrated that it is possible to identi-

fy a distal coronary artery providing blood supply to arrhythmogenic areas or pathways. Induction of ischemia by occluding that coronary artery or the injection of iced saline can change the electrophysiologic properties of the arrhythmogenic area or pathways and acutely terminate and transiently prevent the occurrence of the arrhythmias. These data suggest that use of the re- fined percutaneous transluminal coronary angioplasty techniques presently available makes possible a selective catheterization of small coronary arteries to interrupt blood supply to the arrhythmogenic foci or pathways in the human heart. If a safe and reproducible method to transcoronarily ablate the arrhythmogenic areas or pathways can be developed, the major advantage would be that treatment is directed to the arrhythmia substrate without affecting the rest of the heart. If conduction’in the accessory pathway in patients with preexcitation can selectively be blocked, arrhythmias using that pathway will no longer be possible. Similarly, when the site of origin of VT is ablated, the VT can no longer occur.

Application of our findings to the treatment of ventricular and supraventricular arrhythmias will require further investigation. However, these data, like the ex-

perimental findings recently reported by Inoue et a1,6 suggest a new concept in the treatment of arrhythmias in human beings. The main challenges for its further development are clear. First, although the percutaneous transluminal coronary angioplasty techniques presently available allowed us to selectively catheterize arteries with a lumen of approximately 1 mm, when definitive ablation (for instance, chemical) of an arrhythmogenic area or pathway is considered, the damage to the myo- cardium will have to be as limited as possible. Adminis- tration of iced saline allows “mapping” of the arterial blood supply to the arrhythmogenic area or pathways. Its specificity will have to be demonstrated in a larger number of patients by selecting catheterizing arteries thought to be related (or not) to the arrhythmogenic area or pathway.

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Termination of tachycardias by interrupting blood flow to the arrhythmogenic area