ARRHYTHMIAS AND CONDUCTION DISTURBANCES

Cryoablation of Refractory Sustained Ventricular Tachycardia Due to Coronary Artery Disease Jose Caceres, MD, Masood Akhtar, MD, Paul Werner, MD, Moharnmad Jazayeri, MD,

James McKinnie, MD, Boaz Avitall, MD, and Patrick Tchou, MD

Thirty-nine patients with medically refractory sus- tained monomorphic ventricular tachycardia (VT) due to coronary artery disease underwent map- guided cryosurgery. Locations of prior myocardial infarctions had been inferior in 22, anterior in 16 and combined in 1. Mean age was 61 f 9 years and the mean number of drug trials per patient be- fore surgery was 3.8 f 1.4. lntraoperative endo- cardiai mapping induced 67 tachycardias in 35 pa- tients. Each patient received 6 to 18 (11 f 3) endo- cardiai cryothermic applications (15 mm, -6O”C, 2 minutes) at areas of earliest activation during VT. Encircling endocardial cryoabiation was performed in 4 patients who had unsuccessful mapping. In ad- dition, 11 patients had subendocardial resection of their well-demarcated septai scars as well as cryo- surgery. There were 2 in-hospital deaths. At post- operative programmed ventricular stimulation, 28 of the 37 patients (76%) had no inducible or spon- taneous VT before hospital discharge. Six patients (16%) with spontaneous or inducible VT had a sln- gie morphology and were controlled with antiar- rhythmic drugs that had previously failed. There- fore, surgery alone or in combination with drugs was efficacious in 92% of the population surviving surgery. The remaining 3 patients (9%) received automatic implantable cardioverter defibrillators. No significant difference in surgical outcome was seen between patients who had cryosurgery alone and those who had subendocardiai resection to- gether with cryoablation. Mean left ventricular ejection fractions before and after surgery were 33 and 39%, respectively (p <O.Ol). Clinical follow-up ranged from 2 to 36 months (1B f 12). One patient died of heart failure and another underwent heart transplantation. No recurrence of sustained VT, cardiac arrest, syncope or defibrillator discharge has occurred in the remaining patients. -Thus, cryoablation was highly effective and should be considered as a good alternative to subendocardiai resection in patients with drug-resistant sustained VT related to coronary artery disease.

(Am J Cardioi 1989;63:296-300)

lectrophysiologically guided surgical ablation E is of proven value in medically refractory sustained monomorphic ventricular tachycardia (VT) due

to coronary artery disease.1*2 Surgical techniques in- clude encircling endocardial ventriculotomy,3 subendo- cardial resection4 encircling endocardial cryoablation5 and laser photoablation. Localized subendocardial re- section has been the most commonly used approach and its surgical success rate is in the 60 to 70% range.7,8 Extensive endocardial resection alone or in combination with cryoablation has further improved the surgical cure rate in some series.2,g However, in ventricular tachycardias with earliest sites of activation outside the visible scar, subendocardial resection alone has not been effective.2 Although cryosurgery in this setting seems to be a good alternative, 5,10 the efficacy of this procedure as the sole ablative technique for sustained monomor- phic VT due to coronary artery disease has been un- clear. In the present report, we evaluated the periopera- tive and long-term results of map-guided cryosurgery as the primary ablative procedure in patients with drug- resistant VT related to coronary artery disease.

METHODS Study patients: Between January 1985 and Febru-

ary 1988, 39 consecutive patients with documented cor- onary artery disease and recurrent VT refractory to multiple antiarrhythmic drugs underwent cryosurgery as the primary ablative procedure for their arrhythmias. All patients had spontaneous presentation of VT associ- ated with near syncope, syncope or cardiac arrest, in- ducible during baseline electrophysiologic testing and not suppressed with oral antiarrhythmic agents, alone or in combination.

Preoperative evaluation and intraoperative mapping were performed as previously reported.” In brief, in- duction of VT was carried out by the introduction of single, double and triple extrastimuli at the right ven- tricular apex, right ventricular outflow tract or both, af- ter paced rhythms at 600, 400, and 400 to 600 ms.12 The same VT induction protocol was used while the pa- tients were receiving antiarrhythmic medications. He-

From the Electrophysiology Laboratory, Sinai Samaritan Medical Center, Milwaukee, Wisconsin 53233. Manuscript received May 3, 1988; revised manuscript received and accepted October 17, 1988.

Address for reprints: Jose Caceres, MD, Section of Cardiology, Cardiac Electrophysiology, Department of Medicine, East Carolina University School of Medicine, Greenville, North Carolina 27858- 4354.

296 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 63

modynamic evaluation consisted of coronary angiogra- phy and radionuclide ventriculography at rest. Endocar- dial mapping of the induced VTs was done by applying bipolar roving electrodes along the perimeter of the visi- ble scar in a sequential clockwise fashion during normo- thermic cardiopulmonary bypass, Site of VT origin was defined as the earliest endocardial site of activation identified by the local electrogram in the latter half of diastole before onset of the surface QRS complex.13

Surgical procedures: All patients underwent cryo- surgery as the primary ablative technique. Endocardial cryoablation was performed by means of a curved probe with a 15mm diameter circular flat freezing tip applied to each desired site for 2 minutes, at -60°C during cold cardioplegic arrest. The infarcted scar was encir- cled with cryolesions in 4 patients in whom no VT could be induced intraoperatively.5 In addition to cryosurgery, 11 patients had subendocardial resection of the well-de- marcated anteroseptal scar. All operative survivors were monitored continuously. They underwent electrophysio- logic studies 10 to 15 days after cryosurgery and were subjected to the complete stimulation protocol previous- ly described. In the event of inducible VT, serial drug electrophysiologic testing was again carried out. Radio- nuclide ventriculogram was also obtained before hospi- tal discharge to compare left ventricular ejection frac- tions with those measured before surgery. Patients were followed as previously described.’ i The terms of sus- tained monomorphic VT, surgical success, clinical suc- cess and clinical failure used in this study also have been previously defined. l l

Statistical analysis: Descriptive variables are report- ed as mean f standard deviation. Statistical analysis was performed by the Student t test and Pearson prod- uct-moment correlation. A p value <0.05 was consid- ered to be significant.

RESULTS Preoperative data: The clinical characteristics of

the 39 patients are listed in Table I. Prior myocardial infarction occurred 1 to 276 months (mean 85 f 84) before cryosurgery. Six patients (15%) had myocardial infarction within 2 months of surgery. Twenty-one patients were in New York Heart Association function- al class I, 15 in class II and the remaining 3 in class III.

There were 48 discrete sustained monomorphic VTs induced during preoperative electrophysiologic studies in the 39 patients. Thirty-one patients had a single tachycardia configuration and 8 had 12 configurations. A right bundle branch block configuration was present in 30 (62%) of the 48 VTs, whereas the remaining ones (38%) had a left bundle branch block configuration. The mean VT cycle length was 282 f 64 ms.

Operative data: Intraoperative endocardial mapping was accomplished in 35 of the 39 patients (90%). A total of 67 distinct VTs were induced intraoperatively. Eight patients had a single morphology, whereas the re- maining 27 had multiple VT configurations. The mean VT cycle length was 274 f 52 ms. Right and left bun-

TABLE I Clinical Characteristics of 39 Patients with Ventricular Tachycardia

Age (yrs) Men/women MI location

61 f9 34/5

Anterior (%) Inferior (%) Both (%)

Coronary arteries with >50% diameter stenosis LV aneurysm (%) Clinical presentation

Cardiac arrest (%) Syncope (%) Near syncope (%) Angina pectoris (%)

Heart failure (%) LV ejection fraction (%)

Preoperative Postoperative

Drugs trials/patient No. VT/patient

Preoperative EPS (n = 39) Operative mapping (n = 35)

16 (41) 22 (56)

1 (3) 2 f 0.8

29 (76)

18 (46) 11 (28)

8 (21) 2 (5)

21 (55)

33* 13 39s 11

3.8zk 1.4

1.2f0.4 1.9f0.6

EPS = electrophysiologic study; LV = lef? ventricle; MI = myocardlal Infarction; VT = ventricular tachycardia. sustained and monomorphic.

Cryosurgery + SER (%) Cryolesions/heart Coronary bypass grafting (%) LV aneurysm repair (%) Aortic valve replacemen

dle branch block configurations were observed in 55 and 45% of these tachycardias, respectively. Sites of earliest VT endocardial activation during tachycardia included 38 (57%) in the septum, 15 (22%) between the ventricu- lotomy and the mitral valve anulus (anular isthmus), 8 (12%) in the lateral wall, 5 (7%) at the base of the pos- terior papillary muscle and the remaining 1 at the ante- rior papillary muscle. In each of the 4 patients in whom VT was not inducible after left ventriculotomy, a VT of single configuration had been initiated preoperatively. Thus, a total of 71 distinct VTs were amenable to surgi- cal ablation.

The surgical procedures are listed in Table II. The mean number of cryolesions per heart was 11 f 3 (6 to 1 S/heart) in anterior infarctions and 10 f 3 (6 to 16/ heart) in inferior infarctions. This difference was not statistically significant (p = 0.2). Eleven patients had subendocardial resection of their well-demarcated large anteroseptal scars before cryosurgery was undertaken. Two sutureless myocardial leads (CPI, model K54) and 2 ventricular patch leads (CPI, models A67, L67 or both) for the automatic implantable cardioverter defi- brillator were placed in the 18 patients with clinical pre- sentation of cardiac arrest and in the 4 patients with evidence of unsuccessful mapping. However, the device

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SURGICAL ABLATION OF VENTRICULAR TACHYCARDIA

TABLE Ill Results and Follow-Up of 39 Patients with Ventricular Tachycardia I

Operative death (%) Postoperative death (“IO) Postoperative EPS (%) Surgical success (%) Clinical success (%) Clinical failure (“ID) Follow-up (mo) VT recurrence Death due to CHF Heart transplant Alive (February 1988) NYHA functional class I (%) NYHAfunctional class II (%)

1 (2.5) 1 (2.5)

37 (95) 28 (76)

6 (16) 3 (8)

18f12 0

36 21 (60) 14 (40)

CHF = congestive heart failure; EPS = electrophysiologic study; NYHA = New York Heart Association; VT = ventricular tachycardia, sustained and monomorphic.

was subsequently implanted only in 3 patients who were clinical failures. Complete heart block in 1 patient was the only nonfatal complication of cryosurgery.

Postoperative results: A 72-year-old woman with refractory congestive heart failure and incessant VT for which cryoablation was an emergency intervention, died of pump failure 2 days after surgery. On autopsy, no aneurysm formation or rupture at the 8 sites of freezing was found. The only postoperative death occurred 56 days after surgery as a result of sepsis and renal failure, with no recurrence of VT. Therefore, 37 patients (95%) underwent postoperative electrophysiologic evaluation (Table III).

Surgical success was achieved in 28 patients (76%). Of the remaining 9 patients, 1 had spontaneous uniform VT on the fifth postoperative day and 8 had inducible VT during electrophysiologic testing. In each of these patients, a single VT configuration was initiated and, although the rate was usually slower, the morphology was similar to previously induced VTs in all but 1. In this last patient, cryosurgery ablated his 2 preoperative induced tachycardias, but a previously unobserved VT was induced with triple extrastimuli. Consequently, 63 of the 71 (89%) induced tachycardias before surgery were successfully ablated. Oral antiarrhythmic drugs suppressed inducible VT in 6 patients. Thus, clinical success was achieved in an additional 16%. The remain- ing 3 patients failed antiarrhythmic drug trials and had automatic cardioverter defibrillators implanted before their hospital discharge. The clinical failure rate there- fore was 8%.

Of the 5 patients who underwent cryoablation at the bases of their posterior papillary muscles, 1 died 56 days after surgery as mentioned. Cryosurgery successfully ablated the tachycardias in the remaining 4 patients. Postoperatively, none of them developed significant mi- tral regurgitation.

The addition of subendocardial resection was at the discretion of the surgeon. It was performed whenever there was an easily resectable and well-demarcated an- teroseptal scar. Interestingly, surgical success was achieved in 8 of the 11 patients (73%) who had suben-

docardial resection as well as cryosurgery. Thus, in our study, no significant difference in surgical outcome was found between patients who had cryosurgery alone (78%) and those who had subendocardial resection to- gether with cryothermic ablation.

Analysis of surgical results by location of myocardial infarction showed a striking similarity. In patients with VT related to anterior wall infarction, the surgical and clinical successes were 75 and 17%, respectively, where- as in patients with inferior wall infarction these were 77 and 16%, respectively.

Comparing patients who had successful versus un- successful surgical results, no significant difference was found regarding clinical presentation, severity of coro- nary artery disease, myocardial infarction location, left ventricular ejection fraction, VT characteristics before or during mapping, or NYHA functional class.

Left ventricular ejection fraction remained well pre- served after surgery in 38 (97%) of the 39 patients in whom a resting radionuclide ventriculography was ob- tained postoperatively. There was no correlation be- tween myocardial infarction location or number of cryo- lesions and postoperative changes in ejection fraction (r = -0.025). Overall, mean left ventricular ejection be- fore and after surgery was 33 f 13 and 39 f 1 l%, respectively (p <O.Ol) (Table I).

Follow-up: Long-term follow-up periods ranged from 2 to 36 months (mean 18 f 12) (Table III). One patient with severe heart failure died 5 months after surgery due to low cardiac output without recurrence of VT. A 41-year-old patient with severe heart failure un- derwent heart transplant 7 months after successful cryo- surgery without recurrence of ventricular tachycardia. In the remaining patients, no spontaneous recurrence of VT has been documented and no episode of cardiac ar- rest, syncope or defibrillator discharge has occurred. No significant mitral regurgitation has developed in the 4 survivors who had cryosurgery at the base of the papil- lary muscle. The 6 patients who required antiarrhyth- mic drugs postoperatively for inducible VT continued to receive these agents. The 3 patients who received auto- matic cardioverter defibrillators have not received any antiarrhythmic medications since surgery. Of the 35 liv- ing patients, excluding the 1 who had heart transplant, 21 (60%) were in New York Heart Association func- tional class I and the remaining 14 (40%) patients were in functional class II. Of the 3 patients who were in preoperative functional class III, 1 was an operative death, another died 5 months after surgery as men- tioned and the remaining patient underwent heart trans- plantation.

DISCUSSION Success of cryoablation: Encircling endocardial

cryoablation for VT due to coronary artery disease was described by Guiraudon et al5 in 1983. Since then, cryo- surgery has been used in patients with medically refrac- tory VT as the sole technique or, more often, in combi- nation with other techniques such as subendocardial re-

298 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 63

section.2s14m17 However, the surgical efficacy and long-term results of cryosurgery for drug-resistant VT have not been confirmed by subsequent reports and re- main to be established.

In the present study, cryosurgery resulted in a high surgical cure rate of 76%, as assessed by programmed ventricular stimulation. The cryotechnique successfully abolished 89% of the morphologically distinct inducible VTs. In addition, 16% responded to antiarrhythmic drugs that had previously failed to control their tachy- cardias. Therefore, surgery by itself or in combination with antiarrhythmic agents was successful in 92% of pa- tients (Table III). Because our population is not differ- ent from that of similar studies that used other surgical approaches, such as subendocardial resection, these re- sults compare quite favorably with those previous re- ports7Al8,19 and indicate that cryosurgery is highly ef- fective for ablation of VT due to coronary artery dis- ease.

Multiple sites of VT origin and absence of left ven- tricular aneurysm have been reported to predict the re- currence of sustained VT after subendocardial resec- tion.8 However, the recurrence of VT in our 9 patients after surgery apparently was not related to the clinical, hemodynamic, angiographic or electrophysiologic vari- ables nor to the sites of earliest activations.

The operative survivors had a high long-term success rate (100%) regarding control of recurrent sustained VT. Indeed, late mortality was not due to VT recur- rence but was caused by heart failure, which probably reflected poor preoperative left ventricular performance rather than adverse effect of the cryotechnique. No sig- nificant mitral regurgitation developed in the 4 survi- vors who had cryoablation at the base of the posterior papillary muscle nor in any other patient. Thus, cryo- surgery yielded excellent long-term results in these pa- tients.

Lefl ventricular performance: Cryoablation did not result in deterioration of left ventricular ejection frac- tion The overall mean ejection fraction even improved (33 to 39%) before and after surgery. Guiraudon et allo also reported a significant improvement in left ventricu- lar ejection fraction after cryoablation. In our patient population, left ventricular function remained well pre- served despite the number of cryolesions per heart (Ta- ble 11). Thus, the judicious use of cryolesions to ablate VT does not appear to have a detrimental effect on left ventricular ejection fraction. This preservation of left ventricular function may be related to the application of cryolesions on the border zone of the myocardial scar without disruption of the surrounding viable myocardi- um.2o Because typical lesions produced by cryosurgery at -6O’C for 2 minutes are 3 to 6 mm deep, the dam- aged tissue is also relatively small compared with the total left ventricular mass. The extent of damage to functional normal myocardium is therefore limited.

Benefits and limitations: Cryosurgery for ablation of sustained monomorphic VT due to coronary artery dis- ease seems to offer the following advantages: (1) abla-

tion of the arrhythmogenic area, with a resultant elec- trically silent lesion that preserves the structural integri- ty of the myocardium iO,rQo; (2) the healed cryolesion does not seem to be arrhythmogenic because the scar produced by cryothermia is homogeneous, firm and well-dema&ated.10~20 Cryothermia is ideal in the abla- tion of arrhythmogenic sites not amenable to subendo- cardial resection such as the papillary muscles, valvular areas and poorly circumscribed scars. In addition, it avoids papillary muscle resection and mitral valve re- placement in tachycardias arising from this structure’ l; (3) cryosurgery preserves the strength of left ventricular aneurysm margins by avoiding scar tissue excision, ren- dering ventriculotomy repair less difficult; (4) it may be safely applied to friable border zones in patients with recent myocardial infarction; and (5) cryoablation is simple to use, relatively safe and well tolerated.‘O

On the other hand, cryosurgery seems to have the following limitations: (1) it can increase the duration of operation, as well as cardiopulmonary bypass and aortic cross-clamp times, especially when a large mass of myo- cardium needs to be ablatedlO; (2) although the depth of cryolesions depends upon the duration and degree of freezing, depth is difficult to evaluate with the current technique; (3) lack of induction of ventricular tachycar- dia immediately after cryosurgery is not reliable in es- tablishing successful ablationlO; (4) epicardial cryotech- nique near the coronary arteries may lead to thrombosis and progressive occlusive lesions10,20; and (5) complete atrioventricular block may occur, as was seen in 1 pa- tient who underwent cryothermia of the upper septum. This nonfatal complication has been previously reported in a patient who had cryolesions applied to the septal area with a biventricular approach.21

Acknowledgment: We are grateful to Brian Miller and Carol Gilbert for their assistance in the preparation of this manuscript.

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