988

Ventricular Fibrillation and Polymorphic VentricularTachycardia with Critical Coronary Artery Stenosis:

Does Bypass Surgery Suffice?

ANDREA NATALE, M.D., JASBIR SRA, M.D., KATHI AXTELL, R.N.,CHERYL MAGLIO, R.N., ANWER DHALA, M.D., ZALMEN BLANCK, M.D.,

SANJAY DESHPANDE, M.D., MOHAMMAD JAZAYERI, M.D.,and MASOOD AKHTAR, M.D.

From the Electrophysiology Laboratory. Milwaukee Heart Institute of Sinai Samaritan Medical Center,and St. Luke's Hospital, University of Wisconsin-Milwaukee Clinical Campus, Milwaukee, Wisconsin

ICD Therapy and CABG for Sudden Death, introduction: Previous studies have sug-gested that coronary artery bypass surgery is sufficient to prevent recurrence of sudden deathin patients with critical coronary artery stenosis presenting with ventricular Hhrillation orpolymorphic ventricular tachycardia. We present our experience in patients with one or moreepisodes of sudden death associated with documented ventricular fibrillation or polymorphicventricular tachycardia and severe operable coronary artery disease who underwent defibrilla-tor implant at tbe time of bypass surgery.

Methods and Results: Fifty-eigbt consecutive patients (age 63 ± 8 years) were included in thisstudy. Eighteen of the 58 patients had no evidence of previous myocardial infarction. The meanejection fraction was 37 ± 13%. All patients underwent electrophysiologic study before and afterrevascularization. At tbe time of first defibrillator discharge, each patient was reevaluated t(texclude the presence of ischemia. The benefits of defibrillator imphint were estimated compar-ing the projected survival based upon defibrillator discbarge preceded by syncope or presyn-cope with survival curves generated including total deatb and sudden plus cardiac death. Aftera mean follow-up of 4.6 ± 2 years, 22 patients received appropriate shocks preceded by syncopeor presyncope, and an additional 19 patients received asymptomatic sbocks. At 4 years, survivalfree of total death was 71.2%, and the projected survival was 58.8% (P < 0.05). Multivariateanalysis showed that ejection fraction lower than 30% and induction of arrhythmia with one ortwo extrastimuli (S2, S3) were independent predictors for defibrillator discbarge. None of theremaining variables including age, gender, number of bypasses, history of myocardial infarc-tion, and type of arrbytbmias induced were predictive for deatb and occurrence of sbocks.

Conclusions: In patients witb ventricular fibrillation and polymorpbic ventricular tachycar-dia, bypass surgery does not protect from recurrence of life-tbreatening arrhytbmias, and, asin our population, defibrillator implant may have significant impact on survival. (J CardiovascElectrophysiol, Vol. 5, pp. 988-994. December 1994)

sudden death, revascularization, implantable defibrillator

Introduction has led to the belief that ischemia may be the trig-The high prevalence of significant coronary gering mechaiiism for fatal ventricular airhythmias

artery stenosis in sudden cardiac death survivoi^' '̂ "^ ^^f revasculanzation may represent an ade-quate therapeutic measure in this cohort. Althoughshort-lerm results frt>m the CASS Study and other

TAZL ~f '7' A . M . , »«r. ^̂ 1 II seHes^"^ seem to suggest a reduction, albeit mod-Address tor correspondence: Andrea Natale, M.D., Duke Univer- ^^.sityA'A Medical Cenler. 508 Fulton Slreet, Box 11 IA, Durham, ^St, of SUdden death after reVUSCUlarization, theNC 27705. Fax: 9 i 9-286-6861. role of coronary artery bypass surgery in the man-Manuscript received 21 September 1994; Accepted for publication agement of life-threatening ventricular arrhythmia30 November 1994. remains unsettled, particularly in patients pre-

Natale, et al. Therapy and CABG for Sudden Death 9R9

senting with ventricular fibrillation or polymorphicventricular tachycardia.

In this setting, the relative importance ofischemia and structural abnormalities, such as ven-tricular aneurysm and prior infarct, is difficult todistinguish. Implant of a cardioverter-defibrillatorin conjunction with coronary bypass surgery pro-vides an opportunity to assess if coronary reper-fusion alone or combination with a defibrillator isneeded to improve survival in this subset of patients.

We present our experience in consecutive patientswith critical coronary artery stenosis and suddendeath with documented ventricular fibrillation orpolymorphic ventricular tachycardia, who under-went coronary artery revascularization along withdefibrillator implant.

Methods

The study population included 58 consecutivesudden death survivors, 10 females and 48males, age 63 ± 8 years (range 44 to 83). Allpatients had one or more episodes of sudden deathassociated with documented ventricuiar fibrillationor polymorphic ventricular tachycardia along withsevere operable coronary artery disease. All patientswere assessed by thallium exercise scintigraphyand coronary angiography with biplane left ven-triculography using standard techniques. No patienthad evidence of acute myocardial infarction at thetime of cardiac arrest. However, 40 patients hadprevious history of myocardial infarction.

Diagnostic Work-Up and Therapeutic Interventions

All patients underwent pre- and postoperativeelectrophysiology study after discontinuation ofany antiarrhythmic drug therapy. Briefly, the stim-ulation protocol used in our laboratory includespacing with two basic drive cycle lengths at 400and 600 msec and extrastimulus testing with up tothree extrastimuli. In addition, a short-long pacingsequence with up to two extrastimuli was deliv-ered.** Programmed electrical stimulation was per-formed from the right ventricular apex and rightventricular outflow tract both in a drug-free stateand during isoproterenoi infusion. In the presenceof severe coronary artery disease, isoproterenoiinfusion rate was titrated to achieve 20% increaseof the heart rate. Care was taken to avoid precip-itation of ischemia during the test. In patients withinducible sustained monomorphic ventricular tachy-cardia, the effect of intravenous infusion of pro-cainamide (15 mg/kg) was tested. Coronary artery

bypass grafting was carried out using moderatedhypothermia and crystalloid cardioplegia. Both arte-rial and venous grafts were placed to all majorvessels with stenosis greater than 50% by angio-graphic method. After temiination of cardiopul-monary bypass, the defibrillation electrtxle .systemusing two epicardial patches and two screw-in leadswas placed in 56 pafients. Two patients underwenttransvenous defibrillator implant 7 days after revas-cularization.

Follow-Up Testing

Following coronary bypass surgery and beforedischarge, all patients were subjected to repeat elec-trophysiologic testing using the same protocoldescribed above. Cardioverter-defibrillator func-fion was reevaluated before discharge, at 1 month,and at regular intervals of 3 months. To avoiddefibrillator discharge for self-limited ventriculararrhythmias, devices were programmed with longdetection fimes (>: 20 beats for Medtronic [Min-neapolis, MN. USA] devices) when possible. Atthe time of the first defibrillator discharge, eachpatient was reevaluated with coronary angiogra-phy, thallium exercise treadmill study, or both.

Statistical Analysis

Continuous data was presented as mean ± SD.Patient survival was calculated by use of theKaplan-Meier method and presented as the per-centage surviving. The standard errors for survivalat 2, 3, and 4 years for total deaths or suddenplus cardiac deaths were used to determine thesignificance of survival in these two outcomes fromthe projected survival. The Cox proportional haz-ards model was utilized to determine what fac-tors were independent predictors for defibrillatordischarge and death. A two-tailed P < 0.05 wasconsidered significant. The data was analyzed usingthe SAS System (SAS Institute, Cary, NC, USA).

Results

Of the 58 patients, none had evidence of a dis-crete aneurysmal segment. All patients had evi-dence of significant reversible ischemia at the pre-operative thallium exercise imaging. Eighteen ofthe 58 pafients had no wall-motion abnonnalitieson left ventriculography. The mean ejection frac-tion was 37 ± 13%. Triple vessel disease was pres-ent in 24 patients, double vessel disease in 27patients, and single vessel disease in the remain-

990 Journal of Cardiovascular Electrophysiology Vol. 5. No. 12, December 1994

ing 7 patients. The number of bypass grafts rangedfrom 1 to 6. with an average of 3.1 grafts perpatient. The intraoperative mean defibrillationthreshold was 8.9 ± 3.8 joules.

Programmed Stimulation Response

Information relative to the outcome of the pre-and postoperative electrophysiologic study is shownin Table 1. The preoperative programmed electri-cal stimulation showed inducible ventricular fibril-lation in 12 patients, inducible sustained monomor-phic ventricular tachycardia in 33 patients,nonsustained monomorphic or polymorphic ven-tricular tachycardia in 8 patients, and no induciblearrhythmia in 5 patients. Only the latter 5patients were tested on isoproterenoi and remainednoninducible. None of the patients with induciblemonomorphic ventricular tachycardia became non-inducible after procainamide infusion. Seven to 10days after surgery, the repeat electrophysiologicstudy showed inducible ventricular fibrillation in8 pafients, inducible sustained monomorphic ven-tricular tachycardia in 32 patients, nonsustainedmonomorphic or polymorphic ventricular tachy-cardia in 10 patients, and noninducible arrhythmiasin 8 patients. Three patients who had inducibleventricular fibrillation before revascularization hadno inducible arrhythmia after surgery, and twopatients with inducible sustained monomorphicventricular tachycardia at the preoperative elec-trophysiologic testing showed nonsustainedmonomorphic ventricular tachycardia after bypasssurgery. In addition, one patient with inducible ven-tricular fibrillation before surgery was found tohave inducible monomorphic ventricular tachy-cardia after revascularization. After surgery, 12patients required testing during isoproterenoi infu-

TABLE 1Outcome of the Pre- and Postrevascularization

Electrophysiologic Study

No Indue VF SMVT NSVTPre-op

Post-op

Prc-op = before surgery: Po.st-op = after surgery; Noindue = patients with noninducible arrhythmias; SMVT =patients with inducibie sustained monomorphic ventriculartachycardia; NSVT = patients with inducible nonsustainedmonomorphic and polymorphic ventricular tachycardia;VF = patients with indutible ventricular fibrillation.

TABLE 2Occurrence of Shocks Relative to the Re.sults of the

Electrophysiologic Sludy After Surgery

No Indtu- SMVT VF NSVTNo shockAppr shockAsymp shock 13

No Indue - patients with noninducible arrhythmias;SMVT = patients with inducible sustained monomorphicventricular tachycardia; NSVT = patient.s with induciblenonsustained monomorphic and polymorphic venlriculartachycardia; VF = patients with inducible ventricularfibrillation; Appr shock = number of patients receivingappropriate shocks; Asymp shock = number of patientswith asymptomatic shocks.

sion being noninducible in the drug-free state.No tachyarrhythmias could be induced in 8,whereas nonsustained ventricular tachycardia wasobserved in the remaining patients. Twenty-fivepatients had inducible arrhythmia using one or twoextrastimuli, whereas 28 patients required threeextrastimuli.

Outcome at FoUow-Up

After a mean follow-up of 4.6 ± 2 years, 17patients did not receive any shocks, whereas 22patients received appropriate shocks defined asthose preceded by syncope or presyncope or asso-ciated with documented ventricular fibrillation.Appropriate shocks were observed in 13 patientswith inducible sustained monomorphic ventriculartachycardia at postoperative eiectrophysiologic test-ing, in 3 with no inducible arrhythmias, in 2 withinducible ventricular fibrillation, and in 4 withinducible nonsustained monomorphic or polymor-phic ventricular tachycardia. In addition, 19 patientsreceived asymptomatic shocks. The overall rela-tionship between the results of the postoperafiveelectrophysiologic testing and occurrence of shocksis shown in Table 2. Among the patients whoreceived shocks, evidence of ischemia at the timeof the first defibrillator discharge was observedonly in 3 patients. In 2 of these 3 patients, shockdelivery was associated with occurrence of ven-tricular fibrillation, whereas sustained monomor-phic ventricular tachycardia was documented inthe remaining patient. One of these patients hadmultiple shocks, which turned out to be related toventricular fibrillation occurring mostly during exer-cise as documented by 24-hour Holter monitor-ing {Fig. 1). After repeat angiographic study, twoof these patients underwent successful balloonangioplasty followed by no fijrther delibrillator dis-

Natale, et al. Therapy and CABG for Sudden Death 991

charges, whereas the remaining patient was notconsidered a suitable candidate for either balloondilatation or repeat bypass surgery and was, there-fore, treated medically. The latter patient contin-ued to experience periodic ventricular arrhythmiaswith defibrillator discharge despite maximalpharmacologic therapy.

Survival Analysis and Predictors of DefibrillatorDischarge

Actual survival at 2, 3, and 4 years was 81.6%,76.6% and 71.2%, respectively, whereas the pro-jected survival, based upon defibrillator dischargepreceded by syncope, presyncope, or docu-

mented ventricular fibrillation, was 72.7%, 64.7%,and 58.8% respectively. The cause of death wassudden in 2 patients and related to end-stage heartfailure in 4 patients. Nine patients died from non-cardiac reasons, including a car acxident in 1 patient,cancer in 4, cardiovascular accident in 2, and end-stage renal insufficiency in 2. Projected survivalresults were significantly lower than actual sur-vival at 3- and 4-year (P < 0.05) follow-up. Analy-sis including even the asymptomatic shocks in theprojected survival showed a significant benefit ascompared to total death starting at 1-year follow-up (55.8% vs 91.2%, P < 0.01). This level ofsignificance persisted at 2 (49.2% vs 81.6%), 3(38.1 % vs 76.6%), and 4 years (28.4% vs 71.2%).

Figure I. Selected tracing from Hotter recording of a patient who e.xperienced multiple asymptomatic shocks, mo.stly duringexercise 2 years after surgery. This patient had no inducibie arrhythmias both at the etectrophysiologic testing pre- andpostrevascularization. Upper tracing shows nonsustained potymorphic ventricutar tachycardia. In the middte and bottomtracings, identification and termination of ventricular fibrillation by the defibrillator were documented. In this patient, criticalstenosis in one of the venous grafts was successfulty treated with angioplasty, which resulted in abotition of defibrlttator dis-charge.

992 Journal of Cardiovascular Electrophysiology Vol. 5, No. 12. December 1994

When the sudden death and the cardiac death free-survival was compared with the projected survival,a significant difference was observed starting at 2-year (P < 0.05) follow-up (Fig. 2). Multivariateanalysis showed that none of the variables exam-ined, including age, gender, number of bypasses(< 2), arrhythmia inducibility, type of arrhythmiasinduced, and history of previous myocardiai infarc-tion, were predictive for death and occurrence ofshocks. However, ejection fraction lower than 30%(P = 0.0002) and induction of arrhythmias withone or two extrastimuli versus three extrastimuli(P = 0.02) were found independent predictors fordefibrillator discharge (Table 3).

Discussion

Most victims of sudden cardiac death haveadvanced chronic atherosclerotic lesions.' More-over, direct evidence that transient myocardiaiischemia may precipitate fatal ventricular arrhyth-mias is available.^*' In view of the above, thepossible role of acute coronary event as a cause ofsudden death has been postulated, and coronaryrevascularization alone has been advocated as asufficient modulating factor of the arrhythmogenicsubstrate.

1.0rt

> 0.8

OC

0) 0.6

<

go

0.4

0.2

However, since evidence of reversible ischemiawas found only in three patients at the time ofthe first appropriate defibrillator discharge, ourfindings argue against overt ischemia as the pre-dominant lethal triggering mechanism of suddendeath. In this respect, the extrapolated projectedsurvival, assuming that if defibrillator interventionpreceded by syncope or presyncope had nottaken place then arrhythmic death would haveensued, was significantly lower thiin actual totalmortality starting 3 years after bypass surgery.

This improvement in survival was maintaineddespite the presence of high overall noncardiacmortality. In addition, a much earlier and con-spicuous benefit would have resulted by includingin the analysis defibrillator interventions notassociated with symptoms. It could be argued thatin the first-generation devices, such as most ofthose used in this study, the definition of appro-priate shock may be inaccurate because of theunavailability of stored electrograms. However,recent studies'"^ have shown that the definition usedfor appropriate shock in our study underestimatesrather than overestimates the incidence of appro-priate shocks. Certainly, it cannot be fully excludedthat some of the episodes of ventricular tachy-arrhythmia might have been self-terminating and.

SCD & CD

. PS vs. TD NS < 0.05 < 0.05PS vs. SCD & CD < 0.05 < 0.01 < 0.01

12 24MONTHS

36 48

Figure 2. Kaplan-Meier survival curves generated for total mortality survival (TD), sudden death and cardiac death survival(SCD and CD), and projected survival (PS). At 4 years, survival free of total death was 71.2%. whereas survival free of sud-den and cardiac death was 86.3%, and projected sur\-ival was 58.8%. The latter was obtained a.ssuming that the first appro-priate defibrillator discharge would have been fatal. At the bottom, P values at 24, 36, and 48 months are shown.

Natale, et al Therapy and CABG for Sudden Death 993

TABLE 3Clinical Predictors of tmplantableCardiovertcr-Defibrillalor Shocks

AgeSexEF<30ST-SI inductionNo. of bypasses (^ 2)Arrhythmia inducibilityType of arrhythmia inducedMI

P Value

0.30.70.00020.020.20.40.60.1

Odd.s——.4.33.0————

EF < 30 = ejection fraction < 30%; S^-Sj induction =inducible arrhythmias using one or two extrastimuli; Typeof arrhythmia induced = predictive value of the type ofarrhythmia induced at the postoperative electrophysiologicstudy; Arrhythmia inducibility = predictive value of in-ducibility of some type of arrhythmias at the electro-physiologic study postrevascularization; Ml = predictivevalue of previous myocardiai infarction.

therefore, not lead to death. However, the use oflong detection intervals as in our population shouldhave limited this p)ossibility. It is also conceivable,although not likely., that supraventricular tachy-cardias with rapid ventricular response could haveresulted in detibrillator discharge preceded by symp-toms suggestive of imminent cardiovascular col-lapse. However, placement of the defibrillatingelectrodes on the ventricular myocardium is unlikelyto terminate atrial arrhythmias that would be, there-fore, associated with the occurrence of multipleconsecutive shocks.

On the other hand, it must be noted that, asproved in two of our patients, graft occlusion ordisease progression in the native vessels can beunveiled by recurrent ventricular fibrillation. Sinceprogressive saphenous grafts and native coronaryartery atherosclerosis are more likely to occur 5 to10 years after revascularization,' it is conceivablethat such events may become even more pre-dominant with longer follow-up. In this respect,the inability to predict time and modality ofischemia recurrence more strongly support the needfor a more aggressive preventive approach such asused in our series.

Postoperative electrophysioiogic testing has beenproposed as a useful means to predict a favorableoutcome after revascularization.'"'^ Nevertheless,in our series, while this was true for patients withinducible arrhythmias, a considerable number ofindividuals with no inducible arrhythmia also hadappropriate shocks (Table 2). Even though such ascenario often suggests a dynamic trigger, suchas acute ischemia, no overt evidence for such anoccurrence was found in most of these cases. In

this respect, it is conceivable that with a longerfoUow-up, more patients with no inducible ven-tricular tachycardia/ventricular fibrillation mayappropriately use the device. It is also likely thatthe predictive accuracy of electrophysiologic test-ing will decrease in a substantial proportion ofpatients 5 to 10 years after surgery as the substratechanges take place, recreating the same conditionthat initially produced sudden death. It is tempt-ing to postulate that individuals initially present-ing with sudden cardiac death as the manifestationof coronary disease may have a similar presenta-tion in the event that ischemia recurs. Since recur-rent ischemia can result from a variety of reasons,i.e., inadequate revascularization. progression ofnative vessel disease, and graft occlusion, the useof additional modes of arrhythmia control suchas defibrillator therapy may be appropriate, at leastin patients with p<.x:)r left ventricular function.

In conclusion, even though critical coronarystenosis is found in patients resuscitated from ven-tricular fibrillation or polymorphic ventriculartachycardia, ischemia may not be the predomi-nant contributing factor. Instead, a deranged elec-trophysiologic substrate appears a more likelyexplanation. However, in the event ischemia isthe cause, it could recur unpredictably after revas-cularization, and, therefore, concomitant defibril-lator therapy should be considered to alter theotherwise dismal prognosis of this subgroup ofpatients. Finally, although several criticisms canbe raised regarding the design of our study, theresults should at least alert physicians to be sus-picious and open-minded when considering ther-apeutic strategies for patients such as thoseincluded in this series.

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994 Journal of Cardiovascular Electrophysiology Vol. 5, No. 12. December 1994

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