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Ann Thorac Surg 2002;74:1510-1516
© 2002 The Society of Thoracic Surgeons

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Original article: cardiovascular

Surgical coronary revascularization and antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest

^a Cardiac Surgery, Harvard Medical School, Boston, Massachusetts, USA
^b Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Accepted for publication July 8, 2002.

* Address reprint requests to Dr Torchiana, Division of Cardiac Surgery, Massachusetts General Hospital, Bullfinch 119, 55 Fruit St, Boston, MA 02114, USA
e-mail: dtorchiana{at}partners.org

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
BACKGROUND: Patients who survive out-of-hospital cardiac arrest are at high risk for recurrent arrest. Coronary artery bypass grafting (CABG) confers a survival advantage, but it is unclear whether antiarrhythmic drugs or an implanted defibrillator confer added benefit. This study was designed to determine predictors for further treatment, survival, and therapeutic internal cardiac defibrillator (ICD) discharge in this patient population.

METHODS: One hundred and eight patients undergoing CABG after out-of-hospital cardiac arrest were identified over a 12-year period. Case records were retrospectively reviewed. Follow-up was obtained and predictors of outcome events were analyzed.

RESULTS: Fifty-four (50%) patients underwent CABG only. Fifty-four received additional treatment that included ICD placement in 23 (21%), antiarrhythmic medications in 19 (18%), or both in 12 (11%). Predictors of ICD placement included left ventricular ejection fraction (LVEF) less than 40% and perioperative intraaortic balloon counterpulsation. ICD or medical management increased survival in patients with LVEF <40%. Predictors of increased mortality included age >65 years, Cleveland Severity Score >8, and female gender. Predictors of therapeutic ICD discharge included age >65 years, reoperative CABG, LVEF <40%, and positive postoperative electrophysiological (EP) study. No patient with a negative postoperative EP study received an ICD, and none suffered sudden cardiac death during follow-up.

CONCLUSIONS: Patients with coronary artery disease anatomically suitable for CABG who survive an acute out-of-hospital cardiac arrest should undergo EP testing after CABG. Approximately half of these patients are adequately treated by CABG alone. The remainder may benefit from ICD placement or medical antiarrhythmic management.

	Introduction

Top Abstract Introduction Material and methods Results Comment References

 
Approximately 300,000 cases of sudden cardiac death are reported each year in the United States [1], accounting for almost 50% of all deaths due to cardiovascular disease [2]. The majority of sudden cardiac deaths occur as a result of refractory ventricular arrhythmia [3]. Approximately 15% of patients who survive sudden cardiac death will suffer recurrent cardiac death within the next 12 months. This risk decreases by 5% to 7% per annum in subsequent years. Diffuse coronary atherosclerosis is the most common finding on postmortem examination [4]. Multiple studies have demonstrated that surgical revascularization suppresses ventricular arrhythmias and improves long-term survival [5–9] in patients with sudden cardiac death. However, the criteria for use of electrophysiological (EP) studies and additional therapy, in the form of internal cardioversion devices (ICD) or medical antiarrhythmic therapy, are vague. Furthermore, the influence of these therapies on survival is unclear. The goals of this retrospective study were to determine the appropriate use of EP studies in this population; to determine predictors of need for ICD placement; to determine predictors of survival after ICD placement or medical management; and to determine predictors of therapeutic ICD discharge in patients surviving sudden cardiac death and undergoing coronary artery bypass grafting (CABG).

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

 
One hundred and fourteen patients undergoing CABG after surviving an acute out-of-hospital cardiac arrest were identified over a 12-year period at our hospital. Five patients undergoing ventricular endoaneurysmorrhaphy and 1 patient undergoing mitral valve replacement with CABG were excluded from the study. The remaining 108 patients undergoing only CABG constitute the basis for this report.

After approval by the Institutional Review Board, records were retrospectively reviewed. Follow-up was established by written letter or telephone contact with the patient, physician, or family member, as appropriate. Follow-up was 99% complete at 7 years. Total follow-up was 526 patient-years.

All defibrillator discharges were evaluated. If the triggering arrhythmia could not be determined by device interrogation, discharges were classified as appropriate if the discharge occurred during sleep, or was associated with symptoms. Discharges were deemed inappropriate if their delivery was associated with a rhythm or cause other than a ventricular arrhythmia, such as a sensing lead malfunction.

Deaths were classified according to probable cause. Sudden cardiac death was defined as death occurring within 1 hour of the development of cardiac symptoms in a previously stable patient. Non–sudden cardiac death was defined as death due to cardiac disease with preceding symptoms of more than 1 hour’s duration.

Statistical analysis was performed using BMDP Statistical Software (version 7.1). Differences between groups were analyzed using Fischer’s exact test and the ² test where appropriate. Kaplan-Meier survival curves were analyzed using the log-rank test, and independently predictive risk factors were identified using stepwise logistic regression analysis. A p value of <0.05 was considered statistically significant.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
Over a 12-year period, 108 patients underwent CABG after prehospital cardiac arrest. There were no significant differences in age or gender between the patients undergoing only CABG, CABG plus ICD placement, CABG plus medical antiarrhythmic therapy alone, or CABG plus ICD plus medical antiarrhythmic therapy (Table 1). Ten (9.3%) patients had undergone remote CABG. Five (4.6%) patients had undergone remote percutaneous transluminal coronary angioplasty (PTCA). Half the patients had sustained prior remote myocardial infarction (MI). Thirty-four patients had a history of one prior MI. Fourteen patients had two prior MIs, and 6 patients had three or more prior MIs. All prior remote events were evenly distributed between all four groups (Table 1).

All patients underwent CABG. Ten patients underwent redo CABG. An average of 3.5 ± 1.2 bypass grafts were performed in each patient (range, one to seven). The extent of revascularization was similar between all patients undergoing CABG only, CABG plus ICD, CABG plus medical antiarrhythmic therapy, and CABG plus ICD plus medical antiarrhythmic therapy (Table 1). The median number of days between presentation and operation was 18 ± 35 (range, 3 to 190 days). This duration was similar between the four groups (Table 1).

Signal-averaged electrocardiograms were not used. EP studies were performed pre- or postoperatively at the discretion of the attending physicians. Patients were considered inducible if the stimulation protocol resulted in induction of a sustained ventricular arrhythmia lasting more than 30 seconds, or causing hemodynamic deterioration requiring intervention. Discharge from the hospital on class I or class III antiarrhythmic medication constituted medical antiarrhythmic therapy. Treatment with ß-blockers or digoxin was not considered supplemental arrhythmia therapy.

Fifty-four (50%) patients underwent preoperative EP studies, and of these, 38 (70%) patients were inducible (Fig 1A). The percentage of patients undergoing preoperative EP studies and the percent inducible was evenly divided among the four groups (Table 1). Twenty-five of 38 patients inducible at preoperative EP study (66%) underwent postoperative EP study. Of these, 16 (64%) remained inducible. Thirteen (81%) of these received medical therapy with or without ICD placement. Forty-one patients underwent postoperative EP study only (Fig 1B). Twenty-two (54%) patients were noninducible, and 91% of these patients underwent CABG only. Nineteen (46%) patients were inducible, and 90% of these patients required ICD placement or medical therapy in addition to CABG. Patients requiring ICD placement were more likely to suffer from ventricular dysfunction with left ventricular ejection fraction (LVEF) < 40% (p = 0.001), and to have required perioperative intraaortic balloon counterpulsation (p = 0.002).

View larger version (26K): [in this window] [in a new window]   Fig 1. Use of electrophysiological (EP) study to determine need for additional therapy (internal cardioversion device [ICD] or medical antiarrythmics) in this cohort. (A) With preoperative EP study. *One patient died of sudden death and refused ICD. **One patient died of sudden death and refused ICD; seen in first year of experience. ¶Two patients died of sudden death and received only medical therapy; 1 was seen in first year of experience. (B) No preoperative EP study. One patient died of sudden death; seen in first year of experience. One patient died of sudden death, received only medical therapy, and refused ICD; seen in first year of experience. (CABG= coronary artery bypass grafting;meds = medications; mgmt = management; pt = patient.)

After operation, a total of 13 patients (12%) required prolonged ventilation. An additional 2 (1.9%) had permanent neurologic deficits, and an additional 7 (6.5%) had transient neurologic deficits that resolved. Two patients developed pulmonary emboli, and 2 were returned to the operating room for postoperative bleeding.

Operative and in-hospital mortality was two out of 108 (1.9%). A total of 23 patients died during 7-year follow-up. Six patients succumbed to repeat sudden cardiac deaths and could not be resuscitated (Fig 1A, 1B). Three of these sudden deaths occurred in the CABG-only group. Of these, 2 patients were inducible on postoperative EP study but refused ICD placement, and 1 patient (seen in the first year of our experience) did not undergo postoperative EP study and did not receive further therapy. Three patients in the CABG plus medical antiarrhythmics group died of sudden death. Of these, 2 refused ICD placement, and 1 was seen in the first year of our experience. These are therefore not necessarily representative of our total experience with this group of patients. No patient who was noninducible on postoperative EP study died of sudden death, and no patient who underwent ICD placement after CABG died of sudden death.

There were eight complications related to ICD placement. Four patients failed to sense or pace and required lead revision. One patient had fracture of a lead requiring replacement. One patient had an elevated patch defibrillation threshold requiring endovenous lead placement. Two patients’ devices were unable to defibrillate and required revision to improve defibrillator threshold. All complications were detected during routine postoperative follow-up and none had serious consequences. There were no device infections.

Independent multivariate predictors of therapeutic ICD discharge included age >65 years (p = 0.01), reoperative CABG (p = 0.0003), LVEF <40% (p = 0.0007), and a positive postoperative EP study (p = 0.03) (Table 2). Of the 35 patients with ICDs, 9 patients had appropriate discharges (2 patients with CABG and ICD, and 7 patients with CABG, ICD, and medications). There were no inappropriate discharges. Patients who had no inducible arrhythmia after revascularization were free from subsequent sudden death or therapeutic discharge, regardless of ejection fraction.

View larger version (11K): [in this window] [in a new window]   Fig 2. Survival of patients with LVEF <40% undergoing CABG only or CABG with additional therapy (ICD or medical antiarrythmics). (CABG = coronary artery bypass grafting; ICD = internal cardioversion device; LVEF = left ventricular ejection fraction; meds = medications).

	Comment

Top Abstract Introduction Material and methods Results Comment References

The CABG Patch trial examined the role of CABG and ICD placement as primary prophylaxis against sudden cardiac death [14]. In this study, patients who were felt to be at a high risk of sudden death because of diminished LV function and abnormal signal-averaged electrocardiograms were randomized to CABG only and CABG plus ICD. It is important to note that patients with a preexisting history of sustained ventricular tachycardia or fibrillation were excluded from the study. Overall results showed a 7% increment in mortality (101 deaths in the defibrillator group and 95 in the control group, p = 0.64) over the course of the study. Post hoc analysis demonstrated a reduction in risk of sudden cardiac death with ICD in addition to CABG as compared with CABG alone [15].

These studies do not address the role of EP testing as a tool for patient stratification, the impact of ICD placement or medical therapy on influencing freedom from sudden death and survival after CABG in this particular patient population, and the adequacy of CABG alone for secondary prophylaxis of sudden cardiac death.

The role of EP testing in this population has remained uncertain. In the initial years of this study, it was common practice to assess the ability of medications to suppress arrhythmias in patients with a positive postoperative EP study. If medications succeeded in transforming a positive EP study to a negative one, patients were discharged with medications only and without an ICD. This practice is no longer common; nearly all of these patients would receive an ICD in the later years of the study.

Patients who suffered an arrest in the setting of vigorous exercise, with intact left ventricular function, did not always undergo postoperative EP testing, and many of them did not have an ICD either. As the evidence for the effectiveness of ICD therapy has accumulated, the burden of proof on the surgeon and cardiologist is considerable if an ICD is not used. As a result, the threshold for postoperative EP study is probably lower in current practice. In patients with diffuse coronary artery disease who would be incompletely revascularized or with a depressed ejection fraction, or whose arrest was clearly nonexertional, we reasoned that they should have ICD placed regardless, and therefore did not need EP testing after CABG.

Preoperative EP testing was not predictive of the need for ICD placement, recurrent sudden death, or increased mortality. This is consistent with prior studies that demonstrated that induction of ventricular fibrillation on preoperative EP testing is strongly predictive only of arrhythmia suppression after CABG [8]. Routine preoperative EP testing for survivors of sudden death who are to undergo CABG is not always helpful or necessary and may be contraindicated in patients with critical left main disease or unstable angina. Although CABG is known to suppress future ventricular arrhythmias, the ability to do so is unpredictable [16]. We recommend postoperative EP testing for patients who have any incremental risk for recurrent sudden death. Characteristics of this population include those greater than 65 years of age, female patients, those with Cleveland Severity Score greater than 8, patients requiring perioperative intraaortic balloon counterpulsation, those undergoing redo CABG, and those with LVEF <40%. Several of these predictors of increased risk have been documented in prior studies [17, 18]. The small number of patients who received ICDs based on preoperative EP studies but had negative postoperative studies remained free of device discharge. Inducibility at postoperative EP study was powerfully predictive of therapeutic device discharge. This has been documented in prior studies [19]. Patients who were not inducible at postoperative EP testing remained free of sudden death for the duration of this study.

This report suggests that CABG alone serves as adequate secondary prophylaxis in roughly half the patients studied. The addition of either ICD or medical management did not impact overall survival in this patient population when done selectively by the criteria described. That the four groups have similar survivals suggests prevention of death due to cardiac arrhythmia by ICD implantation or medical management appears to translate into a benefit in terms of overall survival not offset by competing causes of death in the high-risk population with severe ventricular dysfunction. Patients with ventricular dysfunction (LVEF <40%) are the only group to enjoy a powerful survival advantage with the addition of ICD and or medical antiarrhythmic therapy to CABG operation.

There are several limitations of our study. The first is the retrospective nature of this consecutive case series, in which treatment was not by protocol, and the approach to therapy changed in significant ways. The second is that there was case selection bias in that patients treated with medical antiarrhythmics or an ICD in addition to CABG were judged to be at greater risk of sudden death that those who underwent CABG alone. However, with the exception of ejection fraction (which was significantly worse in the groups receiving additional therapy), major prognostic factors such as age, perievent and remote cardiac history, associated medical conditions, extent and urgency of revascularization, and severity score were distributed evenly between the four groups. Third, as this study spans 12 years, an element of time selection bias may also influence the results with improvements in surgical and anesthetic technique, postoperative care, and ICD technology favoring patients who were treated later. Finally, the sample size is small, and several comparisons may have reached statistical significance if the cohort were larger. This can only be proved by larger prospective, randomized studies.

The survivor of cardiac sudden death who qualifies for ICD placement in addition to CABG needs to be better defined. The phenomenon of "indication creep" suggests that clinicians extrapolating data from the studies outlined above are increasingly prone to implant ICDs given their intuitive appeal (an approach that is not necessarily evidence based or cost-effective) [20]. In our opinion, survivors of prehospital cardiac arrest should be evaluated for the presence of coronary artery disease and treatable ischemia. An EP study before CABG surgery in these patients is not always helpful or necessary, and may be contraindicated in patients with critical left main disease or unstable angina. In the presence of reversible ischemia and appropriate anatomy, revascularization should be performed. This is adequate therapy for many patients. Patients should undergo postoperative EP study unless there are already definite indications for ICD implantation or if the original event was clearly provoked by ischemia and an ICD is felt to be unnecessary (for example, in a patient with normal left ventricular function and critical coronary disease who arrested during or soon after vigorous exercise). Patients over 65 years of age, those undergoing reoperative CABG, and those with left ventricular dysfunction have a higher risk of recurrent cardiac death or ICD discharge and should be considered for postoperative EP study. Any patient with a positive postoperative EP study should be treated with an ICD with or without concomitant medical antiarrhythmic management. ([13])

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Theodore J. Boeve Gus J. Vlahakes Cary W. Akins David F. Torchiana Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mangi, A. A. Articles by Torchiana, D. F. Search for Related Content PubMed PubMed Citation Articles by Mangi, A. A. Articles by Torchiana, D. F. Related Collections Electrophysiology - arrhythmias