(Circulation. 1995;92:73-79.)
© 1995 American Heart Association, Inc.
Articles |
From the Department of Surgery, University of Toronto (Ontario), Canada.
Correspondence to Dr L. Mickleborough, EN 13-217, The Toronto Hospital, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4.
| Abstract |
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Methods and Results In 79 consecutive patients (69 men, 10 women; average age, 59±9 years), preoperative ejection fraction was 18±5%. Indications for surgery were congestive heart failure (CHF) in 5 of 79 patients (6%), CHF and angina in 19 (24%), angina in 41 (52%), ventricular arrhythmias (VAs) in 8 (10%), and critical anatomy in 6 (8%). Some patients had prior VAs (23 of 79; 29%) or mitral regurgitation (18; 23%) and required emergent surgery (25; 32%). At surgery, temperature mapping ensured adequate distribution of antegrade cold cardioplegia, with 3.6±0.7 grafts per patient, including left internal mammary artery graft in 60 of 79 (76%) and endarterectomy in 14 (18%). Hospital mortality was 3.8%. Perioperative support included intra-aortic balloon pump in 18 of 79 (23%) and drugs for VAs in 28 (35%). Morbidity included myocardial infarction in 2 of 79 (2.5%) and stroke in 2 (2.5%). During follow-up, there were 19 late deaths. Actuarial survival was 94%, 82%, and 68% at 1, 2, and 5 years, respectively, and was similar in patients with severe angina, CHF, mitral regurgitation, or VAs. Freedom from sudden death was 100%, 98%, and 91% at 1, 2, and 5 years, respectively. Among survivors, angina improved in 84% and heart failure improved in 26%.
Conclusions These data support bypass graft surgery in patients with severe LV dysfunction. With careful cardioplegic techniques, hospital mortality was low (3.8%). Long-term survival is encouraging, with good relief of symptoms in most patients. Perioperative VAs are frequent but respond to medical treatment, with only 23% of patients discharged on antiarrhythmic drugs. Five-year freedom from sudden death is 91%, with only 3 late sudden deaths in this series.
Key Words: bypass ventricles arrhythmia
| Introduction |
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In patients with coronary artery disease and poor LV function, revascularization should be considered as a treatment option. In those with prior MI and resectable scar, the benefits of revascularization and scar excision, which can be accomplished with a low operative mortality, have been well established.5 6 In those with severe generalized LV dysfunction (EF, <20% with no clearly resectable scar), aortocoronary bypass graft surgery has in the past been associated with increased operative mortality, and some authors consider the risks prohibitive.7 Recently, however, improvements in anesthesia, myocardial protection, and postoperative support have decreased the operative mortality in this group.8 9 10
However, little is known about long-term survival in these patients. In a recent study, Lansman et al11 reported survival of only 68% at 3 years and 34% at 6 years. This study suggested that those patients with symptoms of severe angina were most likely to survive long-term. Preoperative CHF and ventricular arrhythmias appeared to be related to poor long-term results in their series.
The present study was undertaken to review results of coronary bypass graft surgery in patients with an EF of <20%. Included in this series were patients with CHF and ventricular arrhythmias, as well as those presenting primarily with anginal symptoms. We used a technique of temperature-guided antegrade cardioplegia delivery that we think ensures optimal myocardial protection. In this series, indications for surgery, operative mortality, complications, improvement in symptom status, and late results have been reviewed in different subgroups and compared with available data from the literature.
| Methods |
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20% defined by cineangiography and were
included in this study. The hospital records of these patients were
reviewed by trained chart reviewers using a standard data collection
form.
Clinical Presentation
Preoperative clinical variables,
including sex, age, history
of prior MI, anginal pattern, history of ventricular
arrhythmias, diabetes, smoking history, hypertension, family
history for coronary artery disease, peripheral
vascular disease, symptom class with respect to angina (CCS) and heart
failure (NYHA), and timing of surgery, were prospectively gathered and
evaluated. The timing of operation was designated as elective
(including operation on the same admission) or emergent (OR from CCU or
catheterization laboratory with an acutely unstable
patient). Patients with a history of ventricular
arrhythmias were classified as to the type of
arrhythmia (PVC versus VT/VF) and relationship of the
arrhythmic event to acute MI.
Catheterization Data
Cardiac catheterization was performed in
all
patients to assess ventricular function and the extent of
coronary artery disease. The LVEF was estimated by a
single-plane ventriculogram. Coronary narrowing
50% was
considered significant. Factors derived from cardiac
catheterization on each patient included the number of
diseased vessels, the number of vessels occluded with inadequate distal
visualization (questionably graftable), and EF. In some patients with a
history of ventricular arrhythmias, a preoperative
electrophysiological study was performed as
previously described.12
Operative Technique and Intraoperative Data
Fentanyl citrate
was used for induction and
maintenance of anesthesia. Our cardioplegia
technique consisted of antegrade delivery of cold cardioplegia
(crystalloid from 1982 through 1983 and blood from 1983 through 1993).
After the initial dose of cold cardioplegia, myocardial temperatures in
three major distributions have been measured with a needle thermistor.
In cases of uneven cooling (regional temperature >18°C), a graft was
constructed to the warm area first (diagonal in the case of LAD disease
with planned use of a left internal mammary artery), and additional
doses of cardioplegia were given down the completed graft, as well as
into the aortic root, to achieve adequate cooling. Since 1985, a
terminal "hot shot" has been used.13
Between 1982 and 1989, systemic hypothermia (25°C) was used. Since 1989, body temperature has been allowed to drift (it usually falls to 32°C during the cross-clamp period), and no active cooling, either systemic or topical, has been used.
Since 1984, use of the internal mammary artery has increased dramatically. Proximal vein anastomoses have been performed during a single period of cross-clamping. Information obtained from the anesthetic and OR records includes postinduction pulmonary artery diastolic pressure, cardiac index, stroke-work index, number of grafts performed, number of endarterectomies, pump time, and cross-clamp time.
Postoperative Care and Outcome
Postoperative mortality and
morbidity were reviewed.
Operative mortality was defined as death within 30 days of operation or
during hospital stay. Preoperative and postoperative ECGs were reviewed
by a cardiologist who was not involved with clinical care of the
patient. Perioperative MI was defined by the appearance
of a new Q wave on the ECG or an elevation in CK enzyme, with CKMB >50
U/L or >8% of the total CK.10 Low cardiac output
syndrome was defined by requirement for inotropic medication for >30
minutes to maintain systolic blood pressure >90 mm Hg and cardiac
index >2 L ·min-1 · m-2 or
when
an intra-aortic balloon pump was required to sustain the
circulation.10 A postoperative stroke was diagnosed if a
persistent neurological deficit was present at the time of
discharge. Sternal wound infection was diagnosed if prolonged
hospitalization was required because of antibiotic therapy or sternal
rewiring. Postoperative arrhythmias were considered significant
if they required treatment for >24 hours and were classified as PVCs
or VT/VF. Follow-up was performed in 1994 by means of telephone
contact with patients or referring physicians plus office visits when
indicated. Follow-up was achieved in all patients, although
definite cause of death was not always known.
Statistical Analysis
The SAS (SAS Inc) and
BMDP (BMDP
Software) programs were used for statistical analysis.
Predictors of mortality were determined by univariate and
multivariate techniques. For univariate
analysis, discrete data were analyzed with
2 test or Fisher's exact test, as appropriate.
Variables that were significant by univariate
analysis were entered into the multivariate
analysis by Cox regression. Statistical significance was
assumed when the probability value was P<.05. Kaplan-Meier
survival curves were constructed and were compared by Mantel-Cox test
for different patient subgroups.
| Results |
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Associated comorbid factors included diabetes in 18%, hypertension in 41%, and peripheral vascular disease in 18%. Seventy-six percent of patients had a prior smoking history, 33% had hyperlipidemia, and 57% had a family history of coronary artery disease.
Preoperative arrhythmias were documented in 23 of 79 (29%). In 14 of 79 (18%), there was a history of VT/VF at the time of a prior MI. In 9 of 79 (11%), spontaneous VT/VF occurred at a time remote from an acute MI. Three of these patients underwent a preoperative electrophysiological study, and VT was inducible in all 3. In an additional 8 of 79 (10%), antiarrhythmic medications had been prescribed previously, but a detailed history of ventricular arrhythmias could not be obtained. Fifteen of 79 patients (19%) were on antiarrhythmic medications at the time of surgery (procainamide in 6, amiodarone in 7, and propafenone in 2).
Angiographic descriptors of the patient
population are given in Table 2
. All patients had double- or
triple-vessel
disease, and 13% had significant left main-stem stenosis.
Thirty-nine of 79 (49%) had at least one vessel totally occluded,
with poor distal visualization, making the possibility of grafting in
this distribution uncertain. Twenty-three percent of patients had
mild to moderate mitral regurgitation (2 to 3+) at the
time of preoperative angiographic or echocardiographic
assessment. At catheterization, the average LVEDP was
23±9 mm Hg, and average EF was 18±5%.
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At surgery, the average pulmonary artery diastolic pressure, cardiac index, and LV stroke-work index were 15.4±4.5 mm Hg, 2.4±0.5 L · min-1 · m-2, and 32.6±8.1 g · m/m2. Three of 79 (4%) were on intra-aortic balloon support when transferred to the operating room. An average of 3.6±0.7 grafts were performed per patient. In 60 of 79 (76%), a mammary graft to the LAD was constructed, and coronary endarterectomy was required in 14 of 79 (18%). Average cross-clamp time was 60±16 minutes (range, 30 to 111 minutes), and the average pump time was 115±30 minutes (range, 60 to 198 minutes).
Early Results
Operative mortality was 3.8% (3 of 79). Deaths
were due to adult
respiratory distress syndrome associated with chronic
amiodarone therapy (1 patient) and CHF with low-output
syndrome (2 patients). No hospital deaths were related to
ventricular arrhythmias. Low-output syndrome
occurred in 20 of 79 patients (25%), and 18 of 79 (23%) required
perioperative intra-aortic balloon support (this
figure includes preoperative insertion). Antiarrhythmics were required
briefly (<24 hours) to suppress PVCs in 12 of 79 (15%). Prolonged
treatment with antiarrhythmic agents was required in an additional 28
of 79 (35%): in 18 (23%) for PVCs and in 7 (9%) for VT/VF; in 3
(4%), drugs were given prophylactically because of a prior
history of VT/VF. Eighteen of 79 (23%) were discharged on
antiarrhythmic medications (8 on procainamide, 9 on
amiodarone, and 1 on mexiletine). Other postoperative
complications included perioperative MI in 2 (2.5%),
stroke in 2 (2.5%), sternal wound infection in 1 (1.3%), leg
infection in 2 (2.5%), and reoperation for bleeding in 1 (1.3%).
Late Results
During follow-up, which extends from 1 month to
11 years,
(mean, 44±34 months), there have been 19 late deaths: 3 sudden deaths,
10 nonsudden cardiac deaths, 2 deaths due to cancer, and 4 deaths of
unknown cause. Actuarial survival at 5 years is 68%, and freedom from
sudden death is 91% (Fig 1
). Of the 3 patients who died
suddenly, 2 had a history of PVCs at the time of prior MI, and because
of perioperative PVCs, they were discharged on
procainamide. The other sudden death occurred in a patient who
had no history of preoperative ventricular
arrhythmias, no need for antiarrhythmic medication during the
perioperative period, and no history of
arrhythmias during follow-up.
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By univariate analysis, only two
variables were
found to adversely affect long-term survival: age >70 years and
peripheral vascular disease. By
multivariate logistic regression analysis, only
age >70 years predicted decreased survival. Other variables such
as presence or absence of angina, severity of angina or CHF, or
presence or absence of ventricular arrhythmias had
no significant effect on long-term survival (Fig 2
).
Presence or absence of preoperative mitral
regurgitation also had no significant effect on
long-term survival (Fig 3
).
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Fig 4
compares preoperative and postoperative symptom
status for angina and CHF among survivors. Mean anginal class improved
from 3.2±1.0 preoperatively to 1.5±0.8 postoperatively, and 84%
of
patients were improved by at least one CCS class. CHF symptoms were
improved by at least one NYHA class in 26% of patients; however, there
was no significant change in the mean CHF class before compared with
after operation: 1.9±1.1 versus 1.9±1.1.
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During follow-up, 28 of 57 survivors (49%) have required rehospitalization. In 11 (19%), this was for noncardiac problems. Seventeen patients (30%) required readmission for cardiac reasons: 12 for CHF (including 2 MI) and 5 for arrhythmias (2 for atrial fibrillation). No patient has been referred for transplantation or mitral valve replacement. Permanent pacemakers have been implanted in 2 patients for bradyarrhythmias. No patient in this series was referred for implantation of an AICD.
| Discussion |
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An alternative treatment for some of these patients that is very effective is cardiac transplantation. Currently, ischemic heart disease accounts for 40% to 50% of transplants performed.16 17 Many patients with coronary disease are referred for transplantation because of "inoperability" based on "prohibitive" ventricular function or poor quality of distal vessels. Although transplantation is associated with excellent functional results and a 5-year survival of 70% to 80%,14 15 there has been a plateau in the number of transplants performed because of limited donor availability.16 18 Only 10% of eligible patients will actually undergo transplantation,19 and many patients will die on the waiting list. In those considered "not sick enough" to get on the transplant list, the 2- to 3-year survival with medical therapy is very poor.20 Clearly, in these patients revascularization should be considered an option whenever possible.
Results of this study support the use of coronary artery bypass
graft surgery in patients with low EF (<20%). We have shown that in
these patients, the operation can be performed safely (hospital
mortality, 3.8%) and results in satisfactory long-term survival:
94% at 1 year, 82% at 2 years, and 68% at 5 years. These results
compare favorably with those from other recent series. Elefteriades et
al21 reported a hospital mortality of 8.4% and a 3-year
survival of 80% in patients with an EF
30%. Kron et
al8 reported a hospital mortality of 2.6% and a 3-year
survival of 83%.
There are very few studies that report long-term follow-up after revascularization in patients with this degree of ventricular dysfunction. Johnson et al22 reported survival of only 50% at 5 years but included in their series patients undergoing redo operations. Lansman et al11 reported a hospital mortality of 4.8%, with an 88% survival at 1 year, 68% at 3 years, and 34% at 6 years. Milano et al,23 in a series of patients with an EF <25%, reported a hospital mortality of 11% and 1- and 5-year survivals of 77% and 58%, respectively. Our 5-year survival of 68% compares favorably to these figures. Clearly, case selection as well as anesthetic and cardioplegic techniques may account for these differences in operative mortality and long-term survival. We need to further define preoperative variables that are predictive of a good outcome after revascularization in patients with poor LV function.
When the role of revascularization in patients with poor LV function is considered, the concept of hibernating myocardium proposed by Rahimtoola24 25 is an important one. This concept states that chronic ischemia can lead to reversible cardiac dysfunction, which will improve with restored perfusion. In assessment of patients with poor LV function as possible candidates for revascularization, there has been a great deal of interest in trying to establish methods that will allow us to evaluate the presence of viable but hibernating myocardium. Suggested markers for reversible ischemia include symptom status, ie, anginal response to nitrates,26 evidence of reversible ischemia on redistribution thallium scanning,27 or positron emission tomographic scanning28 or evaluation of potentiation of ventricular contraction with extrasystoles29 or inotrope infusion.30 At present, there is little or no information on whether better patient selection based on these tests will improve long-term results with revascularization in patients with poor ventricular function. In our series, only a small number of patients underwent redistribution thallium scanning, and like Kron et al8 and Louie et al,14 we found that results of this test were insensitive in detecting the presence of viable myocardium and did not predict which patients would improve symptomatically.
In patients with coronary artery disease and poor LV function, it is often difficult or impossible, on the basis of the preoperative ventriculogram, to determine what areas of the heart will benefit from revascularization and what areas have undergone significant scarring and thinning, in which case excision of the noncontractile wall and LV remodeling5 may be of more benefit. We feel that in patients with poor LV function and an area of akinesis or dyskinesis, the choice to resect scar or to revascularize hibernating myocardium can best be determined at the time of surgery. If the area is significantly scarred and thinned, we proceed with scar excision (such patients were excluded from this series). Our results with this approach have been described previously.5 In patients in whom the akinetic or dyskinetic area corresponds to a thick region of myocardium mixed with scar, revascularization was carried out. Either way, surgery has something to offer.
Cardioplegia Techniques
In patients with severe triple-vessel
disease, it has been
shown that antegrade cardioplegia delivery often leads to inadequate
distribution.31 32 33 34 35
With cold cardioplegia, measurement of
regional temperatures can be used to assess adequacy of
delivery,36 37 and it has been recommended that the
sequence of vessel grafting should be determined by "temperature
mapping."36 38 39 We have used this
technique of
myocardial preservation and believe this has contributed to our low
perioperative infarction rate (2.5%) and low hospital
mortality (3.8%). Our results can be compared with a hospital
mortality of 9.8% previously reported in a large overlapping series of
similar patients from Toronto in whom a variety of cardioplegic
techniques were used.10
Quality of Life and Predictors of Long-term
Survival
We agree with Elefteriades et al21 that
improvement in both anginal status and CHF status can be achieved with
revascularization in patients with poor
ventricular function (84% improved by one or more anginal
class and 26% improved by one or more CHF class, Fig 4
). In our
series, the only predictors of decreased long-term survival were
age >70 years and associated peripheral vascular disease.
Other factors identified in previous series as predicting poor outcome,
including female sex, hypertension, preoperative elevation in LVEDP, or
decreased cardiac index, were not related to mortality in this
series.11 23 40 In our experience,
long-term survival
was not different for patients in the following subgroups: those with
or without angina, with or without severe CHF, with or without mild to
moderate mitral regurgitation, and with or without a
history of ventricular arrhythmias (Fig 2
).
Our results agree with other reports, including the CASS study, that showed that coronary artery bypass graft surgery, compared with medical therapy, was associated with increased longevity, which was most impressive in those with poor LV function (EF <30%)41 42 43 and that this improved survival occurred in patients with or without anginal symptoms.44 Our results do not support the previous recommendation that the absence of significant angina or presence of significant heart failure should mitigate against bypass graft surgery in patients with poor LV function.11 45 46 47 48 In the small group of patients in our series with evidence of mitral regurgitation on preoperative evaluation (n=18), 5 died during follow-up after a mean of 3.5 years. Of survivors, only 2 of 13 required readmission to hospital for symptoms of CHF or arrhythmias.
Ventricular Arrhythmias
In patients with coronary artery
disease and poor LV
function, insertion of an AICD has proved effective in decreasing the
incidence of sudden death. However, in patients with a low EF, the
operative risks for device insertion are increased,49 and
long-term survival in current reported series is limited (<60% at
3 years), with most deaths related to progressive
CHF.50
In our center, most patients with coronary artery disease, a history of VT/VF, and inducible VT undergo map-directed VT ablation at the time of revascularization.51 Only those considered to be at increased risk for mapping undergo revascularization alone and are included in this series. There were 9 patients in this series with VT/VF not associated with acute infarction. In these patients, the reasons for not performing map-directed surgery were age >65 years in 6, noninducibility of VT at electrophysiological study in 1, and lack of transmural scar to allow endocardial ablation in 2. Results of revascularization in these 9 patients are as follows. One patient who had been on chronic amiodarone therapy before surgery died of severe adult respiratory distress syndrome on day 7 after surgery without any recurrence of ventricular arrhythmias. Two patients had recurrent VT perioperatively and were treated with amiodarone. One of these patients died of CHF 2 years after surgery, and the other is alive 10 months after surgery. Four patients in this group had no ventricular arrhythmias after surgery but were discharged on amiodarone because of the history of VT/VF. One died of CHF 20 months after surgery, and the other 3 are alive and free of arrhythmia at 3 years, 3 years, and 8 years after surgery, respectively. The remaining 2 patients in this group had PVCs postoperatively; one was treated with mexiletine, and the other was treated with procan. Both are alive at 2.5 and 5.5 years after surgery.
In this series, ventricular arrhythmias were common after surgery, with 21 other patients (26%) requiring drug therapy (>24 hours). Of these, 10 were discharged on antiarrhythmic drugs. There were no hospital deaths due to arrhythmias.
During follow-up, there were 3 sudden deaths in this series. Two occurred in patients with a history of PVCs at the time of a prior MI who had PVCs postoperatively and were discharged on procainamide. The third sudden death occurred in a patient with no prior history of ventricular arrhythmias. Also during follow-up, 3 patients were admitted because of ventricular arrhythmias. One patient had no history of prior ventricular arrhythmias, 1 had no preoperative history of arrhythmias but had developed PVCs postoperatively and was discharged on procainamide, and a third patient had a history of ventricular arrhythmias at the time of a preoperative MI, had no arrhythmias postoperatively, and was discharged on no antiarrhythmic drugs. In these 3 patients, the arrhythmias were successfully treated with amiodarone. No patient in this series received an AICD.
In the literature, ventricular arrhythmias are a common cause of OR mortality and death during follow-up in patients undergoing revascularization with EF <20%. In the series by Kron et al,8 7 of 8 late deaths were due to ventricular arrhythmias, and in the series by Milano et al,23 ventricular arrhythmias were the most frequent cause of OR mortality, accounting for 6 of 13 deaths. Lansman et al11 reported, in 42 patients, 4 hospital deaths and 8 late deaths due to arrhythmias. However, both Milano et al and Lansman et al noted that the presence of preoperative arrhythmias did not predict long-term survival. Elefteriades et al21 inserted an AICD at the time of revascularization in 28 of 83 patients and concluded that the presence of the device might have contributed to long-term survival (80% at 3 years). In our center, patients with a history of spontaneous VT/VF are considered candidates for revascularization and map-directed VT ablation if at all possible. In those patients with poor ventricular function undergoing revascularization alone, ventricular arrhythmias were treated aggressively, and amiodarone was often used as the drug of choice. This aggressive approach in managing arrhythmias may explain our results, with no arrhythmic hospital deaths and only 3 late sudden deaths in this series.
In these patients, we proceeded with aortocoronary bypass graft surgery even when there was uncertainty of complete revascularization. In 24 of 79 patients (30%), the right coronary artery was blocked and poorly visualized distally. In 22 of 24 patients, the distal vessel was grafted, although endarterectomy was required in 8. In 12 of 79 (15%), the LAD was blocked, with poor distal visualization, and in all 12 the distal vessel was grafted. In 10 patients (13%), the circumflex was blocked, with poor distal visualization. In 8 of 10, the distal vessel was grafted. We used the internal mammary artery in the majority of patients (76%). We agree with Elefteriades et al21 that use of the internal mammary artery is not contraindicated in such patients, as has been suggested.52
Our results support the use of aortocoronary bypass graft surgery in patients with poor LV function (EF <20%) and no resectable scar. If careful cardioplegia techniques are used, the procedure can be performed with a low operative mortality (3.8%) and will provide good relief of symptoms in most patients. In our experience, long-term survival is encouraging (actuarial survival, 68% at 5 years) and is not different in patient subgroups with or without angina, CHF, mitral regurgitation, or prior history of ventricular arrhythmias. Although postoperative ventricular arrhythmias are frequent in these patients, there were no hospital deaths due to arrhythmias, and only 23% of patients were discharged on antiarrhythmic drugs. Freedom from sudden death is 91% at 5 years, with only 3 sudden deaths in this series.
| Selected Abbreviations and Acronyms |
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| Acknowledgments |
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| References |
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