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Anesth Analg 2002;95:1483-1488
© 2002 International Anesthesia Research Society

CARDIOVASCULAR ANESTHESIA

The Association Between Heart Rate and In-Hospital Mortality After Coronary Artery Bypass Graft Surgery

Mary P. Fillinger, MD*, Stephen D. Surgenor, MD MS*, Gregg S. Hartman, MD*, Cantwell Clark, MD, Thomas M. Dodds, MD*, Athos J. Rassias, MD*, William C. Paganelli, MD**, Peter Marshall, MD#, David Johnson, MD, Dennis Kelly, MD{ddagger}, Dean Galatis, MD§, Elaine M. Olmstead, BA{dagger}, Cathy S. Ross, MS&Verbar||, and Gerald T. O’Connor, PhD DSc|||| for the Northern New England Cardiovascular Disease Study Group

Departments of *Anesthesiology and {dagger}Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire; {ddagger}Department of Anesthesiology, Catholic Medical Center, Manchester, New Hampshire; §Department of Anesthesiology, Concord Hospital, Concord, New Hampshire; &Verbar||Dartmouth Medical School, Hanover, New Hampshire; ¶Department of Anesthesiology, Maine Medical Center, Portland, Maine; #Department of Anesthesiology, Central Maine Medical Center, Lewiston, Maine; and **Department of Anesthesiology, Fletcher Allen Health Care, Burlington, Vermont

Address correspondence and reprint requests to Mary P. Fillinger, MD, Department of Anesthesiology, One Medical Center Drive, Lebanon, NH 03756. Address e-mail to mary.p.fillinger{at}hitchcock.org


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Avoidance of tachycardia is a commonly described goal for anesthetic management during coronary artery bypass graft (CABG) surgery. However, an association between increased intraoperative heart rate and mortality has not been described. We conducted an observational study to evaluate the association between preinduction heart rate (heart rate upon arrival to the operating room) and in-hospital mortality during CABG surgery. Data were collected on 5934 CABG patients. Fifteen percent of patients had an increased preinduction heart rate >=80 bpm. Crude mortality was significantly more frequent among patients with increased preinduction heart rate (Ptrend = 0.002). After adjustment for baseline differences among patients, preinduction heart rate >=80 bpm remained associated with increased mortality (Ptrend < 0.001). The increased heart rate may be a cause of the observed mortality. Alternatively, faster heart rate may be either a marker of patients with irreversible myocardial damage, or a marker of patients with limited cardiac reserve at risk for further injury. Lastly, faster heart rate may be a marker for under-use of ß-adrenergic blockade. Because the use of preoperative ß-adrenergic blockade in CABG patients is associated with improved in-hospital survival, further investigation concerning the effect of intraoperative treatment of increased heart rate with ß-adrenergic blockers on mortality after CABG surgery is warranted.

IMPLICATIONS: We conducted an observational study to evaluate the association between heart rate upon arrival to the operating room (preinduction heart rate) and in-hospital mortality during coronary artery bypass graft surgery. After adjustment for baseline differences among patients, preinduction heart rate >=80 bpm was associated with an increased in-hospital mortality after coronary artery bypass graft surgery.


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Tachycardia in the presence of coronary artery disease has deleterious effects on both myocardial oxygen supply and demand (1). In 1988, Slogoff and Keats (2) observed that the incidence of myocardial ischemia was increased among tachycardic patients undergoing coronary artery bypass graft (CABG) surgery. Their sample size, however, was inadequate to document a statistically significant relationship between tachycardia and mortality. More recently, Reich et al. (3) observed the association of tachycardia with mortality and myocardial infarction among 2149 CABG patients at 2 hospitals in the New York State Department of Health Cardiac Study Reporting Program database during 1993 to 1995. They observed that precardiopulmonary bypass (CPB) heart rates faster than 100 bpm were associated with an increased risk of myocardial infarction but not mortality. Although these data further support the notion that a faster heart rate increases the risk of myocardial ischemia, a clear demonstration of an association between increased pre-CPB heart rate and increased mortality after CABG surgery has not been well described.

Pre-CPB heart rate is an easily identified hemodynamic variable that can be treated pharmacologically. If increased heart rate has a causal association with mortality, then more aggressive prevention and treatment may lead to a reduction in mortality after CABG surgery. In a randomized trial, the Multicenter Study of Perioperative Ischemia Research Group documented a reduction in mortality with the perioperative use of the ß-adrenergic blocker atenolol during noncardiac surgery (4). There is also evidence for the benefit of ß-blockade before CABG surgery. Weightman et al. (5) observed a reduction in the risk of mortality associated with preoperative ß-adrenergic blockade among 1593 CABG patients in Australia. More recently, Ferguson et al. (6), using the Society of Thoracic Surgery National Adult Cardiac Surgery Database, reported that preoperative ß-blockade was associated with a survival benefit among 629,877 patients undergoing isolated CABG.

Avoidance of tachycardia is a commonly described goal for anesthetic management during CABG surgery (1,7). However, increased heart rate remains a common event during CABG surgery. For example, Urban et al. (8) observed that 15% of 100 CABG patients had heart rates >80 bpm during the preinduction period. We conducted a prospective, observational study to evaluate the association between preinduction heart rate (heart rate upon arrival to the operating room) and in-hospital mortality among patients undergoing CABG surgery.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
The Northern New England Cardiovascular Disease Study Group (NNECDSG) is a regional voluntary consortium with the mission to develop and exchange information concerning treatment of cardiovascular disease. The NNECDSG consists of clinicians, hospital administrators, and health care research personnel who seek to continuously improve the quality, safety, effectiveness, and cost of medical interventions in cardiovascular disease. The Group maintains continuing prospective registries of all patients receiving percutaneous transluminal coronary angioplasty, CABG, and heart valve repair or replacement surgery. Six of the medical centers in the NNECDSG participated in the current study. These centers were Catholic Medical Center, Concord Hospital, Dartmouth-Hitchcock Medical Center, Eastern Maine Medical Center, Fletcher Allen Health Care, and Maine Medical Center. This study was approved by the IRBs of all participating centers.

Data were prospectively collected on 5934 patients having isolated CABG procedures between January 1995 through June 2000. Patients who had isolated valve or combined valve/CABG surgery were excluded from this study. Data on the following preoperative characteristics were collected: age, sex, body surface area, diabetes mellitus, chronic obstructive pulmonary disease, peripheral vascular disease, congestive heart failure, dialysis-dependent renal failure, last preoperative serum creatinine, and prior CABG surgery. Diabetes was defined as documentation of this disease state in the patient history or medical record. Chronic obstructive pulmonary disease was defined as obstructive lung disease or asthma requiring treatment with inhalers, theophylline, or steroids. Congestive heart failure was defined as documentation of exertional dyspnea, fatigue, bilateral pedal edema, orthopnea, paroxysmal nocturnal dyspnea, acute pulmonary edema, or rales during or before admission. Preoperative cardiac catheterization results included left ventricular ejection fraction (LVEF), left ventricular end-diastolic pressure (LVEDP), number of diseased coronary arteries, and stenosis of the left main coronary artery. Left main coronary disease was defined as >50% stenosis. Priority at surgery was classified as emergency, urgent, or elective. Emergency surgery required that medical factors relating to the patient’s cardiac disease dictate that surgery should be performed within hours to prevent morbidity or death. Urgent surgical status required that the patient had to stay in the hospital before operation because of medical factors.

Preinduction heart rate was defined as heart rate upon arrival to the operating room and was obtained directly from the electrocardiogram after standard lead placement by the anesthesiologist. In most cases, the heart rate was obtained after preoperative sedation had been given. IV sedation typically consisted of fentanyl 1-2 µg/kg and midazolam <=0.05 mg/kg. In the case of dysrhythmias, preinduction heart rate was the average heart rate after a stabilization period. Patients were divided into 6 groups by their preinduction heart rate (<50, 50–59, 60–69, 70–79, 80–89, and >=90 bpm) The main outcome for this study was in-hospital mortality. In addition, the use of an intraaortic balloon pump (IABP) intraoperatively or postoperatively, return to CPB after initial complete separation from CPB, and cerebrovascular accident were collected and examined. Cerebrovascular accident was defined by the following: new focal neurologic deficit that appears and is still at least partially evident >24 h after its onset, occurring during or after the CABG procedure and established before discharge.

Outcome rates were adjusted by using both multivariate logistic regression and direct standardization techniques. Logistic regression models were used to calculate the predicted risk of adverse outcomes associated with CABG surgery for each patient in the registry. In addition to the outcome variables, the models use the following factors to calculate predicted risk: patient age, sex, body surface area, chronic obstructive pulmonary disease, diabetes, peripheral vascular disease, preoperative congestive heart failure, preoperative renal failure, or serum creatinine >2 mg/dL, prior CABG surgery, preoperative LVEDP, preoperative LVEF, left main coronary artery stenosis, number of diseased coronary vessels, and priority at surgery. Using risk information from the models, a risk profile for all patients in the dataset was created. By direct standardization methods, and using the risk profile for all patients and actual rates for each heart rate category, adjusted rates were calculated that represented what the rates would be if all patients were similar in risk. In this way, outcome rates by heart rate category could be compared without the confounding effects of varying case mix. The nonparametric test for trend across ordered groups that we used is the Cuzick extension of the Wilcoxon’s ranked sum (9). Statistical analysis was performed by using STATA software (10).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
The distribution of preinduction heart rates for the 5934 patients is shown in Figure 1. The majority of patients (72%) had heart rates between 50 and 79 bpm upon arrival to the operating room. Fifteen percent had a heart rate of >=80 bpm and 5.0% (n = 275) of the patients had a preinduction heart rate of >=90 bpm. There were several significant differences in patient and disease characteristics across the preinduction heart rate groups (Table 1). Women composed a larger proportion of the faster heart rate categories (38.6% of those with a heart rate >=90 bpm versus 17.0% with a heart rate <50 bpm). The patients in the fastest heart rate categories were younger by an average of 1 to 3 yr compared with the other groups. In addition, there were increased percentages of patients with chronic obstructive pulmonary disease, diabetes, congestive heart failure, and urgent and emergent surgical status across increasing heart rate groups. Mean LVEF decreased and mean LVEDP increased across the groups.



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  		Figure 1. Preinduction heart rates.

 

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  		Table 1. Patient and Disease Characteristics and In-Hospital Outcomes by Preoperative Heart Rate Category
 
Crude mortality increased significantly with increased preinduction heart rate (Fig. 2). To evaluate whether this trend was attributed to differences in patient characteristics, mortality rates for the six groups were adjusted for patient and disease characteristics. After adjustment, a significant trend of increasing rate of mortality with increasing preinduction heart rate was still observed (Ptrend < 0.001) (Fig. 2).



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  		Figure 2. Preinduction heart rate (HR) and in-hospital mortality crude and adjusted rates. *Event rates adjusted for age, sex, body surface area, chronic obstructive pulmonary disease, diabetes mellitus, peripheral vascular disease, preoperative congestive heart failure, preoperative renal failure or creatinine >2 mg/dL, prior coronary artery bypass graft surgery, preoperative left ventricular end diastolic pressure, preoperative ejection fraction, left main stenosis, number of diseased coronary arteries, and priority at surgery.

 
Among the 5934 patients in this study, CABG was performed by using CPB in 5399 patients whereas 535 patients had their procedures without CPB. The latter group was distributed evenly across the heart rate categories (between 7% and 10% of each heart rate group were off-CPB procedures). A separate group analysis demonstrated the same association between preinduction heart rate and mortality whether CABG was performed on or off CPB.

There was no significant association of preinduction heart rate and frequency of postoperative stroke (Ptrend = 0.146) (Table 2). There was a significant trend of increased frequency of intraoperative IABP use (Ptrend = 0.002). No significant trend was observed for frequency of return to CPB.


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  		Table 2. Preinduction Heart Rate and In-Hospital Outcomes Risk Adjusteda Rates
 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
We observed that a heart rate >=80 bpm before the induction of anesthesia for CABG surgery was associated with a statistically significant increased risk of in-hospital mortality. This increase in risk remained statistically significant after adjustment for patient and disease characteristics including: age, sex, body surface area, chronic obstructive pulmonary disease, diabetes, peripheral vascular disease, preoperative renal failure or creatinine >2 mg/dL, prior CABG, preoperative LVEDP and LVEF, left main coronary stenosis, number of diseased coronary arteries, and priority at surgery. Patients in the fastest heart rate groups (80–89, >=90 bpm) had mortality rates 2–3 times as high as those in the slowest preinduction heart rate groups. We also observed that the intraoperative use of IABP increased with faster preinduction heart rates. These data suggest that low output heart failure may contribute to the relationship for the association of increased heart rate and in-hospital mortality.

This was an observational study and therefore the results are vulnerable to chance, bias, and confounding. However, the sample size is large, and the results are highly significant. The definitions and methods of data collection were uniform at the participating centers. The findings persisted even after multivariate adjustment for differences in patient and disease characteristics. Importantly, this study represents observation of routine daily care of all patients presenting for CABG surgery at these centers. This was not an intervention or treatment study, and our observations do not provide proof that prevention or treatment of increased heart rates would improve mortality.

Increased heart rate may be the cause of the excess observed mortality on the basis of demand myocardial ischemia. Alternatively, increased heart rate may merely be a marker of patients with limited cardiac reserve at risk for further injury, or of patients with irreversible myocardial injury. For example, 15.3% of emergent patients in the study population with preinduction heart rates of >=80 bpm subsequently died. Many of these emergent operations are performed to manage acute coronary insufficiency, and increased heart rate in this setting may be a compensatory response. In this scenario, preoperative management of increased heart rate may not be feasible or wise (11).

Preinduction heart rate of >=80 bpm may represent a subset of patients in whom ß-adrenergic blockade is either not used or subtherapeutic if used. There were disproportionate percentages of patients with chronic obstructive pulmonary disease, diabetes, congestive heart failure, and depressed LVEF in the faster heart rate groups. Despite data demonstrating that patients with chronic heart failure and depressed LVEF had improved survival when treated with ß-blockers (11), these comorbidities have been considered relative contraindications to the use of ß-adrenergic blockade in the past. The NNECDSG did not collect information about the preoperative use of ß-blockers during this study period. Therefore, it is unknown whether the overrepresentation of patients with chronic lung disease, diabetes, heart failure, and depressed LVEF in the faster heart rate group was attributable to under-use of ß-adrenergic blockade. Overall, however, two-thirds of the patients with heart rates of >=80 bpm did not have any of these comorbid conditions. Indeed, many of these patients may have been eligible for, but did not receive, preoperative ß-adrenergic blockade.

Determining the relationship of preoperative ß-blockade to preinduction heart rate, particularly among patients with these comorbidities, will be an area for further investigation in the NNECDSG. The use of preoperative ß-blockade to decrease mortality associated with CABG is supported by the observations of both Weightman et al. (5) and Ferguson et al. (6). In the latter study, the adequacy of preoperative ß-blockade was not assessed. Despite its reported benefits, the overall ß-blocker use was only 60% with nearly a fourfold difference in the use of ß-blockers across National Adult Cardiac Surgery Database sites (20% to 85%), suggesting that this important treatment may be under-used among patients with coronary artery disease. Other investigators have reported the under-use of ß-blockade among patients with coronary artery disease (12). Increasing the use of ß-blockers in eligible patients may be an appropriate target for quality improvement.

There are conflicting reports in the literature about the importance of increased heart rate before CPB with respect to myocardial ischemia and mortality. Reich et al. (3) observed an association between mean pre-CPB tachycardia (>100 bpm) and in-hospital mortality at one of the two reporting sites. However, after multivariate adjustment, pre-CPB heart rate had no independent effect upon mortality. One reason for this finding may be that heart rates >100 bpm are unusual. We observed that only 1.4% (n = 85) of the patients in the current study had preinduction heart rates faster than 100 bpm. The prevalence of heart rates >100 bpm is not reported in the Reich et al. study, but if this was an uncommon event, then finding significance might require a larger sample size. Of note, these authors did observe that heart rate faster than 120 bpm in the post-CPB period was a predictor of mortality (odds ratio = 3.1; Ptrend = 0.001). In an Italian multicenter observational study (13) of 984 patients undergoing CABG, a heart rate >130 bpm at the induction of anesthesia was found to be a univariate predictor of early postoperative mortality. Multivariate analysis was not described in this study. Another study reported no association of operating room heart rate and mortality. Higgins et al. (14) observed 4918 consecutive patients at the Cleveland Clinic during 1993–1995. Among patients with a heart rate faster than 100 bpm, they observed a significant univariate association with mortality (odds ratio = 7.05; Ptrend = 0.0001). This association was not significant in their multivariate model.

In conclusion, we observed a significant association between increased heart rate before the induction of anesthesia and in-hospital mortality that is not explained by differences in patient characteristics. This association has four possible etiologies or may represent any combination of these. Faster heart rate may be the cause of the excess observed mortality. Alternatively, a preinduction heart rate of >=80 bpm could be a marker for existing myocardial damage and left ventricular dysfunction. Increased heart rate might also represent a subset of patients with limited reserve and therefore at increased risk for injury from CPB and cardioplegia. Finally, a faster heart rate may identify a subset of patients in whom ß-blockade is absent, inadequate, or is being withdrawn inappropriately. Because the use of preoperative ß-blockade in CABG patients is associated with improved in-hospital survival, further investigation concerning the effect of intraoperative treatment of increased heart rate with ß-adrenergic blockers on mortality after CABG is warranted.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Royster R, Zvara D. Anti-ischemic drug therapy. In: Kaplan J, Reich D, Konstadt S, eds. Cardiac anesthesia. Philadelphia: WB Saunders, 1999: 95–130.
  2. Slogoff S, Keats AS. Does chronic treatment with calcium entry blocking drugs reduce perioperative myocardial ischemia? Anesthesiology 1988; 68: 676–80.[Web of Science][Medline]
  3. Reich DL, Bodian CA, Krol M, et al. Intraoperative hemodynamic predictors of mortality, stroke, and myocardial infarction after coronary artery bypass surgery. Anesth Analg 1999; 89: 814–22.[Abstract/Free Full Text]
  4. Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 1996; 335: 1713–20.[Abstract/Free Full Text]
  5. Weightman WM, Gibbs NM, Sheminant MR, et al. Drug therapy before coronary artery surgery: nitrates are independent predictors of mortality and ß-adrenergic blockers predict survival. Anesth Analg 1999; 88: 286–91.[Abstract/Free Full Text]
  6. Ferguson TB, Coombs LP, Petersen ED. Preoperative ß-blocker use and mortality and morbidity following CABG surgery in North America. JAMA 2002; 287: 2221–7.[Abstract/Free Full Text]
  7. Gersh B, Braunwald E, Rutherford J. Chronic coronary artery disease. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. Philadelphia: WB Saunders, 1997: 1289–365.
  8. Urban MK, Gordon MA, Harris SN, et al. Intraoperative hemodynamic changes are not good indicators of myocardial ischemia. Anesth Analg 1993; 76: 942–9.[Abstract/Free Full Text]
  9. Cuzick J. A Wilcoxon-type test for trend. Stat Med 1985; 4: 87–90.[Web of Science][Medline]
  10. StataCorp. Stata statistical software. College Station, Texas: Stata Corporation, 1997.
  11. Hjalmarson A, Goldstein S, Fagerberg B, et al. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the metoprolol Cr/Xl randomized intervention trial in congestive heart failure (Merit-Hf). Merit-Hf Study Group. JAMA 2000; 283: 1295–302.[Abstract/Free Full Text]
  12. Rogers WJ, Bowlby LJ, Chandra NC, et al. Treatment of myocardial infarction in the United States (1990 to 1993): observations from the National Registry of Myocardial Infarction. Circulation 1994; 90: 2103–14.[Abstract/Free Full Text]
  13. Puddu PE, Monti F, Brancaccio GL, et al. Univariate analysis of potential risk factors for early mortality (within 28 days) after aortocoronary bypass in Italy. Op-Risk Study Group. Cardiologia 1997; 42: 957–69.[Medline]
  14. Higgins TL, Estafanous FG, Loop FD, et al. ICU admission score for predicting morbidity and mortality risk after coronary artery bypass grafting. Ann Thorac Surg 1997; 64: 1050–8.[Abstract/Free Full Text]
Accepted for publication August 13, 2002.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2002 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press