Satisfactory results are achieved by elective coronary artery bypass grafting (CABG), but the results of emergency CABG are less than satisfactory and readmission for cardiac events is common. We examined long-term results of emergency CABG for unstable angina pectoris from the viewpoints of preoperative, intraoperative, and postoperative factors. Subjects were 154 patients who underwent emergency CABG for unstable angina pectoris. Operative mortality rate was 1.9%. Univariate analysis showed female gender, chronic renal failure, hemodialysis, nonuse of human atrial natriuretic peptide (hANP), nonuse of angiotensin II receptor blockers and aldosterone blockers, 3-month postoperative brain natriuretic peptide level ≥200 pg/ml, and 3-month postoperative aldosterone level ≥100 pg/ml as risk factors for late cardiac events. Multivariate analysis confirmed nonuse of hANP, nonuse of aldosterone blockers, 3-month brain natriuretic peptide level ≥200 pg/ml, and 3-month aldosterone level ≥100 pg/ml as risk factors. Intraoperative hANP infusion and postoperative treatment with aldosterone blockers and angiotensin II receptor blockers can control the renin-angiotensin-aldosterone system, inhibit left ventricular remodeling, decrease extent of infarction, and improve cardiac function, yielding a favorable long-term prognosis. The best results are obtained by combining good surgical technique and perioperative management with the long-term outcome in mind.
Compared to elective coronary artery bypass grafting (CABG), reported mortality rates after CABG in patients with acute coronary syndrome are high at 1.1% to 8.6%. In acute coronary syndrome, the mortality rate for acute myocardial infarction is high at 14.3% to 42.6%, whereas that for unstable angina pectoris is 1.1% to 4.1%, which is relatively low. However, although mortality is low, many patients show delayed cardiac events and cardiac deaths. In patients with unsuccessful percutaneous coronary intervention or impaired left ventricular function due to severe myocardial ischemia, CABG is often indicated rather than medical therapy or repeat percutaneous coronary intervention. Long-term outcome of CABG is influenced by preoperative factors and surgical procedure and by intraoperative factors, postoperative factors, and pharmacotherapy after discharge. Most published studies of emergency CABG provide only short-term results, and reports of long-term outcome are rare. Therefore, we examined the long-term outcome of emergency CABG for unstable angina pectoris in the present study.
Methods
Two hundred thirty patients underwent emergency CABG for acute coronary syndrome at Nihon University Itabashi Hospital (Tokyo, Japan) from June 1, 1998 to May 31, 2008. A retrospective study on unstable angina pectoris was performed in 154 of these 230 consecutive patients after exclusion of patients with acute myocardial infarction. Indications for surgery were ischemia of the left anterior descending coronary arterial territory within 24 hours of onset. All procedures were performed under cardiopulmonary bypass. In general, a left internal thoracic artery graft was used for the left anterior descending coronary artery (but not if the left internal thoracic artery was unsuitable for harvesting, e.g., due to unstable hemodynamics), and a radial artery and/or long saphenous vein graft was used for other sites. Indications for emergency CABG were decided according to Japanese Circulation Society guidelines ( http://www.j-circ.or.jp/guideline/pdf/JCS2007_yamaguchi_h.pdf ) and were (1) lesions of the main trunk of the left coronary artery or left main equivalent disease (severe stenosis of proximal left anterior descending coronary artery and proximal left circumflex coronary artery); (2) persistent angina or myocardial ischemia for which nonsurgical treatment was ineffective; or (3) persistent angina for which percutaneous coronary intervention had been unsuccessful with a risk of extensive myocardial infarction or hemodynamic instability despite use of an intra-aortic balloon pump or percutaneous cardiopulmonary support. Treatment plans were devised in consultation with cardiologists.
Preoperative factors examined were age ≥80 years, gender, shock, lesions of the main trunk of the left coronary artery, ejection fraction <40%, intra-aortic balloon pump, venoarterial bypass, diabetes mellitus, hypertension, hyperlipidemia, obesity, smoking, chronic renal failure, hemodialysis, cerebrovascular disease, a European System for Cardiac Operative Risk Evaluation score ≥10 points, brain natriuretic peptide (BNP) level ≥200 pg/ml, and aldosterone level ≥100 pg/ml. Intraoperative factors examined were extracorporeal circulation time ≥120 minutes, nonuse of left internal thoracic artery, and intraoperative commencement of human atrial natriuretic peptide (hANP) therapy. Postoperative factors investigated were postoperative administration of angiotensin II receptor blockers (ARBs), aldosterone blockers, angiotensin-converting enzyme inhibitors, β blockers, calcium antagonists, and statins, 3-month postoperative BNP level ≥200 pg/ml, and 3-month postoperative aldosterone level ≥100 pg/ml. We measured BNP and aldosterone levels immediately before surgery and 3 months postoperatively. We examined late cardiac events (defined as heart failure, arrhythmia, or ischemic heart disease requiring treatment) in patients who were discharged from hospital after surgery. This was a retrospective study with a 100% follow-up rate, and a mean follow-up period of 3.83 years (0 to 10). Approval for this study was received from the ethics committee of Nihon University Itabashi Hospital. Details of the study were explained to each patient and/or patient’s family and informed consent was obtained.
All patients were administered aspirin (81 to 100 mg/day) and isosorbide dinitrate (40 mg/day) postoperatively. A calcium antagonist was administered to patients who had undergone radial arterial grafting, to prevent vasospasm. Treatment with ARB, angiotensin-converting enzyme inhibitors, β blocker, and aldosterone blockers was given at the discretion of the attending physician.
Results are presented as mean ± SD. For statistical analysis, univariate logistical regression analysis of preoperative, intraoperative, and postoperative factors was performed. Variables showing significance were then subjected to multivariate analysis. Overall mortality rate, cardiovascular mortality rate, and postoperative cardiovascular event-free rate were determined by the Kaplan-Meier method. Student’s t test and Fisher’s exact test were used for other statistical analyses. A p value <0.05 was considered to indicate statistical significance.
Results
Preoperative background factors of the 154 patients are listed in Table 1 . Of these, 15 patients (9.7%) were ≥80 years of age. Three patients (1.9%) were in shock, with 3 (1.9%) requiring support by venoarterial bypass. One hundred one patients (65.6%) were supported by intra-aortic balloon pumping. There were 9 patients (5.8%) on hemodialysis, 13 (8.4%) with left ventricular dysfunction, and 33 (21.4%) with a European System for Cardiac Operative Risk Evaluation score ≥10 points. Preoperative BNP level was >200 pg/ml in 29 patients (18.8%), and preoperative aldosterone level was >100 pg/ml in 20 patients (13.0%; Table 1 ).
| Characteristic | |
| Age (years) | 66.8 ± 10.1 (41–91) |
| ≥80 years | 15 (10%) |
| Men:women | 116:38 |
| Body surface area (m 2 ) | 1.63 ± 0.18 (1.22–2.19) |
| Preoperative factors | |
| Shock | 3 (2%) |
| Left main trunk disease | 98 (64%) |
| EuroSCORE (points) | 7.5 ± 2.9 (2–16) |
| EuroSCORE ≥10 points | 33 (21%) |
| Diabetes mellitus | 70 (46%) |
| Hypertension | 116 (75%) |
| Hyperlipidemia | 95 (62%) |
| Obesity | 35 (23%) |
| Smoking | 52 (34%) |
| Chronic renal failure | 22 (14%) |
| Cerebral infarction | 9 (6%) |
| Hemodialysis | 9 (6%) |
| Ejection fraction | 57.0 ± 13.2 (20–83) |
| Ejection fraction <40% | 13 (8%) |
| Intra-aortic balloon pump | 101 (66%) |
| Venoarterial bypass | 3 (2%) |
| Preoperative investigations | |
| Brain natriuretic peptide ≥200 pg/ml | 29 (19%) |
| Brain natriuretic peptide (pg/ml) | 178.5 ± 263.6 (13.3–1,410) |
| Aldosterone ≥100 pg/ml | 20 (13%) |
| Aldosterone (pg/ml) | 62.9 ± 53.5 (6.0–199) |
Intraoperative and postoperative factors are presented in Table 2 . A left internal thoracic artery graft was used in 135 patients (87.7%), and extracorporeal circulation time exceeded 120 minutes in 57 (37.0%). Intraoperatively, hANP was administered to 73 patients (47.4%), and aspirin was given to all patients postoperatively and isosorbide nitrate was administered to 126 (81.8%). ARB was administered to 61 patients (39.6%), angiotensin-converting enzyme inhibitors to 18 (11.7%), β blockers to 25 (16.2%), aldosterone blockers to 67 (43.5%), calcium antagonists to 106 (68.8%), and statins to 71 (46.1%). The 3-month postoperative BNP level was >200 pg/ml in 21 patients (13.6%), and 3-month postoperative aldosterone level was >100 pg/ml in 18 patients (11.7%; Table 2 ).
| Intraoperative factors | |
| Left internal thoracic artery graft | 135 (88%) |
| Aortic cross clamping time (minutes) | 48.8 ± 28.6 (0–112) |
| Extracorporeal circulation time (minutes) | 112.2 ± 35.2 (45–182) |
| Extracorporeal circulation time ≥120 minute | 57 (37%) |
| Human atrial natriuretic peptide infusion | 73 (47%) |
| Postoperative factors | |
| Aspirin | 215 (100%) |
| Isosorbide dinitrate | 126 (82%) |
| Angiotensin II receptor blocker | 61 (40%) |
| Angiotensin-converting enzyme inhibitor | 18 (12%) |
| β blockers | 25 (16%) |
| Aldosterone blockers | 67 (44%) |
| Calcium antagonists | 106 (69%) |
| Statins | 71 (46%) |
| Brain natriuretic peptide (3 months, pg/ml) | 133.3 ± 201.9 (11–1,060) |
| Brain natriuretic peptide (3 months) ≥200 pg/ml | 21 (14%) |
| Aldosterone (3 months, pg/ml) | 71.6 ± 38.3 (12–300) |
| Aldosterone (3 months) ≥100 pg/ml | 18 (12%) |
Operative mortality rate was 1.9% (n = 3). Cause of death was heart failure in 2 patients and pneumonia in 1. There were 14 late deaths, with the cause being heart failure in 8 cases, pneumonia in 3 cases, and cerebral infarction, acute renal failure, and malignancy in 1 case each. Postoperative 1-year survival rate was 93.5%, 5-year survival rate was 89.2%, and 10-year survival rate was 84.1% ( Figure 1 ). Postoperative 1-year survival rate for cardiac death (excluding noncardiac causes of death) was 96.0%, 5-year survival rate was 91.5%, and 10-year survival rate was 91.5% ( Figure 1 ).
Late cardiac events were reported in 16 patients, including 13 cases of heart failure, 2 cases of ischemic heart disease, and 1 case of arrhythmia. Average time of onset was 748.9 days (115 to 2,195) after discharge from hospital, with 3 events (23.1%) occurring within 6 months of discharge and 5 events (38.5%) occurring within 1 year. Postoperative cardiac event-free rates were 97.2% at 1 year, 87.1% at 5 years, and 87.1% at 10 years ( Figure 1 ).
Univariate analysis of early deaths revealed the following risk factors. Early deaths occurred in only 3 patients. No risk factors were found among preoperative, intraoperative, or postoperative factors. Dialysis or history of cardiovascular disease showed no statistical significance, but the p value was 0.0864, and these might become risk factors if the number of patients is increased ( Table 3 ). Univariate analysis of late cardiac events revealed the following risk factors: female gender, chronic renal failure, hemodialysis, intraoperative nonuse of hANP, postoperative nonuse of ARB and aldosterone blockers, 3-month postoperative BNP level ≥200 pg/ml, and 3-month postoperative aldosterone level ≥100 pg/ml. Multivariate analysis of late cardiac events confirmed intraoperative nonuse of hANP, nonuse of aldosterone blockers, 3-month postoperative BNP level ≥200 pg/ml, and 3-month postoperative aldosterone level ≥100 pg/ml as risk factors ( Table 4 ).
| p Value | |
|---|---|
| Preoperative factors | |
| Age ≥80 years | 0.9824 |
| Female gender | 0.7273 |
| EuroSCORE ≥10 points | 0.9760 |
| Diabetes mellitus | 0.6735 |
| Hypertension | 0.7273 |
| Hyperlipidemia | 0.9687 |
| Obesity | 0.6617 |
| Smoking | 0.9872 |
| Cerebrovascular disease | 0.0864 |
| Chronic renal failure | 0.3649 |
| Hemodialysis | 0.0864 |
| Left main trunk disease | 0.9123 |
| Shock | 0.9857 |
| Intra-aortic balloon pump | 0.2692 |
| Venoarterial bypass | 0.9825 |
| Ejection fraction <40% | 0.1637 |
| Brain natriuretic peptide ≥200 pg/dl | 0.5266 |
| Aldosterone ≥100 pg/dl | 0.9796 |
| Intraoperative factors | |
| Left internal thoracic artery not used | 0.9802 |
| Extracorporeal circulation time ≥120 minutes | 0.9767 |
| Human atrial natriuretic peptide not used | 0.6270 |
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