CT Angiography Before Non-cardiac Surgery?
CT Angiography Before Non-cardiac Surgery?
This was a prospective observational study. We have published details of the study objectives, design, and methods elsewhere.
Patients were eligible if they fulfilled the following criteria: age ≥45; undergoing elective vascular, orthopedic, thoracic, or abdominal surgery in hospital; had sufficient time to undergo coronary computed tomographic angiography before surgery; and had a history of, or risk factors for, atherosclerotic disease or a history of congestive heart failure.
Patients fulfilling any of the following criteria were excluded: planned invasive coronary angiography for preoperative investigation before surgery; history of coronary artery stent implantation; creatinine clearance <35 mL/min; known contrast reaction; current pregnancy; persistent atrial fibrillation or frequent premature beats; heart rate ≥70 beats/min (at centers with single source scanners) or ≥90 beats/min (at centers with dual source scanners), despite drugs to control heart rate just before scheduled coronary computed tomographic angiography; weight >300 lb (136 kg); more than four non-evaluable segments on coronary computed tomographic angiography (non-diagnostic scan); did not undergo non-cardiac surgery within six months after coronary computed tomographic angiography; surgery that did not require at least an overnight stay in hospital; or results of coronary computed tomographic angiography were unblinded because of suspected left main stenosis and patient underwent preoperative coronary revascularization.
The protocol we used for coronary computed tomographic angiography imaging is reported in appendix 1. A panel of expert evaluators (that is, a cardiologist or radiologist with level 3 training in interpretation of coronary computed tomographic angiography) read each angiogram using a 17 segment model of the coronary arteries without knowledge of the clinical data. Each of scans was scored as normal—no evidence of coronary atherosclerosis; non-obstructive coronary artery disease—evidence of at least one coronary artery plaque with a <50% stenosis; obstructive coronary artery disease—at least one coronary artery plaque with a ≥50% stenosis; or extensive obstructive disease—≥50% stenosis in two coronary arteries including the proximal left anterior descending artery, ≥50% stenosis in three coronary arteries, or ≥50% stenosis in the left main coronary artery.
Patients who had previously undergone coronary artery bypass grafting surgery were assessed for the number of unprotected coronary territories (bypass graft with ≥50% stenosis and native coronary artery with ≥50%). Patients with no or one unprotected coronary territory were classified as having obstructive coronary artery disease, and patients with two or three unprotected coronary territories were classified as having extensive obstructive disease.
Patients with a ≥50% stenosis in the left main artery had the results of their coronary computed tomographic angiography reported immediately to their attending physicians. Potentially important incidental non-cardiac findings were disclosed immediately after the scan was interpreted. All other patients had their results withheld from the attending clinical care team until 30 days after surgery.
Study personnel obtained data on patients' characteristics. All patients had scheduled troponin measurements at six to 12 hours after surgery and on the first, second, and third days after surgery. An electrocardiogram was obtained immediately after an increased troponin measurement was detected.
Study personnel followed patients throughout their hospital stay and reviewed their medical records ensuring study orders were followed and noting any outcomes (such as mortality). We contacted patients by phone 30 days after surgery. If patients or their next of kin indicated that they had experienced an outcome (that is, myocardial infarction or mortality) or had been admitted to hospital, study personnel obtained the appropriate documentation from the attending clinicians.
Our primary outcome was a composite of cardiovascular death and non-fatal myocardial infarction within 30 days after surgery. For the diagnosis of myocardial infarction we used the criteria of the universal definition of myocardial infarction that required a typical rise of troponin concentration associated with one of the following: ischemic signs or symptoms, ischemic changes on electrocardiography, or new imaging abnormalities suggestive of myocardial infarction. A panel of clinicians who were blinded to the results of coronary computed tomographic angiography adjudicated the outcomes of cardiovascular death and myocardial infarction. We used the adjudicated results for all statistical analyses.
We did not involve patients or lay people in the design of the study, selection of outcome measures, or recruitment plans and do not plan to disseminate the results to the study participants.
A priori, we determined that we needed 1000 patients to ensure a stable model if our primary event rate was 6%. After we had 30 day outcomes for 950 patients, we determined that our event rate was >7.5% and that we had enough patients to assess whether coronary computed tomographic angiography provided independent prognostic information beyond clinical variables. We therefore stopped recruitment without knowledge of the relation between the findings and the primary outcome and subsequently undertook the analyses. The data monitoring committee reviewed the data when about 40% of the data and separately when 65% of the data on 30 day outcomes were available.
The operations committee prespecified the data analysis plan. Patients who did not complete 30 day follow-up were censored on the last day that their vital status was known. We determined the percentage of patients who had a primary outcome event within 30 days after surgery.
We undertook Cox proportional hazards modeling in which the dependent variable was cardiovascular death and non-fatal myocardial infarction. In the first model, the independent variable was the score on the revised cardiac index. This risk score is well validated, widely used, and recommended for clinical risk stratification in recent guidelines. The model includes six variables: high risk surgery, history of coronary artery disease, history of heart failure, history of cerebrovascular disease, preoperative treatment with insulin, and preoperative creatinine >170 mmol/L. The presence of each variable adds one point, and patients obtain scores from 0–6, with higher scores indicating greater risk.
In the second model, the independent variable was findings on coronary computed tomographic angiography (that is, non-obstructive, obstructive, and extensive obstructive with a reference category of normal coronary arteries). The final model included both the clinical risk scores on the revised cardiac risk index and findings of coronary computed tomographic angiography as independent variables
For all independent predictors of the primary outcome, we determined the adjusted hazard ratio and the associated 95% confidence intervals. A two sided P value was designated a priori as significant at an α of 0.05. Discrimination was assessed through evaluation of the C index. Likelihood ratios were determined for each category of findings on coronary computed tomographic angiography.
We performed post hoc sensitivity analyses to determine if the results were influenced by whether or not a patient had a history of prior vascular disease, had prior coronary artery disease, or had undergone vascular or orthopedic surgery. For these analyses, we used an interaction term in our models for each of these factors. We also undertook another post hoc subgroup analysis restricted to patients without a history of a prior coronary artery bypass grafting.
We calculated reclassification of risk among patients who experienced the primary outcome and separately among patients who did not experience the primary outcome to determine if findings on coronary computed tomographic angiography improved risk classification beyond that achieved with the revised cardiac risk index clinical model. In this analysis, we classified the 30 day primary outcome as low risk <5%, intermediate risk 5–15%, and high risk >15%. We also performed a sensitivity analysis for the net improvement in reclassification that included four risk categories (<5%, 5–10%, ≥10–15%, and ≥15%) and a post hoc evaluation of the risk categories recommended in the European Society of Cardiology guidelines (<1%, 1–5%, and >5%).
We performed post hoc analyses to evaluate the prognostic capabilities of coronary computed tomographic angiography using a ≥70% stenosis threshold to define obstructive coronary artery and extensive obstructive. We also performed post hoc analyses to evaluate the prognostic capabilities of coronary computed tomographic angiography in patients with one or two of the following: history of coronary artery disease, age >70, and diabetes requiring treatment. All analyses were performed with SAS version 9.2 (SAS Institute, Cary, NC).
Methods
Study Design and Eligibility Criteria
This was a prospective observational study. We have published details of the study objectives, design, and methods elsewhere.
Patients were eligible if they fulfilled the following criteria: age ≥45; undergoing elective vascular, orthopedic, thoracic, or abdominal surgery in hospital; had sufficient time to undergo coronary computed tomographic angiography before surgery; and had a history of, or risk factors for, atherosclerotic disease or a history of congestive heart failure.
Patients fulfilling any of the following criteria were excluded: planned invasive coronary angiography for preoperative investigation before surgery; history of coronary artery stent implantation; creatinine clearance <35 mL/min; known contrast reaction; current pregnancy; persistent atrial fibrillation or frequent premature beats; heart rate ≥70 beats/min (at centers with single source scanners) or ≥90 beats/min (at centers with dual source scanners), despite drugs to control heart rate just before scheduled coronary computed tomographic angiography; weight >300 lb (136 kg); more than four non-evaluable segments on coronary computed tomographic angiography (non-diagnostic scan); did not undergo non-cardiac surgery within six months after coronary computed tomographic angiography; surgery that did not require at least an overnight stay in hospital; or results of coronary computed tomographic angiography were unblinded because of suspected left main stenosis and patient underwent preoperative coronary revascularization.
Coronary Computed Tomographic Angiography
The protocol we used for coronary computed tomographic angiography imaging is reported in appendix 1. A panel of expert evaluators (that is, a cardiologist or radiologist with level 3 training in interpretation of coronary computed tomographic angiography) read each angiogram using a 17 segment model of the coronary arteries without knowledge of the clinical data. Each of scans was scored as normal—no evidence of coronary atherosclerosis; non-obstructive coronary artery disease—evidence of at least one coronary artery plaque with a <50% stenosis; obstructive coronary artery disease—at least one coronary artery plaque with a ≥50% stenosis; or extensive obstructive disease—≥50% stenosis in two coronary arteries including the proximal left anterior descending artery, ≥50% stenosis in three coronary arteries, or ≥50% stenosis in the left main coronary artery.
Patients who had previously undergone coronary artery bypass grafting surgery were assessed for the number of unprotected coronary territories (bypass graft with ≥50% stenosis and native coronary artery with ≥50%). Patients with no or one unprotected coronary territory were classified as having obstructive coronary artery disease, and patients with two or three unprotected coronary territories were classified as having extensive obstructive disease.
Patients with a ≥50% stenosis in the left main artery had the results of their coronary computed tomographic angiography reported immediately to their attending physicians. Potentially important incidental non-cardiac findings were disclosed immediately after the scan was interpreted. All other patients had their results withheld from the attending clinical care team until 30 days after surgery.
Study Procedures
Study personnel obtained data on patients' characteristics. All patients had scheduled troponin measurements at six to 12 hours after surgery and on the first, second, and third days after surgery. An electrocardiogram was obtained immediately after an increased troponin measurement was detected.
Study personnel followed patients throughout their hospital stay and reviewed their medical records ensuring study orders were followed and noting any outcomes (such as mortality). We contacted patients by phone 30 days after surgery. If patients or their next of kin indicated that they had experienced an outcome (that is, myocardial infarction or mortality) or had been admitted to hospital, study personnel obtained the appropriate documentation from the attending clinicians.
Outcomes Measures and Definitions
Our primary outcome was a composite of cardiovascular death and non-fatal myocardial infarction within 30 days after surgery. For the diagnosis of myocardial infarction we used the criteria of the universal definition of myocardial infarction that required a typical rise of troponin concentration associated with one of the following: ischemic signs or symptoms, ischemic changes on electrocardiography, or new imaging abnormalities suggestive of myocardial infarction. A panel of clinicians who were blinded to the results of coronary computed tomographic angiography adjudicated the outcomes of cardiovascular death and myocardial infarction. We used the adjudicated results for all statistical analyses.
Patient Involvement
We did not involve patients or lay people in the design of the study, selection of outcome measures, or recruitment plans and do not plan to disseminate the results to the study participants.
Statistical Analyses
A priori, we determined that we needed 1000 patients to ensure a stable model if our primary event rate was 6%. After we had 30 day outcomes for 950 patients, we determined that our event rate was >7.5% and that we had enough patients to assess whether coronary computed tomographic angiography provided independent prognostic information beyond clinical variables. We therefore stopped recruitment without knowledge of the relation between the findings and the primary outcome and subsequently undertook the analyses. The data monitoring committee reviewed the data when about 40% of the data and separately when 65% of the data on 30 day outcomes were available.
The operations committee prespecified the data analysis plan. Patients who did not complete 30 day follow-up were censored on the last day that their vital status was known. We determined the percentage of patients who had a primary outcome event within 30 days after surgery.
We undertook Cox proportional hazards modeling in which the dependent variable was cardiovascular death and non-fatal myocardial infarction. In the first model, the independent variable was the score on the revised cardiac index. This risk score is well validated, widely used, and recommended for clinical risk stratification in recent guidelines. The model includes six variables: high risk surgery, history of coronary artery disease, history of heart failure, history of cerebrovascular disease, preoperative treatment with insulin, and preoperative creatinine >170 mmol/L. The presence of each variable adds one point, and patients obtain scores from 0–6, with higher scores indicating greater risk.
In the second model, the independent variable was findings on coronary computed tomographic angiography (that is, non-obstructive, obstructive, and extensive obstructive with a reference category of normal coronary arteries). The final model included both the clinical risk scores on the revised cardiac risk index and findings of coronary computed tomographic angiography as independent variables
For all independent predictors of the primary outcome, we determined the adjusted hazard ratio and the associated 95% confidence intervals. A two sided P value was designated a priori as significant at an α of 0.05. Discrimination was assessed through evaluation of the C index. Likelihood ratios were determined for each category of findings on coronary computed tomographic angiography.
We performed post hoc sensitivity analyses to determine if the results were influenced by whether or not a patient had a history of prior vascular disease, had prior coronary artery disease, or had undergone vascular or orthopedic surgery. For these analyses, we used an interaction term in our models for each of these factors. We also undertook another post hoc subgroup analysis restricted to patients without a history of a prior coronary artery bypass grafting.
We calculated reclassification of risk among patients who experienced the primary outcome and separately among patients who did not experience the primary outcome to determine if findings on coronary computed tomographic angiography improved risk classification beyond that achieved with the revised cardiac risk index clinical model. In this analysis, we classified the 30 day primary outcome as low risk <5%, intermediate risk 5–15%, and high risk >15%. We also performed a sensitivity analysis for the net improvement in reclassification that included four risk categories (<5%, 5–10%, ≥10–15%, and ≥15%) and a post hoc evaluation of the risk categories recommended in the European Society of Cardiology guidelines (<1%, 1–5%, and >5%).
We performed post hoc analyses to evaluate the prognostic capabilities of coronary computed tomographic angiography using a ≥70% stenosis threshold to define obstructive coronary artery and extensive obstructive. We also performed post hoc analyses to evaluate the prognostic capabilities of coronary computed tomographic angiography in patients with one or two of the following: history of coronary artery disease, age >70, and diabetes requiring treatment. All analyses were performed with SAS version 9.2 (SAS Institute, Cary, NC).
