Existing Non-Gated CT Coronary Calcium Predicts Operative Risk in Patients Undergoing Non-Cardiac Surgeries (ENCORES)

Abstract

Background:

Preoperative cardiovascular risk stratification prior to non-cardiac surgery is a common clinical challenge. Coronary artery calcium scores from ECG-gated chest computed tomography (CT) imaging are associated with perioperative events. At the time of preoperative evaluation, many patients will not have had ECG-gated CT imaging, but will have had non-gated chest CT studies performed for a variety of non-cardiac indications. We evaluated relationships between coronary calcium severity estimated from prior non-gated chest CT imaging and perioperative major clinical events (MCE) after non-cardiac surgery.

Methods:

We retrospectively identified consecutive adults age ≥45 years who underwent in-hospital, major non-cardiac surgery from 2016 to 2020 at a large academic health system comprising four acute care centers. All patients had non-gated (contrast or non-contrast) chest CT imaging performed within one year prior to surgery. Coronary calcium in each vessel was retrospectively graded from absent to severe using a 0-3 scale (absent, mild, moderate, severe) by physicians blinded to clinical data. The estimated coronary calcium burden (ECCB) was computed as the sum of scores for each coronary artery (0 to 9 scale). A Revised Cardiac Risk Index (RCRI) was calculated for each patient. Perioperative MCE was defined as all-cause death or myocardial infarction within 30 days of surgery.

Results:

A total of 2,554 patients (median age 68 years, 49.7% women, median RCRI 1) were included. The median time interval from non-gated chest CT imaging to non-cardiac surgery was 15 days (IQR 3-106 days). The median ECCB was 1 (IQR 0-3). Perioperative MCE occurred in 136 (5.2%) patients. Higher ECCB values were associated with stepwise increases in perioperative MCE (0: 2.9%, 1-2: 3.7%, 3-5: 8.0%; 6-9: 12.6%, p<0.001). Addition of ECCB to a model with the RCRI improved the C-statistic for MCE (from 0.675 to 0.712, p=0.018), with a net reclassification improvement of 0.428 (95% CI 0.254-0.601, p<0.0001). An ECCB ≥3 was associated with two-fold higher adjusted odds of MCE versus an ECCB <3 (aOR 2.11, 95% CI 1.42-3.12).

Conclusions:

Prevalence and severity of coronary calcium obtained from existing non-gated chest CT imaging improves preoperative clinical risk stratification prior to non-cardiac surgery.

BACKGROUND

Major adverse cardiovascular events account for significant perioperative morbidity and mortality, occurring in 1 of every 33 hospitalizations for major non-cardiac surgery.¹ Preoperative cardiovascular risk stratification prior to non-cardiac surgery is a common clinical challenge and risk discrimination remains suboptimal, particularly for patients with poor or unknown functional status.^2,3 Thus, novel approaches to perioperative risk prediction are needed.

Coronary artery calcium (CAC) imaged by electrocardiographic (ECG)-gated, non-contrast, chest computed tomography (CT) is an independent predictor of overall long-term cardiovascular events in multiple large cohort studies.^4-7 CAC scores measured from ECG-gated CT scans prior to non-cardiac surgery have also been shown to independently predict perioperative cardiovascular events.^8-11 However, the impact of this observation has been limited, since at the time of preoperative evaluation, results of a CT coronary angiography or ECG-gated CAC score are not commonly available.

Conveniently, many surgical candidates will have had non-ECG gated chest CT imaging already performed for a variety of non-cardiac indications, within the prior 12 months. Repurposing these non-gated chest CT studies might provide a cost-effective and efficient approach to risk discrimination during preoperative assessment. To our knowledge, no prior studies have examined the utility of coronary calcium measurements from non-gated CT chest imaging to improve perioperative risk stratification. Therefore, we investigated associations between coronary calcium estimates from existing non-gated chest CT imaging and the incidence of perioperative major clinical events (MCE) in a large cohort of patients undergoing major, non-cardiac surgery.

METHODS

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Study Cohort

We retrospectively identified adults age ≥45 years undergoing in-hospital, non-cardiac, intermediate-to-high risk surgery between January 1, 2016 to September 15, 2020 at NYU Langone Health, a large, urban, academic health system comprising four acute care centers in the New York metropolitan area. Individuals undergoing outpatient surgeries without a planned overnight hospital stay were not included. Patients with a non-gated chest CT (including contrast or non-contrast studies) performed within 1 year prior to the index non-cardiac surgery were eligible for inclusion. Patients were excluded if they had documentation of prior percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Patients were further excluded at the time of CT review if they had imaging evidence of PCI or CABG (not reported on history), prior prosthetic valve replacement or left ventricular assist device, missing CT studies, CT studies with uninterpretable image quality for the purpose of coronary calcium determination, or underwent low risk surgeries (endoscopic, cosmetic, or ophthalmologic procedures). For patients with two or more surgeries during the study period, only the most recent surgery was included in the final analysis. This study was approved by the New York University School of Medicine Institutional Review Board.

Data Collection

Clinical data, including demographics, relevant clinical comorbidities, and type of non-cardiac surgery, were obtained from the electronic health record (Epic Systems, Verona, WI), which is an integrated electronic health record including all inpatient and outpatient visits across the health system. We queried all data in the electronic health record, including data entered during prior inpatient or outpatient visits in encounter diagnoses, problem lists, or medical histories, as previously described.¹² Patients were determined to have established cardiovascular disease if they had a diagnosis of ischemic heart disease, peripheral artery disease, or cerebrovascular disease. The RCRI was determined for each surgical candidate based on a history of ischemic heart disease, heart failure, TIA or stroke, diabetes with preoperative insulin use, preoperative creatinine >2.0, and high-risk surgery, defined as intraperitoneal, intrathoracic, or supra-inguinal vascular surgery.¹³

Computed Tomographic Interpretation

CT studies were retrospectively reviewed for each patient undergoing surgery. If more than one CT chest imaging study was performed within the year prior to surgery, the most recent study was selected for review. All CT chest protocols that did not use ECG-gating were acceptable, including non-contrast CT and contrast-enhanced CT imaging of the chest.

The extent and severity of coronary artery calcium was estimated from non-gated CT chest images. Within each study, if both contrast and non-contrast enhanced images were available, the non-contrast images were preferentially reviewed because intravascular contrast may obscure adjacent coronary calcium in some cases. Window widths and levels were optimized for calcium viewing. When available, 2.0 mm slice thickness reconstructions were used; if unavailable, reconstructions closest to 2.0 mm were used, with priority given to thinner reconstructions.

Each of the three major epicardial coronary vessels and their associated branches was assessed (i.e. left main/left anterior descending artery, left circumflex artery, and right coronary artery), with the left main and left anterior descending coronary artery combined as a single vessel due to the difficulty of visually separating these two vessels on non-gated studies. The calcium severity in each vessel was scored based on the approximate length of calcium visualized, as previously described.¹⁴ These predetermined scoring criteria were: absent (0% calcified), mild (1-24% of the total artery length calcified), moderate (25-49% of the total artery length calcified), or severe (≥50% of the total artery length calcified). Calcium in a branch vessel was added to the total length of calcium of the parent vessel (e.g. the length of calcium in a diagonal branch was added to the length of calcium in the left anterior descending). Grades of calcium were subsequently assigned a corresponding numerical score on an ordinal scale as 0 (absent), 1 (mild), 2 (moderate), or 3 (severe).

An estimated coronary calcium burden (ECCB) was recorded for each patient as the sum of these scores (range: 0-9). Clinically relevant ECCB thresholds (ECCB 0: no calcium, 1-2: includes only mild or moderate coronary calcification, 3-5: may include severe disease in one vessel, and 6-9: may include severe disease in at least two vessels) were selected for subgroup analyses.

To ensure a pragmatic approach, four physicians (DC, DH, SM, ND) without prior formal training in CT interpretation reviewed chest CT imaging to estimate coronary calcium severity. Each physician completed a brief training (approximately 90 minutes in total) that included a video tutorial, written instructions, and case review. All readers were blinded to patient information and surgical outcomes at the time of CT interpretation. To evaluate the inter-reader reliability of coronary calcium assessment from CT imaging, a sample of 100 randomly selected studies (50 contrast studies and 50 non-contrast studies) were independently interpreted by two non-radiologist physician readers, each blinded to the CAC estimation by the other.

Clinical Outcomes

The primary outcome was perioperative MCE, defined as in-hospital myocardial infarction (MI) during the index surgical admission or all-cause death within the first 30 post-operative days. Post-operative diagnoses were identified by relevant International Classification of Diseases 9^th revision (ICD-9) and 10^th revision (ICD-10) diagnosis codes. MI was adjudicated according to the Fourth Universal Definition of Myocardial Infarction and required the presence of a cardiac troponin measurement exceeding the 99^th percentile of the upper reference limit, with documented ischemic symptoms, ECG changes, or new ventricular wall motion abnormalities.¹⁵ MI adjudication was performed blinded to the results of the CT-derived ECCB.

Statistical Analyses

Categorical variables are reported as frequencies and percentages and were compared by Chi-square tests. Continuous variables are shown using mean (SD) and median (interquartile range [IQR]) and were compared using T-tests or non-parametric Mann-Whitney test for non-normally distributed data. The area under the receiver operating characteristic curve (C-statistic) was calculated based on the Harrell method for models with and without the ECCB, and model performance was compared using Delong's test.¹⁶ The discriminative value of the ECCB was further characterized by the continuous net reclassification improvement and the integrated discrimination index, with p-values calculated using the Hosmer-Lemeshow goodness of fit test. Model discrimination was also assessed by the likelihood ratio test. Inter-reader reliability was assessed by percent agreement, Cohen's kappa coefficient, and the intraclass correlation coefficient (ICC). Multivariable logistic-regression models were generated to estimate associations between coronary calcium and perioperative outcomes, adjusted for age, sex, and Revised Cardiac Risk Index (RCRI). Sensitivity analyses were performed in patients without known atherosclerotic disease. Statistical analyses were performed using SPSS 27 (IBM SPSS Statistics, Armonk, NY, USA) and R (Vienna, Austria). Statistical tests are two-sided and p-values <0.05 were considered to be statistically significant.

RESULTS

Study Population

We identified 24,939 in-hospital, intermediate-to-high risk, non-cardiac surgeries, performed on adults age ≥45 years. In 4,190 (16.8%) of these surgical cases, patients had a non-gated chest CT performed within 1 year prior to the index surgery. A total of 2,554 patients (52.0%) met full eligibility criteria and were included in the final analyses (Figure 1).

Figure 1: Patient selection flow diagram.

Baseline characteristics of patients included in the study analyses are described in Table 1. The median age was 68 years, 49.7% were women, and 60.1% were of white race. The median RCRI score was 1. The most common surgical subtypes were general (29.4%), orthopedic (16.8%), neurosurgical (13.9%), thoracic (13.4%), and vascular (12.4%) surgery. High-risk surgeries, defined as intraperitoneal, intrathoracic, or supra-inguinal vascular surgeries, were performed in 23.0% of cases. General anesthesia was used in 82.3% of surgical procedures, with monitored anesthesia care or regional block used in the remaining cases.

Table 1: Patient demographics, medical history, and surgical characteristics.

Patient Characteristics (n=2554)	CT (n=2554)
Age in years, median [IQR]	68 [59-77]
Female sex, n (%)	1270 (49.7%)
Race, n (%)
White	1536 (60.1%)
African American (Black)	274 (10.7%)
Asian	243 (9.5%)
Other race	435 (17.0%)
Native American	8 (0.3%)
Unknown / declined to answer	58 (2.3%)
Body mass index in kg/m2, median [IQR] *	25.6 [22.1-30.2]
Left ventricular ejection fraction, median [IQR] †	65 [57-67]
Baseline comorbidities, n (%)
Hypertension	1192 (46.7%)
Atherosclerotic cardiovascular disease ‡	714 (28.0%)
Ischemic heart disease	317 (12.4%)
Peripheral artery disease	222 (8.7%)
Cerebrovascular disease	349 (13.7%)
Heart failure	369 (14.4%)
Chronic kidney disease with preoperative creatinine >2.0	324 (12.7%)
Diabetes mellitus with preoperative insulin use	550 (21.5%)
Chronic obstructive pulmonary disease	250 (9.8%)
Prior deep venous thrombosis / pulmonary embolism	39 (1.5%)
Medications on admission, n (%)
ACE / ARB §	380 (14.9%)
Beta-blocker	533 (20.9%)
Statin	691 (27.1%)
Aspirin	361 (14.1%)
P2Y12 inhibitor ∥	73 (2.9%)
Direct oral anticoagulant	90 (3.5%)
Warfarin	17 (0.7%)
Preoperative labs, median [IQR]
Hemoglobin (g/dL)	11.9 [10-13.5]
Creatinine (mg/dL)	0.94 [0.74-1.31]
Revised Cardiac Risk Index, median [IQR]	1 [0-2]
Revised Cardiac Risk Index, n (%)
0	1094 (42.8%)
1	793 (31.0%)
2	416 (16.3%)
3+	251 (9.8%)
Surgical Characteristics
Types of surgeries, n (%)
General surgery	750 (29.4%)
Orthopedic surgery	428 (16.8%)
Neurosurgery	356 (13.9%)
Thoracic surgery	343 (13.4%)
Vascular surgery	317 (12.4%)
Urological surgery	166 (6.5%)
Otolaryngology	86 (3.4%)
Plastic surgery	60 (2.3%)
Gynecologic surgery	48 (1.9%)
Other	0 (0%)
Surgery risk, n (%)
High-risk	588 (23.0%)
Intermediate-risk	1966 (77.0%)
Anesthesia type, n (%)
General	2102 (82.3%)
Monitored care	329 (12.9%)
Regional block	123 (4.8%)

^*Body mass index available for 2520 / 2554 patients (98.7%).

^†Left ventricular ejection fraction data were available for 1,467 / 2,554 patients (57.4%).

^‡Defined as established coronary artery disease, myocardial infarction, peripheral artery disease, or cerebrovascular disease prior to non-cardiac surgery.

^§ACE / ARB = angiotensin-converting enzyme inhibitors / angiotensin receptor blockers

^∥P2Y12 inhibitor = clopidogrel, ticagrelor, or prasugrel

CT Interpretation

The median time interval from non-gated chest CT imaging to non-cardiac surgery was 15 days (IQR 3-106 days). CT imaging included 1070 (41.9%) non-contrast and 1484 (58.1%) contrast-enhanced scans (Table 2). Overall, 60.3% of patients had at least mild coronary artery calcification in one or more coronary vessels (Figure 2A), and 22.8% had at least mild calcium involving all three coronary arteries (Table 2). The most commonly calcified coronary vessel was the left anterior descending (in 58.8% of cases), followed by the right coronary artery (32.7%) and left circumflex artery (31.6%). The median ECCB, the sum of semi-quantitative estimates of calcium severity, was 1 (IQR 0-3). The frequency distribution of ECCB is shown in Figure 2B.

Table 2: Computed tomography (CT) imaging characteristics and estimated coronary calcium burden.

Imaging Characteristics
Time from CT to surgery in days, median [IQR]	15 [3-106]
CT characteristics, n (%)
Non-contrast studies reviewed	1070 (41.9%)
Contrast enhanced studies reviewed	1484 (58.1%)
Average CT slice (mm)	1.9 ± 0.7
Coronary Calcium by Vessel
Left anterior descending, n (%)
None	1051 (41.2%)
Mild (0-24% length)	798 (31.2%)
Moderate (25-49% length)	345 (13.5%)
Severe (50-100% length)	360 (14.1%)
Right coronary artery, n (%)
None	1719 (67.3%)
Mild (0-24% length)	521 (20.4%)
Moderate (25-49% length)	127 (5.0%)
Severe (50-100% length)	187 (7.3%)
Left circumflex artery, n (%)
None	1746 (68.4%)
Mild (0-24% length)	548 (21.4%)
Moderate (25-49% length)	132 (5.2%)
Severe (50-100% length)	128 (5.0%)
Extent and Severity of Coronary Calcium
Extent of any coronary calcium, n (%)
0-vessel	1013 (39.7%)
1-vessel	519 (20.3%)
2-vessel	439 (17.2%)
3-vessel	583 (22.8%)
Extent of moderate-to-severe coronary calcium, n (%)
0-vessel	1794 (70.2%)
1-vessel	404 (15.8%)
2-vessel	193 (7.6%)
3-vessel	163 (6.4%)

Figure 2: Distribution of coronary calcium severity and estimated coronary calcium burden.

Pie chart demonstrating the prevalence of coronary calcium by severity (Panel A) and a frequency distribution of the estimated coronary calcium burden (ECCB) (Panel B) are shown. ECCB was calculated for each patient as the sum of ordinal qualitative estimates of coronary calcium (from absent [0] to severe [3]) for all three coronary arteries.

Inter-reader reliability for CT interpretation of the ECCB was excellent overall, with an intraclass correlation coefficient (ICC) of 96% (95% CI 0.94-0.98), and in subgroups by contrast enhancement and when stratified by coronary artery (Table 3).

Table 3: Inter-reader reliability amongst computed tomography (CT) readers.

A sample of 100 CT studies (including 50 contrast-enhanced and 50 non-contrast) were independently interpreted by two readers. Inter-reader reliability for CT interpretation of the estimated coronary calcium burden was excellent overall, with an intraclass correlation coefficient (ICC) of 0.96 (95% CI 0.94-0.98).

Inter-reader reliability	ECCB*: ICC (95% CI)	Any CAC†: Kappa (95% CI)	Moderate-to- Severe CAC: Kappa (95% CI)
Per-patient analysis (n)
All CT studies (100)	0.96 (0.94-0.98)	0.82 (0.70-0.94)	0.85 (0.73-0.96)
Contrast enhanced CT (50)	0.95 (0.91-0.97)	0.74 (0.56-0.93)	0.89 (0.74-1.00)
Non-contrast CT (50)	0.97 (0.95-0.98)	0.90 (0.77-1.00)	0.80 (0.64-0.97)
Stratified by Coronary Artery (n)
Left anterior descending (100)	0.93 (0.90-0.96)	0.91 (0.83-1.00)	0.82 (0.70-0.94)
Left circumflex (100)	0.91 (0.87-0.94)	0.76 (0.62-0.89)	0.76 (0.55-0.96)
Right coronary (100)	0.94 (0.91-0.96)	0.73 (0.60-0.86)	0.83 (0.68-0.99)

^*ECCB = estimated coronary calcium burden

^†CAC = coronary artery calcium

Perioperative Outcomes

The incidence of perioperative death or MI was 5.2%; 56 (2.2%) patients had a perioperative myocardial infarction, and 86 (3.4%) died in-hospital or within 30 days of surgery. Baseline characteristics of patients with and without perioperative MCE are shown in Table S1. Patients with any CAC had a higher risk of perioperative MCE versus those without any detectable CAC (6.8% vs 2.9%, p<0.001) (Figure 3A). Higher MCE was observed with increasing number of vessels with any calcium (no calcium: 2.9%, 1-vessel: 4.2%, 2-vessels: 4.8%, 3-vessels: 10.6%, p<0.001), and the number of vessels with moderate-to-severe calcium (no moderate-to-severe calcium: 3.6%, 1-vessel: 7.2%, 2-vessels: 9.8%, 3-vessel: 13.5%, p<0.001), as shown in Figures 3B and 3C.

Figure 3: Incidence of perioperative MCE stratified by prevalence and severity of CAC.

The incidence of perioperative major clinical events (MCE) increased with any coronary calcium (p<0.001; Panel A), and in a stepwise pattern for increasing number of coronary vessels with any calcium (p<0.001; Panel B), number of coronary vessels with moderate-to-severe calcium (p<0.001, Panel C), and according to the estimated coronary calcium burden (p<0.001; Panel D). Odds ratios for MCE adjusted for age, sex and RCRI are shown.

The ECCB was associated with perioperative outcomes. The incidence of perioperative MCE increased in a stepwise fashion by ECCB (ECCB of 0: 2.9%, ECCB range 1-2: 3.7%, ECCB range 3-5: 8.0%, and ECCB range 6-9: 12.6%, p<0.001) (Figure 3D). As a continuous function, the ECCB was associated with a C-statistic of 0.657 (95% CI 0.608-0.706) for MCE. Addition of ECCB to a model with the RCRI improved the C-statistic for MCE from 0.675 to 0.712 (p=0.018), with a net reclassification improvement of 0.428 (95% CI 0.254-0.601, p<0.0001) an integrated discrimination index of 0.010 (95% CI 0.004-0.017; p=0.0067), and a likelihood ratio test p<0.001. When the ECCB was added to a model including age, sex, and RCRI, there was a trend toward an improvement in the C-statistic from 0.704 to 0.718 (p=0.135), with a net reclassification improvement of 0.312 (95% CI 0.138-0.485, p=0.0043) an integrated discrimination index of 0.006 (95% CI 0.0012-0.0104; p=0.013), and a likelihood ratio test p=0.0012. In analyses adjusted for age, sex, and RCRI, each increase in ECCB was significantly associated with perioperative MCE (adjusted Odds Ratio [aOR] 1.12, 95% CI 1.05-1.21, p<0.001). When ECCB was evaluated as a categorical variable, ECCB 3-5 (aOR 1.82, 95% CI 1.06-3.12) and 6-9 (aOR 2.58, 95% CI 1.43-4.66) were associated with higher adjusted odds of MCE compared to patients without any evidence of coronary calcium (ECCB 0) (Figure 3D). An ECCB of ≥3 was associated with a higher adjusted odds of MCE versus an ECCB <3 (aOR 2.11, 95% CI 1.42-3.12).

Although the ECCB positively correlated with the RCRI (Spearman’s Coefficient (ρ): 0.283, p<0.001), at each RCRI stratification, a wide range of ECCB values were observed (Figure S1A). Among patients with an RCRI of 0, for example, 49.5% had detectable coronary calcium (ECCB ≥1), while 19.5% of patients with RCRI ≥3 had no coronary calcium (ECCB 0). As expected, the incidence of MCE was highest among patients with elevated RCRI. Within each RCRI strata, the incidence of MCE was numerically lower among patients without detectable coronary calcium (ECCB of 0) versus those with ECCB >0 (Figure 4A). Patients with an ECCB of 0-2, indicative of only mild calcium, had a significantly lower risk of MCE across multiple RCRI subgroups compared to patients with higher ECCB ≥3 (Figure 4B). The relationship between RCRI, ECCB thresholds, and the incidence of perioperative MCE is shown in Figure S1B.

Figure 4: Incidence of perioperative MCE stratified by ECCB and RCRI.

Perioperative major clinical events (MCE) in patients with an estimated burden of coronary calcium (ECCB) of 0 versus ≥1 (Panel A) or an ECCB of 0-2 versus ≥3 (Panel B), stratified by the Revised Cardiac Risk Index are shown.

We observed associations between the ECCB and perioperative MCE in subgroups of younger (age <65) and older (age ≥65) adults, with and without established atherosclerotic cardiovascular disease, and in patients with low RCRI <2 or elevated RCRI ≥2 (Figure S2A). In a sensitivity analysis excluding patients with established cardiovascular disease, the incidence of perioperative MCE increased in a stepwise fashion by ECCB (Figure S2B). Findings were also similar in an analysis of the overall cohort including statin use as a covariate in the multivariable model (Figures S3A & S3B). When stratified by age and RCRI (Figures S4 & S5), younger adults (age <65) with an RCRI of 0 and an ECCB of 0 exhibited a low risk of MCE (0.6%, Figure S4A). Among younger adults with a mild ECCB of 0-2, MCE occurred in <6%, irrespective of RCRI score. In contrast, young adults with an ECCB ≥3 and an RCRI >2 had a substantially elevated incidence of MCE (Figure S5A). Older adults (≥65 years) with ECCB ≥3 also had a higher incidence of MCE compared to those with milder coronary calcium (ECCB 0-2), but this was only observed among patients with lower RCRI ≤1 (Figure S5B).

Estimation of coronary calcium from both non-contrast and contrast-enhanced CT studies correlated with perioperative MCE (Figure S2A), with durable associations between the number of calcified coronary vessels (Figures S6A, S6B) and the ECCB (Figures S7A, S7B) and clinical outcomes. However, for contrast-enhanced studies, risk discrimination was poorer in patients with a lower extent and severity of coronary calcium.

DISCUSSION

In a large cohort of patients undergoing major non-cardiac surgery, we identified that coronary calcium derived from non-gated chest CT studies, performed in the year prior to surgery, demonstrated a positive correlation with perioperative outcomes. Stepwise increases in MCE were observed with increasing ECCB. When combined in a model with the RCRI, the ECCB significantly improved risk prediction. Among patients with an RCRI of 0 and absent or very mild coronary calcium, the risk of MCE was low, a finding that was most striking in older adults age ≥65 years. To our knowledge, this is the first study to use preexisting, preoperative non-gated chest CT imaging to evaluate perioperative risks of non-cardiac surgery.

Prior studies demonstrate that CAC from ECG-gated CT imaging prior to non-cardiac surgery is associated with perioperative cardiovascular events.^8-11 In a single center study of 239 patients undergoing preoperative ECG-gated chest CT imaging, patients with CAC scores ≥113 were four-fold more likely to experience 30-day post-operative cardiovascular events than patients with lower scores.⁸ Prior studies also report strong agreement between CAC scores derived from non-ECG gated versus ECG-gated CT imaging,¹⁷ with extensive data reported from low-dose CT imaging from COPD databases and lung cancer screening trials.^18-22 In a cohort of patients undergoing lung cancer screening, the incidental finding of coronary calcification on non-gated CT imaging conferred higher risk for long-term cardiac events.¹⁷ Sheth et al. reported that preoperative ECG-gated coronary CT angiography provided independent and additive prognostic information to the RCRI, although in that study, CT imaging was more likely to lead to inappropriate overestimation of risk.²³ In contrast to prior studies that prospectively evaluated ECG-gated CAC scoring and/or coronary CT angiography, the present analyses demonstrate the value of leveraging existing non-ECG gated CT studies, performed for indications other than cardiovascular risk stratification, with no added cost to the healthcare system. We demonstrate the feasibility and outstanding reproducibility of pragmatic estimates of coronary calcium from existing non-ECG gated imaging and additional associations with short-term surgical outcomes.

The ordinal scale for the ECCB in the present analyses was developed based on prior reports in which increasing ordinal CAC scores from low-dose chest CT imaging correlated with cardiovascular death.^14,24,25 Although we estimated the degree of severity of calcium in each vessel based on the length of calcium visualized as previously described,¹⁴ the current scoring differs from the prior literature by lowering the threshold of severity across all levels: for mild calcium, the threshold was lowered from <1/3 of vessel length to <1/4 of vessel length; for moderate calcium from between 1/3 and 2/3 of vessel length to between 1/4 and 1/2 of vessel length, and for severe calcium from 2/3 to 1/2 of vessel length. These lower thresholds were chosen to enhance the sensitivity of the scoring system.

There are several important clinical implications of this study. First and foremost, coronary calcium estimated from existing CT scans, performed for non-coronary indications in the year preceding surgery, may serve as a simple, pragmatic, and cost-effective adjunct to traditional preoperative risk scores. Coronary calcium may be particularly helpful for guiding risk assessment in patients in whom coronary artery calcium is absent or minimal, with corresponding low rates of expected MCE. Conversely, a high burden of coronary calcium may signal higher adverse perioperative outcomes, even in patients with a low RCRI. For example, in the present cohort, the incidence of perioperative MCE occurred in 1 in every 22 hospitalizations among patients with an RCRI of 0 and higher ECCB ≥3, versus only 1 in every 71 hospitalizations for those with an RCRI of 0 and lower ECCB <3.

Associations between ECCB and MCE were consistent across age and RCRI subgroups. Notably, we observed a trend toward substantial excess risk associated with coronary calcium among younger patients <65 years old who had a high RCRI ≥3. Furthermore, although the RCRI generally selects for high-risk patients in whom additional cardiac testing may be recommended prior to surgery, a low ECCB in this setting may identify a subset at substantially lower risk of perioperative MCE and in whom additional testing may not be warranted.

Second, coronary artery calcifications were present in 60% of adults age ≥45 undergoing non-cardiac surgery in this study. Despite the high prevalence, coronary calcification is frequently under-reported. Prior studies identified that 31-56% of radiology reports failed to report coronary calcium from non-gated chest CT studies when it was present.^26,27 Our findings support the emphasis in guidelines to report coronary calcium on non-gated chest CT studies.²⁵ Deep learning models have been used to automate calcium scoring on non-gated CT imaging, which may lead to more widespread incorporation of calcium scores in chest CT reporting.²⁸ The NOTIFY-1 study demonstrated that automated CAC detection using a deep learning algorithm from non-ECG gated CT imaging led to significant increases in statin prescriptions.²⁹ In the future, the application of similar machine learning approaches to automatically quantify coronary calcium from pre-existing chest imaging may also be used to inform perioperative risk prediction.

Third, although mild calcium detected by non-contrast imaging was associated with increases in perioperative MCE, contrast-enhanced imaging was less reliable to detect lower levels of coronary calcium and its association with outcomes. This is an expected finding that is consistent with prior studies that report contrast-enhanced CT imaging may miss subtle coronary calcium.³⁰ Contrast in the coronary arteries and adjacent structures can potentially camouflage small foci of calcium, particularly for patients with lower calcium scores.³⁰ Therefore, when preoperative non-contrast and contrast CT scans are both available, non-contrast studies should be preferentially reviewed. Even so, contrast-enhanced images with a higher ECCB were still associated with perioperative MCE.

Finally, we demonstrated that novice CT readers with limited training can reliably estimate coronary calcium from non-ECG gated CT imaging that confers important prognostic associations in the perioperative period. This demonstrates the potential for broad applicability of this approach to risk stratification among clinicians without extensive training in CT imaging.

Study Limitations

There are some notable limitations of this study. First, this was a retrospective cohort study and events were identified and adjudicated through review of the electronic medical record. Second, systematic troponin surveillance was not performed, and because symptoms associated with ischemia may be masked by anesthesia and analgesia in the perioperative period, the incidence of MI may be underestimated. Similarly, perioperative biomarkers for risk stratification were not routinely measured, and the performance of the ECCB in addition to clinical risk scores and hs-troponin or NT-proBNP prior to surgery could not be evaluated and requires further study. Third, this was a highly selected population of patients with clinically-indicated chest CT imaging in the year prior to surgery and the findings of this pragmatic study may not be applicable to other patient populations. Still, these analyses demonstrate the value of leveraging existing CT to glean important prognostic data without the costs of additional testing dedicated for cardiovascular risk stratification. Fourth, coronary calcium is not a perfect surrogate for coronary risk, and the absence of calcium cannot exclude non-calcified atherosclerotic plaques, particularly in younger individuals. Fifth, we included contrast-enhanced CT imaging in our analyses, which may limit the accurate detection of small foci of coronary calcium, especially when located near contrast-enhanced structures (e.g., coronary arteries themselves or other cardiac chambers). However, inclusion of contrast studies made this study pragmatic and broadly applicable to a larger number of patients, as many patients will have only contrast-enhanced CT imaging for review at the time of preoperative risk assessment. Sixth, the RCRI was initially validated to predict a composite of cardiac complications, including myocardial infarction, pulmonary edema, ventricular fibrillation or primary cardiac arrest, and complete heart block; all-cause mortality was not included as an endpoint in RCRI derivation. Accordingly, the performance of the RCRI to predict our clinically relevant definition of MCE (perioperative MI or death) in the current analysis may be suboptimal. Still, this distinction reinforces the notion that the ECCB and RCRI are complementary perioperative risk indicators that may be used to better predict MCE. Lastly, we used a semi-quantitative visual scoring system to estimate coronary calcification.³¹ Although this may be less reliable than formal Agatston scoring for coronary calcium, it provides a practical approach to enhance risk assessment that can be quickly performed by the clinician at the time of preoperative evaluation. In addition, visual scoring of coronary calcium has been shown to have good agreement with formal CAC scoring, even when interpreting from low-dose non-gated CT scans.^19,21

CONCLUSION

Prevalence and severity of coronary calcium from preexisting, preoperative, non-gated chest CT imaging was associated with stepwise increases in perioperative MCE after major, non-cardiac surgery. Since many patients have had recent non-gated CT chest imaging prior to the time of preoperative risk assessment, this measure of coronary calcium may enhance clinical risk stratification prior to non-cardiac surgery.

CLINCICAL PERSPECTIVES.

What Is New?

• A simple semi-quantitative scoring of coronary artery calcium, the estimated coronary calcium burden (ECCB), can be derived from non-gated CT chest imaging with good inter-reader reliability.

• Higher ECCB values from non-gated CT studies were associated with stepwise increases in perioperative death or myocardial infarction after non-cardiac surgery.

• Addition of ECCB to a model with the RCRI improved the C-statistic for perioperative major clinical events.

What Are the Clinical Implications?

• The estimated coronary calcium burden is a pragmatic approach to enhance perioperative risk stratification for patients who have had non-gated CT chest imaging performed within 1 year prior to non-cardiac surgery.

• The ECCB can improve preoperative risk assessments without the need for additional imaging or added cost to the healthcare system.

ABBREVIATIONS AND ACRONYMS:

CT

computed tomography

CAC

coronary artery calcium

ECG

electrocardiographic

MCE

major clinical events

RCRI

Revised Cardiac Risk Index

ECCB

estimated coronary calcium burden

PCI

percutaneous coronary intervention

CABG

coronary artery bypass grafting

ICC

intraclass correlation coefficient

aOR

adjusted odds ratio

IQR

interquartile range