Contrast Enhanced Cardiac CT Reveals Coronary Artery Disease in 45% Of Asymptomatic Allogeneic Stem Cell Transplantation Long-Term Survivors

Long term survivors of allogeneic stem cell transplantation (allo-SCT) face a 2-3 fold increased risk of premature cardiovascular (CV) related death compared to the general population^1-3. After allo-SCT chronic inflammation and endothelial damage from GvHD, immunosuppression, hypogonadism, and metabolic syndrome compound with classical cardiovascular risk factors such as diabetes, dyslipidemia, hypertension, and renal disease to augment cardiovascular risk^4-6. A reliable screening strategy to identify allo-SCT survivors at risk for CV-related disease is therefore warranted to anticipate and prevent future events. Cardiac computed tomography (CCT) is an emerging non-invasive imaging technology with high sensitivity for detecting coronary artery disease (CAD) and high negative predictive value to exclude the presence of CAD.⁷ Coronary artery calcium (CAC) is a marker of atherosclerosis, which can be quantified by CCT, and is proportional to the extent and severity of atherosclerotic disease⁷.

We conducted the first prospective non-randomized single institution study to evaluate Agatston coronary calcium scoring (CCS) by CCT with concomitant coronary CT angiograms (CCTA) as a tool to identify the survivors at risk for CV disease. Twenty asymptomatic post allo-SCT survivors underwent CCS and contrast enhanced CCTA at a median follow up of 6 years post transplant. Patient characteristics are shown in Table 1. Ten-year Framingham cardiovascular risk scores (FRS) were also calculated at time of screening. Subjects were prepared for coronary CTA according to standard guidelines⁸.

Table 1.

Patient characteristics

Age at study : Median (range)	46 (25-74) years
Females	5
Median follow-up (range)	6 (5- 17) years
Disease :
AML / MDS	11
CML	5
ALL / CLL	2
NHL / MM	2
Hypertension at study	6
Diabetes Mellitus at study	3
Median BMI (range) kg/m2	30.9 (23.4-44.9)
Smoking pre transplant	5
Smoking post transplant	1
hsCRP at study median (range)	2.81 (0.79 -4.61)

ALL - Acute lymphoid leukemia, AML - Acute myeloid leukemia, BMI- Body mass index, CAD- Coronary artrey disease, CLL - Chronic lymphoid leukemia, CML - Chronic myeloid leukemia, hs CRP - High sensitivity C-reactive protein MDS - Myelodysplastic syndrome, MM - Multiple myeloma, NHL- Non-Hodgkin’s lymphoma

Non-obstructive CAD was detected in eight (45%) patients, and obstructive CAD in one (5%). Two (22.2%) of these had single vessel disease, three (33.3%) had two vessel disease, and four (44.5%) had triple vessel disease. Additionally, five (55.5%) of these subjects had aortic root calcification. Lesion distributions by arterial territory were: left main 8.7%, left anterior descending 35%, left circumflex 26% and right coronary artery 30.4%. Characteristics of coronary plaques were: 48% calcified, 48% mixed calcified / non-calcified, and 4% non-calcified. In those with CAD, the median coronary calcium score was 55 (range: 0-5110) (p<0.001), corresponding to the 75^th percentile (range: 33^rd to 99^th percentile) (p < 0.001) adjusted for age, gender, and ethnicity. In comparison, those with no CAD had a median CCS of 0, < 1 percentile. One patient with <1% FRS had a zero coronary calcium score with non-obstructive CAD (mixed plaque) on the CCTA. The radiation exposure during the procedure was acceptable, at a median of 0.78 mSv (range 0.18 to 3.12 mSv) for the CCS and 1.15 mSv (range 0 to 8.01) for the CCTA. There were no complications related to the procedure.

Standard cardiac risk factors are used by FRS to determine the 10-year risk of developing cardiovascular disease in an individual with no known cardiovascular disease. It is well established that CCS adds independent prognostic information to that obtained by FRS⁹. Current (2010 AHA/ACC) guidelines suggest a role for CCS for screening asymptomatic non-transplant individuals with intermediate Framingham risk¹⁰. However in this group of post allo-SCT survivors we detected CAD in 4 of 15 (26.6%) patients who would be considered “low risk” by conventional FRS stratification. This suggests a potential role for screening all patients post allo-SCT regardless of FRS. CCS alone (sensitivity of 89% and specificity of 100%) may be adequate for screening and avoids the use of IV contrast.

We conclude that CCS with or without CCTA is a safe, feasible, highly sensitive method to evaluate cardiovascular risk in asymptomatic low FRS transplant survivors. Such individuals may benefit by earlier intervention to prevent cardiovascular events. Factors contributing to increased cardiovascular risk detected by this sensitive approach will now be explored in a larger patient cohort.