Addition of FFRct in the diagnostic pathway of patients with stable chest pain to reduce unnecessary invasive coronary angiography (FUSION) : Rationale and design for the multicentre, randomised, controlled FUSION trial.

BACKGROUND: Coronary computed tomography angiography (CCTA) is widely used in the diagnostic work-up of patients with stable chest pain. CCTA has an excellent negative predictive value, but a moderate positive predictive value for detecting coronary stenosis. Computed tomography-derived fractional flow reserve (FFRct) is a non-invasive, well-validated technique that provides functional assessment of coronary stenosis, improving the positive predictive value of CCTA. However, to determine the value of FFRct in routine clinical practice, a pragmatic randomised, controlled trial (RCT) is required. We will conduct an RCT to investigate the impact of adding FFRct analysis in the diagnostic pathway of patients with a coronary stenosis on CCTA on the rate of unnecessary invasive coronary angiography, cost-effectiveness, quality of life and clinical outcome. METHODS: The FUSION trial is a prospective, multicentre RCT that will randomise 528 patients with stable chest pain and anatomical stenosis of ≥ 50% but < 90% in at least one coronary artery of ≥ 2 mm on CCTA, to FFRct-guided care or usual care in a 1:1 ratio. Follow-up will be 1 year. The primary endpoint is the rate of unnecessary invasive coronary angiography within 90 days. CONCLUSION: The FUSION trial will evaluate the use of FFRct in stable chest pain patients from the Dutch perspective. The trial is funded by the Dutch National Health Care Institute as part of the research programme 'Potentially Promising Care' and the results will be used to assess if FFRct reimbursement should be included in the standard health care package.

Appropriate use criteria for optical coherence tomography guidance in percutaneous coronary interventions : Recommendations of the working group of interventional cardiology of the Netherlands Society of Cardiology.

INTRODUCTION: Optical coherence tomography (OCT) enables detailed imaging of the coronary wall, lumen and intracoronary implanted devices. Responding to the lack of specific appropriate use criteria (AUC) for this technique, we conducted a literature review and a procedure for appropriate use criteria. METHODS: Twenty-one of all 184 members of the Dutch Working Group on Interventional Cardiology agreed to evaluate 49 pre-specified cases. During a meeting, factual indications were established whereupon members individually rated indications on a 9-point scale, with the opportunity to substantiate their scoring. RESULTS: Twenty-six indications were rated 'Appropriate', eighteen indications 'May be appropriate', and five 'Rarely appropriate'. Use of OCT was unanimously considered 'Appropriate' in stent thrombosis, and 'Appropriate' for guidance in PCI, especially in distal left main coronary artery and proximal left anterior descending coronary artery, unexplained angiographic abnormalities, and use of bioresorbable vascular scaffold (BVS). OCT was considered 'Rarely Appropriate' on top of fractional flow reserve (FFR) for treatment indication, assessment of strut coverage, bypass anastomoses or assessment of proximal left main coronary artery. CONCLUSIONS: The use of OCT in stent thrombosis is unanimously considered 'Appropriate' by these experts. Varying degrees of consensus exists on the appropriate use of OCT in other settings.

Plaque type and composition as evaluated non-invasively by MSCT angiography and invasively by VH IVUS in relation to the degree of stenosis.

BACKGROUND: Imaging of coronary plaques has traditionally focused on evaluating degree of stenosis, as the risk for adverse cardiac events increases with stenosis severity. However, the relation between plaque composition and severity of stenosis remains largely unknown. OBJECTIVE: To assess plaque composition (non-invasively by multislice computed tomography (MSCT) angiography and invasively by virtual histology intravascular ultrasound (VH IVUS)) in relation to degree of stenosis. METHODS: 78 patients underwent MSCT (identifying three plaque types; non-calcified, calcified, mixed) followed by invasive coronary angiography and VH IVUS. VH IVUS evaluated plaque burden, minimal lumen area and plaque composition (fibrotic, fibro-fatty, necrotic core, dense calcium) and plaques were classified as fibrocalcific, fibroatheroma, thin-capped fibroatheroma (TCFA), pathological intimal thickening. For each plaque, percentage stenosis was evaluated by quantitative coronary angiography. Significant stenosis was defined >50% stenosis. RESULTS: Overall, 43 plaques (19%) corresponded to significant stenosis. Of the 227 plaques analysed, 70 were non-calcified plaques (31%), 96 mixed (42%) and 61 calcified (27%) on MSCT. Plaque types on MSCT were equally distributed among significant and non-significant stenoses. VH IVUS identified that plaques with significant stenosis had higher plaque burden (67% (11%) vs 53% (12%), p<0.05) and smaller minimal lumen area (4.6 (3.8-6.8) mm(2) vs 7.3 (5.4-10.5) mm(2), p<0.05). Interestingly, no differences were observed in percentage fibrotic, fibro-fatty, necrotic core and dense calcium. Non-significant stenoses were more frequently classified as pathological intimal thickening (46 (25%) vs 3 (7%), p<0.05), although TCFA (more vulnerable plaque) was distributed equally (p = 0.18). CONCLUSION: No evident association exists between the degree of stenosis and plaque composition or vulnerability, as evaluated non-invasively by MSCT and invasively by VH IVUS.

Multislice computed tomography coronary angiography for risk stratification in patients with an intermediate pretest likelihood.

OBJECTIVES: To assess whether multislice computed tomography coronary angiography (MSCTA) may be useful for risk stratification of patients with suspected coronary artery disease (CAD) at intermediate pretest likelihood according to Diamond and Forrester. DESIGN AND PATIENTS: MSCTA images were evaluated for the presence of significant CAD in 316 patients with suspected CAD (60% male, average (SD) age 57 (11) years) and an intermediate pretest likelihood according to Diamond and Forrester. Patients were followed up to determine the occurrence of an event. MAIN OUTCOME MEASURES: A combined end point of all-cause mortality, non-fatal infarction and unstable angina requiring revascularisation. RESULTS: Significant CAD was seen in 89 patients (28%), whereas normal MSCTA or non-significant CAD was seen in the remaining 227 (72%) patients. During follow-up (median 621 days (25-75th centile 408-835) an event occurred in 13 patients (4.8%). The annualised event rate was 0.8% in patients with normal MSCT, 2.2% in patients with non-significant CAD and 6.5% in patients with significant CAD. Moreover, MSCTA remained a significant predictor (p<0.05) of events after multivariate correction (hazard ratio = 3.460 (95% CI 1.142 to 10.480). CONCLUSIONS: The results suggest that in patients with an intermediate pretest likelihood, MSCTA is highly effective in re-stratifying patients into either a low or high post-test risk group. These results further emphasise the usefulness of non-invasive imaging with MSCTA in this patient population.

Prevalence of coronary artery disease and plaque morphology assessed by multi-slice computed tomography coronary angiography and calcium scoring in asymptomatic patients with type 2 diabetes.

OBJECTIVE: The purpose of the study was to evaluate the prevalence of CAD as well as plaque morphology in asymptomatic patients with type 2 diabetes using multi-slice computed tomography (MSCT). In addition, the relation between calcium score and MSCT findings was explored. DESIGN: In 70 patients, coronary calcium scoring and non-invasive coronary angiography were performed. Angiograms showing atherosclerosis were further classified as obstructive (> or =50% luminal narrowing) CAD or not. Plaque type (non-calcified, mixed and calcified) was determined. Finally, the relation between calcium score and MSCT findings was explored. RESULTS: A calcium score <10 was observed in 31 (44%) patients. A calcium score of 10-100 was observed in 14 (20%) patients while a score of 101-400 or >400 was identified in 12 (17%) and 13 (19%) patients respectively. Non-invasive coronary angiography showed CAD in 56 (80%) patients. 322 coronary segments with plaque were identified, of which 132 (41%) contained non-calcified plaques, 65 (20%) mixed plaques and 125 (39%) calcified plaques. The percentage of patients with obstructive CAD paralleled increasing calcium score. The presence of CAD was noted in 17 (55%) patients with no or minimal calcium (score <10). CONCLUSIONS: MSCT angiography detected a high prevalence of CAD in asymptomatic patients with type 2 diabetes. A relatively high proportion of plaques were non-calcified (41%). Importantly, a calcium score <10 did not exclude CAD in these patients. MSCT might be a useful technique to identify CAD in asymptomatic patients with type 2 diabetes with incremental value over calcium scoring.

Gender influence on the diagnostic accuracy of 64-slice multislice computed tomography coronary angiography for detection of obstructive coronary artery disease.

OBJECTIVE: To compare the diagnostic accuracy of 64-slice multislice computed tomography (MSCT) coronary angiography between female and male patients using conventional coronary angiography as the reference standard. DESIGN: Diagnostic accuracy study. SETTING: University hospital. PATIENTS: 103 consecutive patients (51 men, 52 women, mean (SD) age 60 (10) years) with known and suspected coronary artery disease underwent 64-slice MSCT. MAIN OUTCOME MEASURES: Diagnostic accuracy of 64-slice MSCT to detect obstructive (>or=50% luminal narrowing) stenoses in men and women. RESULTS: One male and two female patients were excluded from the analysis owing to non-diagnostic MSCT scans as a result of increased heart rate and breathing during the scan. Accordingly, on segmental level, 728/762 coronary segments were of sufficient quality in women (96% (95% CI 95% to 97%)) and 704/723 segments were interpretable in men (97% (95% CI 96% to 98%)). In the remaining 100 patients included in the further analyses, the sensitivity and specificity on a segmental level in women and men were 85% (95% CI 75% to 95%) vs 85% (95% CI 78% to 92%) and 99% (95% CI 98% to 100%) vs 99% (95% CI 98% to 100%), respectively. On a patient level, the sensitivity in women and men was 95% (95% CI 87% to 100%) vs 100%, specificity 93% (95% CI 83% to 100%) vs 89% (95% CI 74% to 100%), positive predictive value 91% (95% CI 79% to 100%) vs 94% (95% CI 86% to 100%), and negative predictive value 96% (95% CI 89% to 100%) vs 100%, respectively. CONCLUSION: The findings confirm the high diagnostic accuracy of 64-slice MSCT coronary angiography in both male and female patients.