The Value of Fractional Flow Reserve Derived From Coronary CT Angiography as Compared to CCTA or CCTA and Stress MPI in the Triage of Low to Intermediate Emergent Chest Pain Patients With Toshiba CT-FFR

Background:

Coronary Computed Tomography Angiogram (CCTA) is a non-invasive imaging modality that has high sensitivity and negative predictive value for the detection of coronary artery disease (CAD). The main limitations of CCTA are its poor specificity and positive predictive value, as well as its inherent lack of physiologically relevant data on hemodynamic significance of coronary stenosis, a data that is provided either by non-invasive stress tests such as myocardial perfusion imaging (MPI) or invasively by measurement of the Fractional Flow Reserve (FFR). Recent advances in computational fluid dynamic techniques applied to standard CCTA are now emerging as powerful tools for virtual measurement of FFR from CCTA imaging (CT-FFR). These techniques correlate well with invasively measured FFR [1-4]. The primary purpose of this study is to evaluate the incremental benefit CT-FFR as compared to CCTA in triaging chest pain patients in ED settings who are found to have obstructive CAD upon CCTA (generally > 30% and < 90% stenosis). Invasive FFR and short term clinical outcomes (90 days) will be correlated with each diagnostic modality in order to evaluate positive and negative predictive value of each when used incrementally with CCTA.

Investigational Agent:

CCTA is increasingly becoming a preferred non-invasive imaging modality because of its high sensitivity and negative predictive value for the detection of CAD. It has been shown to be a robust imaging modality for evaluation of chest pain, and is associated with decreased unnecessary hospital admission, length of stay, major adverse cardiovascular event rates, recidivism rates, and downstream resource utilization compared to standard evaluation [5]. While findings so far are highly suggestive of CCTA's significance as a gatekeeper for ICA by ruling out obstructive CAD, fewer than half of obstructive stenosis identified by CCTA are ischemia-causing, signifying its poor positive predictive value and inherent lack of physiological information [6-8]. Consequently, utilization of CCTA has not entirely averted need for downstream testing for functional assessment of CCTA-detected obstructive lesions either by stress testing or ICA. Recently a major treatment modality, associated with the use of CCTA, has become available that offers promise for improving positive predictive value and physiological relevant hemodynamic data. Advances in computational fluid dynamic techniques applied to standard CCTA are now emerging as a powerful tool for virtual measurement of FFR from CCTA imaging (CT-FFR). This technique correlates well with invasively measured FFR [1-4]. While HeartFlow, Inc. has established an FDA approved process to assess coronary artery flow using noninvasive CT-FFR, this data requires 24 to 48 hours for processing.

Toshiba CT-FFR processing is non-FDA approved. The analytic method for vessel evaluation differs from that used by HeartFlow. Currently Toshiba is operating studies at four organizations around the world to assess the product's performance. Recently, the company published results from a study conducted Australia that showed positive findings on a sample of 42 patients, with positive predictive value of 74% vs. 60%.[9] The technology was presented at European Society of Cardiology (ESC) by Dr. S. Seneviratne and at Radiological Society of North America (RSNA) and the American Heart Association (AHA). Using the technology for ED patients offers potential advantage over the HeartFlow process, because the turnaround time for the procedure is one to three hours. However, the early positive findings need to be validated with a more robust study.