Trial Outcomes & Findings for Validation of a Computed Tomography (CT) Based Fractional Flow Reserve (FFR) Software Using the 320 Detector Aquilion ONE CT Scanner. (NCT NCT03149042)

NCT ID: NCT03149042

Last Updated: 2020-11-17

Results Overview

Patient CCTA images were imported into Vitrea segmentation software (Vital Images, Minnetonka, MN) for use in the research-based CT based FFR algorithm. The software analyzes four data volumes acquired a 70%, 80%, 90% and 99% of the R-R interval and computes the FFR based on the changes in vessel diameter and computational fluid dynamics. Within the algorithm, the aortic root and three main coronary arteries (LAD, LCX, and RCA) were automatically segmented, and then manually adjusted to obtain accurate centerline and contours. The CT based FFR was calculated and the user adjusted the location of the distal pressure measurement to calculate the CT basedFFR at the same location as Invasive-FFR, two lesion lengths below the distal end of the lesion. Area under the Receiver Operator Characteristic were measured where an Invasive FFR\<=0.8 was considered positive.

• Recruitment status: COMPLETED
• Target enrollment: 75 participants
• Primary outcome timeframe: 24 hours
• Results posted on: 2020-11-17

Participant Flow

Participant milestones

Measure	CCTA Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA (Coronary CT angiography) Diagnostic Test
Overall Study STARTED	75
Overall Study COMPLETED	52
Overall Study NOT COMPLETED	23

Reasons for withdrawal

Measure	CCTA Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA (Coronary CT angiography) Diagnostic Test
Overall Study Invasive FFR not performed	21
Overall Study Poor CT Image Quality	1
Overall Study Invasive FFR Measurement cancelled	1

Baseline Characteristics

Validation of a Computed Tomography (CT) Based Fractional Flow Reserve (FFR) Software Using the 320 Detector Aquilion ONE CT Scanner.

Baseline characteristics by cohort

Measure	CCTA n=52 Participants Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA Coronary: Diagnostic Test
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants
Age, Categorical >=65 years	30 Participants n=5 Participants
Age, Continuous	64.7 years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	52 Participants n=5 Participants
Region of Enrollment United States	17 Participants n=5 Participants
Region of Enrollment Japan	35 Participants n=5 Participants
BMI	25.2 kg/m^2 STANDARD_DEVIATION 3.9 • n=5 Participants
Coronary Calcium Score	385 Coronary Calcium Score STANDARD_DEVIATION 388 • n=5 Participants
FFR FFR>0.8	29 Participants n=5 Participants
FFR FFR<=0.8	23 Participants n=5 Participants
Diabetes Mellitus Yes	22 Participants n=5 Participants
Diabetes Mellitus No	30 Participants n=5 Participants
Hypertension Yes	33 Participants n=5 Participants
Hypertension No	19 Participants n=5 Participants
Hyperlipidemia Yes	38 Participants n=5 Participants
Hyperlipidemia No	14 Participants n=5 Participants
Smoking Former	16 Participants n=5 Participants
Smoking Current	10 Participants n=5 Participants
Smoking Never	26 Participants n=5 Participants
Prior Myocardial Infarction Yes	4 Participants n=5 Participants
Prior Myocardial Infarction No	48 Participants n=5 Participants
Creatinine	0.83 mg/ dl STANDARD_DEVIATION 0.45 • n=5 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: From the total number of patients, nine patients had multi-vessel disease and I-FFR was measured in two vessels. In total I-FFR was measured in: 42 LADs, 11 LCXs and 8 RCAs. Invasive -FFR measurement location was from the ostium to two lesion lengths below the distal throat of the lesion .

Patient CCTA images were imported into Vitrea segmentation software (Vital Images, Minnetonka, MN) for use in the research-based CT based FFR algorithm. The software analyzes four data volumes acquired a 70%, 80%, 90% and 99% of the R-R interval and computes the FFR based on the changes in vessel diameter and computational fluid dynamics. Within the algorithm, the aortic root and three main coronary arteries (LAD, LCX, and RCA) were automatically segmented, and then manually adjusted to obtain accurate centerline and contours. The CT based FFR was calculated and the user adjusted the location of the distal pressure measurement to calculate the CT basedFFR at the same location as Invasive-FFR, two lesion lengths below the distal end of the lesion.

Area under the Receiver Operator Characteristic were measured where an Invasive FFR<=0.8 was considered positive.

Outcome measures

Measure	CCTA n=61 Coronary Arteries Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA Coronary: Diagnostic Test
Comparison of CT Based FFR With Invasive FFR, ROC Analysis	0.8 probability of accurate diagnosis Interval 0.7 to 0.87

PRIMARY outcome

Timeframe: 24 hours

Population: From the total number of patients, nine patients had multi-vessel disease and I-FFR was measured in two vessels. In total I-FFR was measured in: 42 LADs, 11 LCXs and 8 RCAs. Invasive -FFR measurement location was from the ostium to two lesion lengths below the distal throat of the lesion .

Patient CCTA images were imported into Vitrea segmentation software (Vital Images, Minnetonka, MN) for use in the research-based CT based FFR algorithm. The software analyzes four data volumes acquired a 70%, 80%, 90% and 99% of the R-R interval and computes the FFR based on the changes in vessel diameter and computational fluid dynamics. Within the algorithm, the aortic root and three main coronary arteries (LAD, LCX, and RCA) were automatically segmented, and then manually adjusted to obtain accurate centerline and contours. The CT based FFR was calculated and the user adjusted the location of the distal pressure measurement to calculate the CT basedFFR at the same location as Invasive-FFR, two lesion lengths below the distal end of the lesion.

Pearson Correlation between Invasive FFR and CT based FFR was measured

Outcome measures

Measure	CCTA n=61 Coronary Arteries Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA Coronary: Diagnostic Test
Comparison of CT Based FFR With Invasive FFR, Correlation Analysis	0.75 correlation coefficient Interval 0.62 to 0.85

PRIMARY outcome

Timeframe: 24 hours

Population: From the total number of patients, nine patients had multi-vessel disease and I-FFR was measured in two vessels. In total I-FFR was measured in: 42 LADs, 11 LCXs and 8 RCAs. Invasive -FFR measurement location was from the ostium to two lesion lengths below the distal throat of the lesion .

Patient CCTA images were imported into Vitrea segmentation software (Vital Images, Minnetonka, MN) for use in the research-based CT based FFR algorithm. The software analyzes four data volumes acquired a 70%, 80%, 90% and 99% of the R-R interval and computes the FFR based on the changes in vessel diameter and computational fluid dynamics. Within the algorithm, the aortic root and three main coronary arteries (LAD, LCX, and RCA) were automatically segmented, and then manually adjusted to obtain accurate centerline and contours. The CT based FFR was calculated and the user adjusted the location of the distal pressure measurement to calculate the CT basedFFR at the same location as Invasive-FFR, two lesion lengths below the distal end of the lesion.

Sensitivity were measured where an Invasive FFR<=0.8 was considered positive. Sensitivity reflects the percentage of true positive cases identified by CT-FFR compared to I-FFR

Outcome measures

Measure	CCTA n=61 Coronary Arteries Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA Coronary: Diagnostic Test
Comparison of CT Based FFR With Invasive FFR, Sensitivity	82.61 percentage of true positive cases

PRIMARY outcome

Timeframe: 24 hours

Population: From the total number of patients, nine patients had multi-vessel disease and I-FFR was measured in two vessels. In total I-FFR was measured in: 42 LADs, 11 LCXs and 8 RCAs. Invasive -FFR measurement location was from the ostium to two lesion lengths below the distal throat of the lesion .

Patient CCTA images were imported into Vitrea segmentation software (Vital Images, Minnetonka, MN) for use in the research-based CT based FFR algorithm. The software analyzes four data volumes acquired a 70%, 80%, 90% and 99% of the R-R interval and computes the FFR based on the changes in vessel diameter and computational fluid dynamics. Within the algorithm, the aortic root and three main coronary arteries (LAD, LCX, and RCA) were automatically segmented, and then manually adjusted to obtain accurate centerline and contours. The CT based FFR was calculated and the user adjusted the location of the distal pressure measurement to calculate the CT basedFFR at the same location as Invasive-FFR, two lesion lengths below the distal end of the lesion.

Specificity was measured, where an Invasive FFR<=0.8 was considered positive. Specificity reflects the percentage of true negative cases identified by CT-FFR compared to I-FFR

Outcome measures

Measure	CCTA n=61 Coronary Arteries Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA Coronary: Diagnostic Test
Comparison of CT Based FFR With Invasive FFR, Specificity	76.32 percentage of of true negative cases

SECONDARY outcome

Timeframe: 4 weeks from baseline

Population: From the total number of patients, nine patients had multi-vessel disease and Invasive-FFR was measured in two vessels. In total I-FFR was measured in: 42 LADs, 11 LCXs and 8 RCAs. Bench-top FFR was measured at the same locations as Invasive -FFR, from the ostium to two lesion lengths below the distal throat of the lesion .

CT images were used to measure CT-FFR and to generate patient-specific 3D printed models of the aortic root and three main coronary arteries. Each patient-specific 3D printed model was connected to a programmable pulsatile pump and bench-top FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for hyperemic", 500 mL/min by adjusting the model's distal coronary resistance. Linear regression and Pearson correlation was calculated.

Outcome measures

Measure	CCTA n=61 Coronary Arteries Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA Coronary: Diagnostic Test
Comparison of CT Based FFR With Bench-top FFR Using 3D Printed Patient Specific Phantoms	0.64 correlation coefficient Interval 0.46 to 0.76

SECONDARY outcome

Timeframe: 4 weeks from baseline

Population: From the total number of patients, nine patients had multi-vessel disease and Invasive-FFR was measured in two vessels. In total I-FFR was measured in: 42 LADs, 11 LCXs and 8 RCAs. Bench-top FFR was measured at the same locations as Invasive -FFR, from the ostium to two lesion lengths below the distal throat of the lesion .

CT images were used to create patient specific 3d-printed phantom. Each patient-specific 3D printed model was connected to a programmable pulsatile pump and benchtop FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for hyperemic", 500 mL/min by adjusting the model's distal coronary resistance. Benchtop-FFR was compared with Invasive-FFR. Area under the Receiver Operator Characteristic were measured where an Invasive FFR<=0.8 was considered positive.

Outcome measures

Measure	CCTA n=61 Coronary Arteries Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA Coronary: Diagnostic Test
Comparison of Bench-top FFR Using 3D Printed Patient Specific Phantoms With Invasive FFR, ROC Analysis	0.81 probability of accurate diagnosis Interval 0.64 to 0.91

SECONDARY outcome

Timeframe: 4 weeks from baseline

Population: From the total number of patients, nine patients had multi-vessel disease and Invasive-FFR was measured in two vessels. In total I-FFR was measured in: 42 LADs, 11 LCXs and 8 RCAs. Bench-top FFR was measured at the same locations as Invasive -FFR, from the ostium to two lesion lengths below the distal throat of the lesion .

CT images were used to create patient specific 3d-printed phantom. Each patient-specific 3D printed model was connected to a programmable pulsatile pump and benchtop FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for hyperemic", 500 mL/min by adjusting the model's distal coronary resistance. Benchtop-FFR was compared with Invasive-FFR. Pearson Correlation factor was calculated.

Outcome measures

Measure	CCTA n=61 Coronary Arteries Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA Coronary: Diagnostic Test
Comparison of Bench-top FFR Using 3D Printed Patient Specific Phantoms With Invasive FFR, Pearson Correlation	0.71 correlation coefficient Interval 0.56 to 0.81

SECONDARY outcome

Timeframe: 4 weeks from baseline

Population: From the total number of patients, nine patients had multi-vessel disease and Invasive-FFR was measured in two vessels. In total I-FFR was measured in: 42 LADs, 11 LCXs and 8 RCAs. Bench-top FFR was measured at the same locations as Invasive -FFR, from the ostium to two lesion lengths below the distal throat of the lesion .

CT images were used to create patient specific 3d-printed phantom. Each patient-specific 3D printed model was connected to a programmable pulsatile pump and benchtop FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for hyperemic", 500 mL/min by adjusting the model's distal coronary resistance. Benchtop-FFR was compared with Invasive-FFR. Sensitivity was measure, where an Invasive FFR<=0.8 was considered positive.Sensitivity reflects the percentage of true positive cases identified by B-FFR compared to I-FFR

Outcome measures

Measure	CCTA n=61 Coronary Arteries Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA Coronary: Diagnostic Test
Comparison of Bench-top FFR Using 3D Printed Patient Specific Phantoms With Invasive FFR, Sensitivity	86.96 percentage of true positive cases

SECONDARY outcome

Timeframe: 4 weeks from baseline

Population: From the total number of patients, nine patients had multi-vessel disease and Invasive-FFR was measured in two vessels. In total I-FFR was measured in: 42 LADs, 11 LCXs and 8 RCAs. Bench-top FFR was measured at the same locations as Invasive -FFR, from the ostium to two lesion lengths below the distal throat of the lesion .

CT images were used to create patient specific 3d-printed phantom. Each patient-specific 3D printed model was connected to a programmable pulsatile pump and benchtop FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for hyperemic", 500 mL/min by adjusting the model's distal coronary resistance. Benchtop-FFR was compared with Invasive-FFR. Specificity was calculated, where an Invasive FFR<=0.8 was considered positive. Specificity reflects the percentage of true negative cases identified by B-FFR compared to I-FFR

Outcome measures

Measure	CCTA n=61 Coronary Arteries Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. CCTA Coronary: Diagnostic Test
Comparison of Bench-top FFR Using 3D Printed Patient Specific Phantoms With Invasive FFR, Specificity	97.37 percentage of true negative cases

Adverse Events

CCTA Coronary

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Ciprian Ionita

University at Buffalo

Phone: 7164004283

Email: cnionita@buffalo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place