Impact of Stress CT Myocardial Perfusion on Downstream Resources and Prognosis (CTP-PRO)

Impact of Stress Cardiac Computed Tomography Myocardial Perfusion on Downstream Resources and PROgnosis in Patients With Suspected or Known Coronary Artery Disease: a Multicenter International Study

Medical University of South Carolina, Semmelweis University Heart and Vascular Center, Emory University, UMC Utrecht, Johns Hopkins University, Policlinico Hospital

CT myocardial perfusion imaging (CTP) represents one of the newly developed CT-based techniques but its cost-effectiveness in the clinical pathway is undefined. The aim of the study is to evaluate the usefulness of combined evaluation of coronary anatomy and myocardial perfusion in intermediate to high-risk patients for suspected CAD or with known disease in terms of clinical decision-making, resource utilization and outcomes in a broad variety of geographic areas and patient subgroups.

The use of cardiac computed tomography angiography (CCTA) is usually suggested in low to intermediate risk for its diagnostic and prognostic role to rule out CAD with low radiation exposure. In the setting of intermediate to high risk patients, the addition of functional information is prognostically useful and, in patients with previous history of percutaneous coronary intervention (PCI), functional strategy has been shown to be more cost-effective as compared to anatomical assessment CT myocardial perfusion imaging (CTP) represents one of the newly developed CT-based techniques, combining both anatomical and functional evaluation of CAD in a single imaging modality. More recently, stress CTP was shown to provide additional diagnostic value as compared to CCTA alone in intermediate to high risk patients. The purpose of this study will be to evaluate the usefulness and impact of combined evaluation of coronary artery anatomy and myocardial perfusion with CCTA+CTP in intermediate to high risk patients for suspected CAD or with known disease in terms of clinical decision-making, resource utilization, and outcomes in a broad variety of geographic areas and patient subgroups. CTP-PRO study is a cooperative, international, multicentre, prospective, open-label, randomized controlled study evaluating the cost-effectiveness of a CCTA+CTP strategy versus usual care in intermediate to high risk patients with suspected or known CAD who undergo clinically indicated diagnostic evaluation. Patients will be screened for study eligibility. Patients meeting all selection criteria will be asked to sign an informed consent document prior to undergoing any study-specific evaluation; then a structured interview will be performed and a clinical history obtained, assessing the presence of common cardiac risk factors, drug therapy (focus on statin, aspirin and/or antiplatelet agent use) and symptoms (typical or atypical angina, to estimate the pre-test likelihood of CAD). Upon completion of the screening procedure and enrollment, the patients will be randomized 1:1 to the CT-based strategy (Group A) or usual care (Group B). Patient follow-up will be performed at 1 year (± 1 month) and 2 years (± 1 month) by trained interviewers who check medical records or by phone interview collecting the following information: downstream testing; overall radiation exposure; outcomes; cost-effectiveness estimation. The primary endpoint of the study is the reclassification rate of CCTA in group B due to the addition of CTP. The secondary endpoint will be the comparison between group A and group B in terms of non-invasive and invasive downstream testing, prevalence of obstructive CAD at ICA, revascularization, cumulative ED and overall cost during the follow-up at 1- and 2-years. The tertiary endpoint will be the comparison between each group in terms of MACE and cost-effectiveness at 1- and 2-years.

Upon completion of the screening procedure and enrollment, the patients will be randomized 1:1 to the CT-based strategy (Group A) or usual care (Group B).

CCTA will be performed with one of the latest generation scanners. A stenosis > 50% will be considered as significant from an anatomical point of view. For coronary stents, degree of intrastent restenosis will be evaluated by visual assessment of intraluminal contrast density. ISR > 50% will be considered as significant from an anatomical point of view. For CABG, each graft will be visually evaluated and scored as patent, non-significant stenosis ≤ 50%, significant stenosis > 50%, or occluded. For patients with positive CCTA results, additional stress CTP will be performed subsequently. If indicated, vasodilatation will be induced with i.v. adenosine injection or regadenoson. Static or dynamic CTP will be performed according to local practice and scanner technology available. For all patients with previous history of MI the presence of reversible ischemia will be obtained by the comparison between rest and stress perfusion.

Patients randomized to this group will be evaluated according to current clinical guidelines with the following approaches: (a) stress ECG, or imaging-based tests such as Stress Echo, Stress CMR, SPECT or PET; (b) direct referral to ICA.

When judged indicated, functional assessment with stress CTP perfusion will be performed on top of CCTA.

(a) functional non-invasive tests (stress ECG, or imaging-based tests such as Stress Echo, Stress CMR, SPECT or PET) as a gatekeeper for ICA; (b) direct referral to ICA.

For each enrolled patient in whom both CCTA and stress CTP will be performed, the endpoint review committee will use data from coronary CTA and CTP, along with the clinical data to determine the management plan using the following criteria: (a) optimal medical therapy, (b) more non-invasive information required, (c) invasive evaluation required, (d) revascularization treatment (PCI or CABG or hybrid treatment).

Comparison between group A and group B in terms of number of non-invasive downstream testing (Exercise EKG, Stress-Echo, SPECT, Stress CMR, PET) or invasive testing (invasive coronary angiography) performed after the randomization.

Comparison between group A and group B in terms of number of downstream invasive testing (invasive coronary angiography) performed after the randomization.

Comparison between group A and group B in terms of number of patients treated with revascularization (PCI or CABG or hybrid treatment).

Comparison between group A and group B in terms of cumulative Effective Dose (ED), measured in mSv, due to non-invasive or invasive testing performed after randomization.

Comparison between group A and group B in terms of overall costs of downstream diagnostic tests (sum of costs of all diagnostic tests performed after randomization), expressed in Dollars, according to local reimbursement.

Comparison between group A and group B group in terms of number of patients that needed hospitalization for cardiac reason.

Comparison between group A and group B group in terms of number of patients that needed hospitalization for unstable angina (defined according to 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2016:37,267-315).

Comparison between group A and group B group in terms of number of patients that experienced non-fatal myocardial infarction (defined according to Fourth universal definition of myocardial infarction, 2018. Eur Heart J 2019:40,237-269).

Comparison between group A and group B group in terms of number of patients that experienced death because of immediate cardiac cause (e.g., MI, low-output failure, fatal arrhythmia) or vascular cause (e.g., cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular cause). Unwitnessed death and death of unknown cause will be classified as cardiovascular death.

Cost-effectiveness ratio will be calculated according to the following equation: (Index test cost + downstream diagnostic tests cost) / projected remaining life expectancy.

Inclusion Criteria: Consecutive patients (age ≥ 18 years) with known or suspected CAD referred for clinically indicated diagnostic evaluation. CCTA has to be performed with the state of art in terms of scanner technology as follow: Revolution CT (GE Healthcare, Milwaukee, WI), CardioGraphe (Arineta, Caesarea, Israel), SOMATOM Force (Siemens, Forchheim, Germany), Brilliance iCT and IQon CT (Philips, Best, Netherlands), Aquilion One Vision (Toshiba Medical Systems Corp., Otawara, Japan). Exclusion Criteria: Performance of any non-invasive diagnostic testing within 90 days before enrollment Low to intermediate pre-test likelihood of CAD according to the updated Diamond-Forrester risk model score Acute coronary syndrome Need for an emergent procedure Evidence of clinical instability Contra-indication to contrast agent administration and/or impaired renal function Inability to sustain a breath hold Pregnancy Cardiac arrhythmias Presence of pace maker or implantable cardioverter defibrillator Contra-indications to the administration of sub-lingual nitrates, beta-blockade and adenosine Structural cardiomyopathy outside of suspected or know ischemic heart disease

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