Short summary

Coronary CT angiography (CCTA) is a non-invasive method with high diagnostic accuracy for detection and exclusion of obstructive coronary artery disease (CAD). The functional relevance of coronary stenosis has been evaluated by fractional flow reserve (FFR), currently accepted as a safe and cost-effective gatekeeper for revascularization. Non-invasive estimation of FFR has become available based on CCTA - FFR-CT. Whereas CCTA has reduced diagnostic performance in patients with severe coronary artery calcification (CAC > 399), the diagnostic and prognostic performance of FFR-CT in these patients have been scantly investigated. The FACC study is the largest study to date addressing the diagnostic performance of FFR-CT in patients with CAC score >399. The present study is a follow-up study of the FACC-study and will evaluate the intermediate term prognostic performance of FFR-CT. 

Rationale

Cardiovascular disease (CVD) is the leading cause of death worldwide, with CAD accounting for half of these deaths. CCTA is a non-invasive method for evaluation of patients with suspected CAD and provides detailed anatomical information with a high sensitivity for detection of obstructive CAD. 

Adverse cardiovascular events in patients with normal findings on CCTA are rare. However, severe CAC causes artefacts inherent to the current CT technology obscuring the vessel volume and reducing the diagnostic accuracy of CTCA. The diagnostic use of CCTA in patients with a CAC score > 399 has thus been questioned, in which other diagnostic modalities such as invasive coronary angiography (ICA) or myocardial perfusion scintigraphy may be considered.

Currently, revascularization is recommended in hemodynamic significant lesions (invasive FFR ? 0.8). Invasive FFR is calculated as blood pressure distally and proximally to a stenosis. FFR is a safe and cost-effective gatekeeper for coronary revascularization. Recently, a new modality able to non-invasively evaluate the hemodynamic significance of

coronary stenosis has been introduced: FFR by CCTA (FFR-CT). Based on the standard CCTA scanning, coronary blood flow and pressure may be computed and a noninvasive FFR derived without additional scanning. Studies have demonstrated that FFR-CT has a high per-patient and per-vessel agreement with invasive FFR. Studies have suggested that FFR-CT has a high diagnostic accuracy in patients with severe CAC (score > 399), however evidence is limited and warrant further evaluation. 

Furthermore, studies suggest that patients with suspected CAD and with FFR-CT values > 0.80, have a favorable short-term prognosis and that FFR-CT guided care is safe. However,  the prognosis in patients with FFR-CT < 0.80 is not sufficiently investigated. Also, the prognostic utility of FFR-CT in patients with severe coronary calcifications has not previously been assessed. Finally, the association between FFR-CT measurements and CAD progression has never been evaluated.

In the FACC-study (OP_335), we compared CCTA and FFR-CT versus invasive coronary angiography (ICA) and FFR in order to determine the clinical utility and diagnostic performance of CCTA and FFR-CT in patients with suspected stable CAD and CAC score > 399. The primary endpoint of the study was per-patient diagnostic performance of FFR-CT. Furthermore, the investigators examined whether CCTA with FFR-CT would safely reduce the number of subsequent ICAs when  used as a gate-keeper to ICA. The FACC study included 260 patients enrolled from September 2016 to December 2017, the largest study to date addressing patients with CAC score > 399.

The present study is a follow-up study of the FACC study. The major objectives are to evaluate the association between CCTA/FFR-CT versus ICA in patients with a CAC score > 399 and patient outcome as well as CAD progression with two years of follow-up.

This study is conducted in a pregraduate research year and consists of two sub studies:

1) Prognostic importance of fractional flow reserve derived from CT coronary angiography in patients with severe coronary calcifications and suspected stable coronary artery disease: a two year follow up study based on national registers

2) Non-invasive evaluation of progression of coronary artery disease by cardiac CT and fractional flow reserve derived from coronary computed tomography angiography in patients with severe coronary calcifications

Description of the cohort

The cohort comprise the patients enrolled in the FACC-study who provides informed consent to participate in this follow-up study and meets the inclusion - and exclusions criteria. 

The cohort consist of Danish men and women in the region of Southern Denmark with a CAC-score < 399. 

Inclusion criteria:

- Participation in FACC-study

Exclusion criteria; for renewed CCTA: 

- Previouscoronary revascularization including percutaneous coronary intervention (PCI) and bypass-surgery

- Impaired renal function (eGFR<40 ml/min/1.73m2)

- Pregnancy

- Contrast allergy

Data and biological material

Data collected for sub study 1 includes register data on diagnoses and procedures relating to cardiovascular disease and other adverse outcomes: 

- Myocardial infarction

- Coronary revascularization 

- Death from any cause

- Downstream testing for CAD: CCTA, ICA and/or myocardial perfusion imaging

Data collected for sub study 2 are renewed CCTA and FFR-CT for evaluation of progression of CAD and data from questionnaires sent to patients to evaluate progression of their symptoms.

Collaborating researchers and departments

Department of Cardiology, Odense University Hospital

• Assoc. professer Kristian Altern Øvrehus, MD, PhD

• Professor Hans Mickley, dr. med

• Professor, Axel Diederichsen, MD, PhD

Department of Cardiology, Odense University Hospital, Svendborg

• Jess Lambrecthsen, MD, PhD

Department of Cardiology, Lillebælt Hospital, Vejle

• Flemming Hald, ledende overlæge, MD

Department of Cardiology, Esbjerg Hospital

• Allan Rohold, specialeansvarlig overlæge, MD