Microvascular Resistance Reserve Assessment Derived from Absolute flow and Resistance by PET and CT

In at least 25% - 50% of patients with chest pain, myocardial ischemia can be
present without angiographic evidence of significant epicardial disease. In
such patients, it is often assumed that the microvasculature of the myocardium
is abnormal, called coronary microvascular dysfunction (CMD). This
microvascular dysfunction constitutes a diagnostic and therapeutic problem
with considerable morbidity and associated functional limitations, reduces
quality of life, impairs outcome, and increases economic burden for healthcare
systems. In the last years, a new invasive methodology has been developed for
true quantitative investigation of the coronary microcirculation by calculation
of the microvascular resistance reserve (MRR). Non-invasively, calculating the
MRR is also possible by measuring resting and hyperemic myocardial blood flow
(MBF), for example using quantitative Positron Emission Tomography (PET).
However, non-invasive MRR can only be calculated by PET alone in the complete
absence of any epicardial disease (i.e. a Fractional Flow Reserve [FFR] of
1.0). In order to obtain information on epicardial disease without using
invasive interrogation of the coronary arteries, a method has been developed by
HeartFlow Inc. to combine PET and FFR calculated from Coronary Computed
Tomography Angiography (FFRCT). Using this method, MRR can be calculated
non-invasively regardless of the presence of epicardial disease. However,
non-invasive MRR has never been validated against invasively measured MRR.

The main objective is to compare non-inavsive MRR, obtained using PET and FFRCT
(CT-scanning), with invasively measured MRR measurement using continuous
thermodilution.

This study is a prospective validation study in which all patients will undergo
dual energy CCTA and [15O]H2O PET scan before invasive coronary angiography
(ICA) in conjunction with invasive flow/pressure and thermodilution
measurements.

A three day protocol will be completed after referral ensuring the diagnostic
work-up of patients is not delayed. On day 1 patients will undergo CCTA. On day
2, patients will receive PET scan. Then, on day 3, irrespective of CCTA and PET
results, patients will undergo ICA with invasive pressure/thermodilution
measurements. The risks of CT and PET are considered to be low. Patients are
referred for a clinically indicated ICA and as such risks of the ICA are not
deemed study-related. The risk of invasive measurements during ICA are
considered low. No direct benefit is present for the participating patients.
Nevertheless, measurement of FFR, microvascular resistance and MRR is often
useful to make a better decision on performing or deferring PCI, is helpful to
better understand the nature of angina complaints in these patients, and
contributes to fine-tuning of medical treatment.