The following discussion describes two clinical trials (FORECAST and FUSION) at the University of California at San Francisco Medical Center which examine the accuracy of the myocardial fractional flow reserve (FFRmyo) in determining the hemodynamic severity of a coronary artery stenosis.

Background:
Stress thallium scintigraphy is a well-accepted method of identifying the hemodynamic significance of coronary lesions. It is not uncommon to find intermediate-grade coronary stenoses during coronary angiography. Intravascular ultrasound is one technique performed in the cardiac catheterization laboratory which can help determine whether an intermediate coronary lesion is or is not functionally significant. Another emerging technique under active investigation is calculating the myocardial fractional flow reserve (FFRmyo) using a guidewire which can measure a pressure gradient across a coronary lesion.

The PressureWire:
The PressureWire (Radi Medical Systems) is a 0.014 inch guidewire with a mounted pressure sensor. This guide wire is used for high-fidelity pressure measurements in the coronay arteries. It allows the physiologic assessment of coronary lesions in the catheterization laboratory utilizing a pressure-derived index of lesion severity, the so-called FFRmyo.

Calculating FFRmyo:
FFRmyo measures the ratio between the pressure distal to a lesion (guide wire) to the pressure proximal to a lesion (guiding catheter) under adenosine-induced hyperemia. The carefully validated equation has a clear cut-off of 0.75, with a ratio of less than 0.75 identifying a functionally significant stenosis.

Case Examples of FFRmyo: The following 2 examples illustrate how the FFRmyo can be used in clinical practice:

Example 1: After crossing a lesion in the left anterior descending coronary artery, the mean pressures in the aorta (Pa) and distal to the stenosis (Pd) are 100 mmHg and 50 mmHg respectively. The ratio Pd / Pa equals 50 / 100 mmHg = 0.50. This lesion is hemodynamically significant and no further injection of adenosine is required.

Example 2: After crossing a lesion in the left anterior descending coronary artery, the mean pressures in the aorta (Pa) and distal to the stenosis (Pd) are 100 mmHg and 98 mmHg respectively. The ratio Pd / Pa equals 98 / 100 mmHg = 0.98. After induction of hyperemia by intracoronary injection of 24 mcg of adenosine, the mean pressures in the aorta (Pa) and distal to the stenosis (Pd) are 100 mmHg and 68 mmHg respectively. The ratio Pd / Pa measures 68 / 100 mmHg = 0.68. This is below the cut-off value of 0.75 and indicates a functionally significant stenosis.

FORECAST: FORECAST is a multicenter trial aimed at comparing the accuracy of stress thallium scintigraphy and FFRmyo as a means of determining the functional significance of a coronary stenosis. Drs. Morton Kern (St. Louis Medical Center) and Paul Yock (Stanford University Medical Center) are the principal investigators for the trial.

The FORECAST study will enroll 50 patients with stable angina who are referred to the cardiac catheterization laboratory with abnormal stress thallium scintigraphic studies. To be eligible, coronary angiography must show single-vessel coronary disease with one coronary lesion of 50-80% diameter stenosis and less than 20 mm in length. Following informed written consent, the FFRmyo determination with the PressureWire will be performed prior to and immediately following percutaneous coronary intervention (PCI). A repeat stress thallium study will be performed 1-2 weeks following the coronary intervention. Clinical endpoints will be recorded after one month.

Additional exclusion criteria include unstable or rest angina, myocardial infarction within one month, electrocardiographic evidence of Q waves in leads corresponding to the target vessel territory, any patient with a contraindication to emergent bypass surgery, acute or chronic renal insufficiency (creatinine >1.3), and a left ventricular ejection fraction <30%.

FUSION: A similar study called the Fractional Flow Reserve and Ultrasound Indices for Objective Narrowing Assessment (FUSION) is also being performed. Drs. Kern and Yock are also the principal investigators for this trial. This study will compare the accuracy of FFRmyo and intravascular ultrasound (IVUS) in determining the function significance of an intermediate coronary lesion.

To be enrolled in FUSION, patients are not required to have a thallium study. Additionally, patients with multivessel coronary artery disease can be enrolled in FUSION. The protocol for FUSION requires that FFRmyo and IVUS is performed prior to and immediately following PCI. Clinical endpoints will be recorded after one month.

Who to Contact: If you have any questions, feel free to contact
Andrew D. Michaels (UCSF Co-Director of the Cath Lab; 415-514-2104)