Fractional Flow Reserve

Technique or Treatment

FFR is obtained as part of diagnostic cardiac catheterization. A guide catheter is utilized to advance the FFR-specific guide wire to the coronary artery orifice. At which point, a coronary artery pressure proximal to the stenotic lesion (or Pa) is obtained. The operator (or interventional cardiologist) then advances the FFR-specific guide wire and crosses the intermediate stenotic lesion allowing for coronary artery pressure distal to the stenosis (or Pd) to be obtained. The pressure sensor can be visualized angiographically by the operator, to help ensure proper placement.

FFR measurements must be obtained during a period of maximal blood flow or maximal hyperemia. To achieve maximal hyperemia, a hyperemic stimulus is administered either intravenously or intracoronary through the guide catheter, FFR is monitored for a period of 3 to 4 minutes. Intravenous (IV) adenosine is the most widely used method to induce maximal hyperemia.[9][10]

Equation

FFR is defined as the ratio of maximum achievable blood flow through a blockage (area of stenosis) to the maximum achievable blood flow in the same vessel in the hypothetical absence of the blockage. It is calculated using a pressure ratio of pressure measured distal to the blockage (Pd) and pressure proximal to the blockage (Pa).

The ‘‘normal’’ ratio is expected to be 1. For example, an FFR value of 0.80 means that the maximum blood flow in the coronary artery being measured is 80% of what it would be if the artery were completely normal.

FFR = Pd / Pa

• Pd = pressure distal to the lesion (blockage)
• Pa = pressure proximal to the lesion (blockage)

Interpretation

In utilizing FFR, coronary stenosis can be classified into three groups based on physiologic assessment during coronary angiography:

FFR Measurement/Treatment

• Ischemia-producing stenosis (FFR less than 0.75)/Revascularization
• Non–ischemia-producing stenosis (FFR greater than 0.80)/Medical Therapy
• Gray zone (FFR 0.75 to 0.80)/Revascularization versus Medical therapy

Clinical Significance

Coronary artery disease (CAD) is one of the leading causes of death in the United States, accounting for 1 out of every 4 deaths annually. Coronary revascularization has long been a definitive treatment for reducing symptoms, myocardial infarction and death in acute coronary syndromes (ACS). However, coronary revascularization is not as clear in stable CAD.

One of the major setbacks with coronary revascularization has been the dependence on angiographic (or visual estimation) analysis of lesions. During angiography, a number of factors are considered which will ultimately dictate the best treatment course. These include the patient’s symptoms, clinical characteristics, an angiographic appearance of the coronary anatomy, and alternative options, which may include CABG. This leaves a large area of operator variability with regards to interpretation and treatment. This lack of clarity has led to inappropriate stenting cases, which have been well publicized. This focus has drawn attention from media, providers, clinicians, and payors to develop criteria and guidelines, standardizing the process of coronary revascularization.

Some trials have been published, helping to establish the Appropriate Use Criteria (AUC) for coronary revascularization. The AUC is the good intent to ensure that the right procedure is performed on the right patient at the right time for the right reasons, to achieve the best possible outcome. Reliance on clinical trials, guidelines, and AUC serve as the framework upon which coronary revascularization is performed.

The development of FFR arose in the early 1990s as a means of selecting physiologically significant lesions. The DEFER (2001) trial was the first major landmark trial, showcasing FFR and demonstrating coronary revascularization could be safely deferred when lesions had an FFR greater than 0.75. However, FFR was not widely used in subsequent years for a variety of reasons.

The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE, 2007) studied PCI in patients with stable CAD and high-grade coronary stenosis, randomizing patients to PCI versus optimal medical therapy. The COURAGE trial failed to demonstrate the benefit with routine revascularization of coronary lesions when compared to optimal medical therapy alone. This landmark trial along with inappropriate stenting and further establishment of AUC and guidelines brought FFR back to the forefront.

Enhancing Healthcare Team Outcomes

The Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME, 2009) compared patients undergoing routine PCI for stable multivessel CAD to either FFR-guided or angiography-guided PCI with both groups being on OMT. FAME (2009) demonstrated that FFR was superior to traditional angiography-guided PCI among patients with stable multivessel CAD demonstrating lower 1-year adverse events and reduced costs. This trial paved the way for continued study and evaluation of FFR capability when compared to OMT, as demonstrated in the COURAGE (2007) trial. Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME 2, 2011) studied the role of PCI among patients with stable single or multivessel CAD with physiologically significant coronary lesions. In contrast to FAME, FAME 2 focused on patients with FFR less than or equal to 0.80, comparing PCI to OMT alone. Among patients with stable CAD with FFR less than or equal to 0.80, PCI demonstrated overall better outcomes with regards to death, nonfatal MI, and urgent revascularization.

The preponderance of clinical trial evidence for FFR driven revascularization prompted incorporation of FFR into the 2011 American College of Cardiology (ACC)/American Heart Association (AHA) and 2014 European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Guidelines.