Reserve: Setting Criteria and Changing Clinical Practice
||Fractional flow reserve (FFR) is
the ratio of distal to proximal pressure on either side of a stenosis
during maximum hyperemia. The pressure sensor is located at
the junction of the radio-opaque and radiolucent segments of an
intracoronary guidewire, 3 cm proximal to the tip. Normal FFR is 1.0.
Provocable ischemia occurs with an FFR <0.75. Rest ischemia is present
with an FFR <0.2. While an FFR >0.75 typically correlates with a
negative stress test (exercise, thallium scintigraphy, or dobutamine
echocardiography), Dr. DeBruyne noted that there is a gray area when the
FFR measures 0.72-0.82.
||FFR may be especially useful in
patients with angiographic stenoses and atypical symptoms and/or in those
with no, nondiagnostic, or negative noninvasive test findings. In the
DEFER Study, 325 patients were enrolled. Those with an FFR <0.75
underwent intervention. Those with an FFR >0.75 were randomly assigned
to intervention or no intervention. At 1 year, the event-free survival
rates in the 3 groups were 81%, 75%, and 89%, respectively.
||FFR may also be useful in
patients with ambiguous left main disease. In one study, 30 patients had
an FFR <0.75 and underwent surgery; 24 had an FFR >0.75. At 29
months' follow-up, event-free survival was 83% and 79%, respectively.
||Thus, FFR is stenosis-specific,
takes collaterals into account, is applicable in multivessel disease, and
is independent of prevailing hemodynamics.
||Assessment of Endothelial
Function: Relieving Angina Without PCI The normal coronary artery responds
to acetylcholine with vasodilation. Early atherosclerosis, as well as the
presence of diabetes mellitus, hypertension, and hyperlipidemia cause
vasoconstriction. This is not just a laboratory finding; the
frequency of coronary events varies with the presence of endothelial
dysfunction. When patients are separated into thirds according to
endothelial function, those with the worst endothelial function have the
highest event rate (14%).
||Hyperlipidemia is an important
cause of endothelial dysfunction. Oxidized low-density lipoprotein (LDL --
especially small, dense LDL particles) activates macrophages, causes
inflammation, increases the adhesiveness of monocytes, and upregulates
procoagulant markers. These pathophysiologic findings are reversed with
lipid-lowering agents, especially in combination with antioxidants. These
pathophysiologic findings are even acutely reversible with lipopheresis.
||While routine assessment of
coronary endothelial dysfunction is not practical, brachial reactivity
(B-mode ultrasound assessment of brachial diameter artery response to cuff
occlusion) is a useful noninvasive surrogate. In the presence of normal
coronary endothelial function, the brachial artery diameter should
increase by 14%. In the presence of angiographically normal coronary
arteries but coronary endothelial dysfunction, the brachial artery
diameter increases by 9%. It falls to 4% in the presence of angiographic
CAD. Brachial reactivity is also abnormal in the presence of increasing
numbers of risk factors.
||The failure of
endothelial-dependent vasodilation as well as the presence of
procoagulants, macrophage infiltration, inflammation, and proliferation
can be reversed by aggressive risk factor modification -- especially
reducing LDL to <100 mg/dL and systolic blood pressure to <138 mm
Hg. This should be the goal in all patients with CAD, including those