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Assessment of individual stenoses in tandem lesions or diffusely diseased vessels – an unmet clinical need

In unobstructed vessels, flow during hyperemia can be many fold higher than that observed during rest. In the presence of a single stenosis, resting flow is typically maintained while hyperemic flow diminishes for any stenosis > 40–50% in anatomical severity ( Fig. 1 , upper panel) . It was this finding in animals that lead to the concept that stenoses > 50% are haemodynamically important. Since for practical reasons we are typically reliant upon pressure measurements rather than flow measurements, then understanding pressure-flow relationships is essential.

The expected behaviour of hyperemic and resting flow after removal of stenosis.

Upper panel. Pioneering studies demonstrated that resting flow is preserved until stenoses are critical or subtotally occluded. Hyperemic flow falls in the presence of any stenosis but does so significantly as stenoses exceed 40-50%.

Lower panel. In Tandem stenoses (A), a measurement of flow at the black marker (•) will elicit a flow value as denoted by the black dot on the upper panel. In (B), the distal stenosis has been stented. Under hyperemic conditions, flow will have increased significantly (red dot); however, under resting conditions, there is minimal change expected.

The degree of pressure drop across a stenosis is dependent upon the (1) stenosis severity and (2) the amount flow across it. Using flow velocity as a surrogate for volumetric flow, this relationship between stenosis pressure gradient and flow can be measured to yield a specific fingerprint of the stenosis; with each single stenosis having a specific haemodynamic signature as originally described by Gould .

In the situation of a vessel with two tandem lesions, hyperemic flow across the proximal lesion is a function not only of the stenosis geometry but also the effect of the second, distal lesion. Similarly hyperemic flow across the second lesion is a function of its specific geometry and its inlet flow, which is influenced by the proximal stenosis ( Fig. 2 ). As a result, a pressure assessment in the distal vessel under ‘maximal hyperaemia’ will not be specific to either stenosis, rather it informs us of the haemodynamic impact of all the disease in the entire vessel. If surgical revascularisation is being considered, where a graft is positioned distally, then this may be helpful information. However, it is not possible to determine an accurate FFR for each individual stenosis. Due to the sensitivity of hyperaemic flow to the presence of proximal or distal disease, a measurement of FFR between two tandem stenoses will differ from that measured after one of the stenoses is treated. Therefore, placing the pressure wire between tandem stenoses to attempt to understand the flow limitation caused by the proximal stenosis can be misleading . This is because the presence of the distal stenosis means the increase in flow caused by the hyperaemic agent is not transmitted uniformly though the vessel; as a result the measured pressure distal to the proximal stenosis may be higher than may actually be the case, causing the severity of the proximal stenosis to be underestimated. The removal of the distal stenosis by intervention will increase hyperaemic flow and thereby change the pressure ratio across the residual stenoses ( Fig. 1 ). To overcome this haemodynamic interaction between stenoses and determine an accurate FFR for the residual stenosis, the second lesion must be treated and physiological assessment must then be repeated.

Tandem stenoses cause flow interaction under hyperemic conditions.

The presence of two or more stenoses creates complex interaction of flow and thereby impacts upon pressure measurements. Formulae are available to estimate the FFR of a given stenosis without the impact of another but requires balloon occlusion of the stenosis in question (Pw).

Complex formulae have been derived in an attempt to try and overcome these difficulties but are difficult to apply in the catheter laboratory ( Fig. 2 ) . They require a commitment to ballooning one of the stenoses for determination of wedge pressure and when there is uncertainty over stenoses, an interventionalist would prefer to avoid vessel trauma. A more practical solution to circumvent this limitation is the process of performing multiple hyperaemic measurements whist pulling the pressure wire back along the length of the artery. This aims to demonstrate where in the vessel the greatest steps in pressure gradient are present. It does not overcome the issue of stenosis interaction but can be used to help a cardiologist decide which lesion is likely to be causing most of the pressure loss. Such an approach only offers a crude estimate of the severity of each stenosis and the issue remains that, after stenting, the pattern of flow in the vessel will change, rendering the initial assessment of any residual stenosis inaccurate. Therefore such gradients cannot not predict coronary haemodynamics post-PCI .

These difficulties imposed by hyperemia has hindered the development of predictive systems that can model the physiological result of stenting in the presence of multiple lesions . As a result this is currently not possible in clinical practice. A modality that can facilitate stenosis specific assessment would add significant value in the management of these patients. Potentially it may permit tailoring of the stenting strategy to optimise physiological outcome.

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Baseline physiology provides a potential solution to tandem lesion assessment

A potential solution for the assessment of tandem lesions is to use the unique characteristics of baseline physiology. Auto-regulatory mechanisms ensure resting flow is stable and changes little regardless of stenosis severity . The distal microcirculatory bed, a key governor of coronary flow, dilates under resting conditions to maintain resting flow even when severe epicardial artery narrowings are present . Whilst flow is maintained, this is at the expense of resting distal coronary pressure. The dilation of the microcirculation causes distal pressure to fall, generating a pressure gradient that is essential to maintain coronary flow. It is this pressure gradient that is detected by modern high fidelity pressure wires, permitting stenosis assessment under basal conditions .

Whilst baseline flow is maintained constant until almost subtotal occlusion of the vessel, hyperaemic flow changes dramatically according to the presence or absence of distal and proximal disease ( Fig. 2 ). This means that the basal state is uniquely suited to the assessment of vessels with diffuse or tandem lesions; because basal flow across the lesion of interest is expected to be negligibly affected by other lesions in the vessel ( Fig. 1 ) provided they are not critical or subtotal occlusions. Even if there is some interaction under resting conditions at a given point, the interaction is expected to be very small and much less than that seen under hyperemia.

This minimal interaction between the stenoses means that a given trans-stenotic pressure ratio measured at a particular point in a vessel is less likely to be affected by other stenoses within the vessel. Similarly, the haemodynamic assessment of the stenosis would not be affected when another stenosis in the vessel is treated by stenting, since the nature of resting flow suggests that there would be minimal change in resting flow after stenting typical stenoses. This allows several assessments of the coronary artery that are clinically useful, such as:

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  Evaluation of the stenosis burden of the complete vessel; providing a cumulative assessment of all stenoses in that territory. This is also currently possible with hyperaemic measures.

  
  
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  Quantification of the impact of individual stenoses within a diffusely diseased vessel or a vessel with tandem stenoses; permitting the differentiation of stenoses according to their magnitude of contribution to the overall disease burden of the vessel – impossible with current hyperaemic measures.

  
  
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  Prediction of the physiological effect of treating a particular stenosis within the vessel; permitting intervention according to the likely physiological gain. This is not possible with current hyperaemic measures but is particularly advantageous for diffusely diseased vessels as it may prevent the clinician from embarking on a revascularisation strategy that may improve the appearance of the vessel but not improve the blood flow to the subtended territory.

Resting flow therefore offers unique properties that may overcome the difficulties seen during hyperaemia. A pressure wire pullback under basal conditions may therefore offer an innovation to improve physiological assessment in vessels with diffuse or tandem coronary disease by providing stenosis specific information. For such an innovation to be readily applicable to day-to-day practice, the approach must be simple, glean the most information from the basal haemodynamics, easy to perform and be done using routinely available pressure wires.