How to define the hemodynamic significance of an equivocal iliofemoral artery stenosis: Review of literature and outcomes of an international questionnaire

Abstract

Purpose

The goal of the study was to review current literature regarding the diagnosis of equivocal (50–70%) iliofemoral artery stenosis and compare these findings with the daily practice of an international panel of endovascular experts.

Methods

The Medline Database was searched for relevant publications, and an electronic survey was sent to experts in the field covering the following topics: definition of an equivocal iliofemoral artery stenosis, angiographic visualization and investigation protocols of an equivocal stenosis, intra-arterial pressure measurements, and definition of hemodynamic significance of an equivocal iliofemoral artery stenosis using a physiologic measure.

Results

Of the 37 invited endovascular experts, 21 (53.8%) agreed to participate in the survey. Analysis of existing literature shows that the level of evidence for diagnosing equivocal iliofemoral artery stenosis is mediocre and is not being implemented by experts in the field.

Conclusion

Studies have shown that a stenosis of between 50% and 70% iliofemoral lumen diameter reduction shows a wide range of trans-stenotic pressure gradients. Equivocal iliofemoral artery stenosis can best be identified using three-dimensional quantitative vascular analysis software. Although evidence for a clear hemodynamic cutoff point is weak, performing trans-lesion intra-arterial pressure measurements at rest and during maximal hyperemia is preferred. Diagnosing iliofemoral artery stenosis solely on lumen diameter reduction is inadequate.

Keywords

Peripheral arterial occlusive disease iliofemoral artery stenosis diagnosis equivocal stenosis hemodynamic significance pressure measurements

Introduction

Atherosclerotic stenoses in the lower extremity arteries may cause intermittent claudication or critical limb ischemia (CLI) in 19.8% of men and 16.8% of women aged >65 years, although most people remain asymptomatic.¹ Progression of claudication or CLI may lead to serious complications such as tissue loss, amputation, and even death.¹ During the last decades, the number of iliofemoral percutaneous endovascular interventions has increased considerably compared with bypass surgery^2,3 because surgery is associated with higher mortality and morbidity rates and requires a longer hospital stay.⁴

Accurate diagnosis and treatment of iliofemoral arterial stenoses (IAS) is important to achieve optimal long-term outcomes. Although the initial success rate of iliac and femoral percutaneous transluminal angioplasty (PTA) procedures exceeds 90%, the 5-year patency rate is reported to be 71% (range 64–75%) for iliac arteries and 55% (range 52–62%) for femoropopliteal arteries.⁵ In-hospital complication rates of 3.5–9.2% have been reported.^6–8 Unnecessary angiographies and PTAs should be avoided by using noninvasive imaging to precisely determine the hemodynamic significance of the stenosis.

Currently, noninvasive imaging modalities—duplex ultrasound (DUS), magnetic resonance angiography (MRA), and computed tomography angiography (CTA)—are used to screen patients with intermittent claudication and CLI.^9–13 Reported sensitivity and specificity rates of these modalities are, respectively, 80% and 95% for DUS,^11,13 93% and 94% for MRA,^9–11 and 96% and 94% for CTA.^10,12 DUS, MRA, and CTA are sufficient to identify symptomatic high-grade stenoses (>75%) or occlusions that require treatment on one hand and asymptomatic nonsignificant stenoses (<30%) that do not need intervention on the other hand. Ideally, the decision to intervene on an IAS should be made noninvasively to avoid unnecessary invasive diagnostics and interventions. However, a large number of patients have equivocal stenoses or multilevel iliofemoral disease. Predicting the hemodynamic significance of these lesions, based on the current available noninvasive modalities, is difficult but important, especially because unnecessary treatment of hemodynamic nonsignificant stenoses may lead to complications, result in higher costs, and is unlikely to contribute to clinical improvement.¹⁴ However, an equivocal stenosis that is misinterpreted as hemodynamically insignificant may lead to undertreatment of a patient with a low quality of life.

In daily vascular practice, most interventionalists will treat any iliofemoral obstruction in patients with critical limb ischemia. On the other hand, the majority of patients with mild claudication can be treated with supervised exercise therapy alone. The main focus of this study includes patients with disabling claudication who do not respond to supervised exercise therapy with a single or multiple borderline (50–70%) stenoses. To date, little is known about the optimal diagnosis of iliacofemoral equivocal stenoses. This in contrast with coronary artery disease, where fractional flow reserve (FFR) is the most important physiological measure to determine the hemodynamic significance of a stenosis.^15,16 The objective of this study was to review literature and gather the results of a survey given to international endovascular experts with regard to this subject.

Materials and methods

Study design

This study reviewed the current literature regarding the diagnosis of equivocal IAS and compared this with the daily practice of an international panel of endovascular experts. An electronic survey, covering various items associated with equivocal IAS, was sent to these experts to determine their approach. Literature and survey outcomes were combined and discussed per item.

Literature search

The Medline database was searched for relevant publications using the following search terms: equivocal (or) ambiguous (or) dubious (or) borderline (or) critical (or) blood pressure determination* (MeSH) (or) pressure gradient (or) peripheral fractional flow reserve (pFFR) all in combination with (and) arterial occlusive diseases (MeSH) (or) stenosis (or) stenotic. Searches were performed without date or language restriction.

Electronic survey

An electronic questionnaire including 106 questions and statements was designed. Questions were based on the available endovascular literature. Experts of the FOundER group¹⁷ complemented by personal acquaintanced leading physicians, were invited to participate in filling out the survey. None of the individuals who were involved in designing the questionnaire participated in filling out the questionnaire and none of the experts who were invited to participate in filling out the survey were involved in writing any of the reviewed literature. All questions presented in the survey are about iliac and femoropopliteal arterial segments in patient with symptomatic and disabling claudication. The electronic survey covered the following main topics: definition of an iliofemoral equivocal stenosis in terms of lumen diameter reduction, angiographic visualization and investigation protocols of an equivocal stenosis, intra-arterial pressure measurements, and definition of hemodynamic significance of an equivocal IAS using a physiological measure.

Results

Of the 37 invited endovascular experts, 21 (53.8%) agreed to participate in the survey, and all submitted surveys were completely filled out. The panel consisted of 13 vascular surgeons (3 USA, 10 Europe), 5 interventional radiologists (1 Australia, 4 Europe), 2 interventional angiologists (2 Europe), and 1 interventional cardiologist (1 Europe). Endovascular experiences of the participants ranged from 8 to 25 years, with at least 50 iliac and femoropopliteal arterial endovascular procedures every year.

Definition of an equivocal stenosis

Literature

Historically, investigators interchanged the terms “reduction in lumen area” and “reduction in lumen diameter” to define stenosis. It should be noted that a lumen area reduction (A) of 70% is not equal to a 70% lumen diameter (d) reduction because lumen diameter is quadratic related to lumen area by the formula: $A = \frac{1}{4} π d^{2}$ (Figure 1). We chose to report stenosis as lumen diameter reduction, similar to the literature and daily practice.

Figure 1.

Lumen area reduction is plotted against lumen diameter reduction showing the quadratic relation. As indicated by the dashed lines, a lumen diameter reduction of 50–70% corresponds to a lumen area reduction of 75–90%.

Lumen diameter reduction, leading to a decrease in distal pressure or a reduction in blood flow, is historically termed “critical arterial stenosis.”"¹⁸ It is well known from theoretical and in vitro experiments that stenoses with <50% lumen diameter reduction will have a minimal influence on the flow and pressure drop.^19–21 These studies also show that in cases of >50% lumen diameter reduction, the translesion pressure drop rises quickly, depending on the amount of flow through the stenosed lumen. Wylie and coworkers²² observed that at least 70% of the lumen diameter had to be reduced before blood flow at rest was decreased.

Experimental, animal, and in vivo studies have shown that a stenosis between 50% and 70% lumen diameter reduction may lead to a wide range of pressure drops.^{19,20,23–26} This implies that a translesion pressure gradient is influenced not only by the percentage of lumen diameter reduction but also by other patient-specific properties such as stenosis length, arterial wall stiffness, flow profile (e.g. laminar or turbulent), and the presence of collateral vessels.²⁷ This underlines that a “critical arterial stenosis” is not a fixed lumen diameter reduction but is rather a range that depends on various patient-specific properties that may cause the stenosis to be hemodynamically significant.

Survey

All 21 experts indicated that they classify the stenosis by lumen diameter reduction, and 4 also would use lumen area reduction, if available. When experts were asked to indicate the range of an equivocal stenotic lesion, the lower and upper limits were 30% and 75% diameter reductions, respectively (Figure 2).

Figure 2.

The circles and squares indicate the lower and upper cutoff of an equivocal stenosis as indicated by the experts, respectively. The mean and two standard deviations are indicated for both cutoffs.

The literature findings and results from the questionnaire both underline that there is a certain range in the amount of lumen diameter reduction when an equivocal stenosis is evaluated.

Angiographic visualization and diagnoses of an equivocal stenosis

Literature

Single-plane angiography provides the physician with two-dimensional (2D) morphologic information. Depending on the orientation of the artery and a possible asymmetric shape of the plaque, this information can be misleading and will underestimate or overestimate the extent of the disease.²⁸ Therefore, single-plane angiography is unreliable to determine the true arterial stenosis rate.^29,30 Although a second oblique angiographic projection increases the radiation dose, it improves detection of stenosis and allows for better quantification of the extent of disease.^31–34 Grading peripheral stenosis is historically done by visual inspection of digitally subtracted angiographic images. However, eyeballing tends to underestimate <50% stenoses and to overestimate >50% stenoses.^35,36 Use of quantitative methods (e.g. vascular analysis software) reduces measurement bias by minimizing interobserver and intraobserver variation^35,37–39 and will lead to a more accurate assessment of true diameter reduction. For short vessel segments, 2D quantitative vascular analysis (QVA) gives an accurate estimation of the lumen diameter on a single 2D projection (Figure 3), whereas the use of three-dimensional (3D) QVA software yields an accurate estimation of the length, volume reduction of the lumen, and tortuosity of the target artery.⁴⁰ Accurate quantification is important for optimal diagnosis, treatment, and use of appropriate equipment (diameter of PTA balloons, stents, etc.).

Figure 3.

QVA (CAAS 5.9, PIE Medical, Maastricht, The Netherlands) of two common iliac artery stenoses both with ±50% area reduction. Both stenoses were visually inspected and expected to be non-significant. In both cases, intra-arterial pressure gradients were performed. For patient A, pressure gradients at rest and during drug induced hyperemia were 1.1 mmHg and 5.2 mmHg respectively, and for patient B gradients were 2.2 mmHg and 18.5 mmHg, respectively.

From a hemodynamic standpoint, the amount of pressure drop over a stenosis depends on other patient-specific properties rather than on lumen diameter reduction alone.^23–27 This is confirmed by a poor to moderate association between visual inspection of a stenosis on angiography and invasive pressure measurements at rest and during administration of vasodilators (r = 0.02–0.17; κ = 0.41–0.68).^41–44 Therefore, after identifying an equivocal stenosis by accurate estimation of the lumen diameter reduction, a physiological measure will be necessary to determine its hemodynamic significance. Guidelines recommend in vivo intra-arterial measurement of trans-lesion pressure gradients to determine the hemodynamic significance of an equivocal stenosis.^45,46 This is confirmed by Udoff and coworkers,²⁶ who showed that trans-lesion pressure gradients over a stenosis with a lumen diameter reduction of 50–75% exhibit a wide range of pressure gradients.

Survey

When noninvasive imaging (CTA, MRA, or DUS) suggests a single equivocal stenosis in a symptomatic patient, experts indicated they would use one angiographic view (4%), two (orthogonal) angiographic views (86%), or a rotational angiography (10%) to visualize and determine the severity of the lesion (Figure 4(a)).

Figure 4.

(a) What experts do when confronted with a single, equivocal stenosis on angiography. (b) How experts grade a single, equivocal stenosis on angiography. (c) How experts proceed after identifying a single, equivocal stenosis on angiography.

Subsequently, stenosis grading is done by visual inspection (76%), 2D QVA (19%), or 3D QVA (5%). Two of five experts use 2D or 3D QVA to perform manual segmentation (Figure 4(b)).

When a single equivocal stenosis was identified, four experts indicated that they would not treat the lesion, four experts indicated that they would treat the stenosis solely based on the lumen area reduction, and one expert would use additional intravascular ultrasound imaging to grade the stenosis accurately and to assess the complexity of the lesion, being well aware that no physiological information is provided. Another four experts indicated that they would decide to treat the stenosis based on the clinical context or DUS characteristics. Only eight experts indicated they would perform intra-arterial pressure measurements to diagnose the hemodynamic significance of an equivocal stenosis (Figure 4(c)).

Visualization of an equivocal stenosis requires optimal angiographic information and quantitative analysis to grade this stenosis. Intra-arterial pressure or flow measurements are necessary to determine clinical significance. Owing to the extensiveness of these measurements, they are not routinely used by most experts in the field.

Intra-arterial pressure measurements

Literature

Measuring a trans-lesion pressure gradient by using a standard 4F or 5F diagnostic catheter is a straightforward and nonexpensive way to assess the hemodynamic significance of a peripheral stenosis. However, it is important to realize that passing a diagnostic catheter across a stenosis will occupy space in the already reduced lumen area. Numerical and in vitro studies in silicon tubes with a lumen diameter of 8 mm have shown that the use of diagnostic catheters increases peak systolic pressure and alters the pressure waveform.⁴⁷ Especially in equivocal lesions of the IAS, this may lead to an elevated pressure drop mimicking a significant stenosis^48,49 and lead to an unnecessary intervention of a hemodynamic nonsignificant stenosis. Insertion of a 0.014-inch pressure wire through a stenosis occupies significantly less space, does not affect the pressure waveform, and will provide a more accurate estimation of the actual transstenotic pressure gradient.⁴⁷ These measurements have been shown to be reliable and reproducible,⁵⁰ are routinely used in the diagnosis of coronary artery disease,^15,16 and are considered to be the gold standard.⁵¹

In equivocal stenosis, blood flow at rest might be normal, which explains the absence of clinical symptoms (e.g. normal ankle-brachial index).^17,51 As a consequence, there is no or only a small pressure gradient present at rest. During exercise, peripheral resistance is lowered to increase flow and to satisfy the oxygen demand. As a consequence of the increased flow, the pressure drop aggravates over the equivocal stenosis,^19,25 as is commonly seen during the ankle-brachial index after exercise. To reproduce these physiological conditions during angiography, it is important to perform pressure measurements under hyperemic conditions using a vasodilator.^13,45,46 Castaneda-Zuniga and coworkers⁵² measured intra-arterial pressure gradients and reported a significant gradient increase after the injection of 30 mg of papaverine.

Tolazoline, papaverine, and nitroglycerine all act quickly (∼30 s) and have a short period of inducing peak hyperemia.⁵³ To obtain an accurate gradient, simultaneously measuring pressures proximally and distally of the stenosis is preferred, rather than performing a pullback maneuver, to eliminate fluctuations in blood pressure during the time needed to pullback the catheter.^25,26

Survey

Thirteen experts indicated that they do not perform trans-lesion intra-arterial pressure measurements. The eight experts who perform trans-lesion intra-arterial pressure measurements would perform a pullback maneuver rather than simultaneous proximal and distal pressure measurements. To perform this measurement, 4F (50%) or 5F (50%) catheters were used. Only two experts indicated that pressure gradients may be influenced by material choice and would therefore select materials based on artery size. Pressure measurements are mostly performed in rest (7 of 8 experts). Only one expert indicated performing measurements at rest and during medically induced hyperemia by administering 30 mg of papaverine.

When questioned why some experts do not use a 0.014-inch pressure wire to perform pressure measurements, three reasons were given: (1) the cumbersome nature of the measurement, especially using a vasodilator; (2) DUS imaging gives a better representation of local hemodynamics than an invasive pressure gradient; and (3) costs are often not reimbursed by health insurance companies.

Performing intra-arterial pressure measurements requires knowledge about the association between pressure and flow and the use of optimal materials, because both can influence outcome significantly when pressure gradients are measured over an equivocal stenosis.

Definition of a hemodynamically significant stenosis

Literature

In recent decades, various cutoff values for trans-lesion peak systolic pressure gradients and mean arterial pressure (MAP) gradients have been suggested as a functional measure to identify a hemodynamically significant stenosis.^25,54 The MAP gradient seems to be a good indicator because average flow depends on the peripheral resistance and is driven by the MAP; conversely, high flow rates present during systole might represent the most sensitive measure for the hemodynamic significance of a stenosis.^41,55 However, one major drawback is that systolic pressure gradients are influenced by vessel tapering and sudden changes in vessel elasticity (e.g. local calcifications).^56,57 Recent studies have demonstrated an association between the peak systolic velocity ratio (PSVR) and the pFFR, which is defined as the ratio of time-averaged distal pressure divided by time-averaged proximal pressure.^56–58 Table 1 provides an overview of the studies that have attempted to establish a cutoff value for a hemodynamic IAS.

Table 1.

Overview of studies reporting a cutoff value for a hemodynamic significant stenosis.

Author	Sample Size	Measure	Value	Drawbacks
Haimovici (1956)⁵⁹	13	FBI	1.03–1.27 (mean 1.14)	Rest, Large distance between measurements
Weismann (1963)⁵⁵	21	%ΔFBI	20%	Rest, Large distance between measurements
Wesolowski (1966)⁵⁴	41	Aortofemoral systolic gradient	10 mmHg	Rest
Sako (1966)⁶⁰	126	%ΔRHR	10–20%	LDV, not reported whether mean or systolic gradient is used
Moore (1971)³⁰	28	Femoral-femoral mean gradient	9 mmHg	No translesional measurement
Brener (1974)⁶³	98	Systolic %ΔRHR	15%	No translesional measurement
Quin (1975)⁶¹	20	systolic %ΔRHR	18%	No translesional measurement
Castaneda-Zuniga (1976)⁵²	16	Aortofemoral gradient	18.8 mmHg	Not reported whether mean or systolic gradient is used
Kaufman (1979)⁵³	-	Aortofemoral systolic gradient	20 mmHg	Experimental animal study
Udoff (1979)²⁶	42	Aortofemoral systolic gradient	20 mmHg
Brewster (1979)⁶⁵	150 (retrospective)	Aorto or brachial -femoral systolic gradient	15 mmHg	Reactive hyperemia
Barber (1980)⁶²	64(Prospective)	%ΔRHR	18%	No translesional measurement, not reported whether mean or systolic gradient is used
Flanigan (1984)⁶⁴	106 (Prospective)	%ΔFBI	15%	Large distance between measurements
Klein (2006)⁶⁶	279 (RCT)	Mean gradient	10 mmHg
Murata (2015)⁵⁸	23 (Retrospective)	pFFR	0.85

RCT: randomized controlled trial; %ΔFBI: femoral-brachial pressure index, and the maximum change in this index; %ΔRHR: resting-to-hyperemic ratio; Rest: measurements performed at rest and without the use of a vasodilator; LDV: Low dose vasodilator used, unable to induce maximal hyperemia; pFFR: peripheral fractional flow reserve.

A few studies focused on the hemodynamic significance of peripheral artery stenosis without the use of a vasodilator.^54,55,59 Sako and coworkers⁶⁰ first reported pressure measurements with induced hyperemia by administering 15 mg of papaverine. Although a vasodilator was used, the dosage administered was too low to induce maximal hyperemia. For optimal diagnosis, maximal hyperemia is crucial, and failing to achieve this (due to an inadequate dose or to using reactive hyperemia) will lead to insufficient results.⁵³

Other studies used percentage change in the rest-to-hyperemic ratio^60–63 or compared femoral pressures of both legs³⁰ rather than measurement of the trans-lesion pressure gradient. The decrease in femoral pressures observed during hyperemia is not only caused by increased flow over the stenosis but is also influenced by possible changes in systemic pressure due to administration of the vasodilator, which makes the use of these ratios less reliable.

Some studies used the femoral-brachial index,^{55,59,63–65} but owing to the large distance between the measurements, this index is suitable to define the extent of the disease rather than to grade a single equivocal stenosis and is not optimal from a procedural standpoint. It requires invasive measurements of both the brachial and femoral pressures that may lead to a prolonged procedure time, higher radiation dose, and increased risk of complications.

Udoff and coworkers²⁶ measured systolic pressure gradients in rest and during hyperemia in 42 patients (50 limbs). They showed that <50% stenoses were associated with hyperemic systolic pressure gradients <20 mmHg, whereas >75% stenoses had pressure gradients of >20 mmHg.²⁶ Interestingly, 50–75% stenoses showed a wide range of systolic pressure gradients.

In 2006, the Dutch Iliac Stent Trial (DIST) randomly compared primary stent placement with selective stent placement after PTA in 279 patients and showed noninferiority for selective stent placement. Patients were selectively stented when the residual mean pressure gradient was >10 mmHg.^66,67 Selective stent placement was proven to be a cost-effective method,^14,68 because only 40% of the patients needed actual stent placement after PTA.⁶⁶

Recently, Murata and coworkers⁵⁸ retrospectively included 22 patients (23 lesions) with intermediate stenosis (<75%). The pFFR was measured after injection of 250 µg of isosorbide dinitrate. The optimal cutoff value to identify a hemodynamically significant stenosis (defined as PSVR >2.5) was 0.85, with an area under the curve of 0.72, a sensitivity of 94%, and a specificity of 50%.

Survey

The prior mentioned eight experts, who measure pressure gradient across an equivocal stenosis, were asked to indicate the mean and systolic arterial pressure gradients that would define a hemodynamically significant equivocal stenosis (Figure 5). Two experts use the MAP, four experts use systolic pressure gradients, and two experts use both gradients. When considering MAP, experts indicated a cutoff value for hemodynamic significance varying between 15 and 40 mmHg. When considering systolic pressure gradients, experts use cutoff values varying between 10 and 50 mmHg.

Figure 5.

Mean and systolic pressure gradient considered by experts as indications for hemodynamically significant equivocal stenosis. *Of mean and systolic pressure gradient, according to the expert, this measure was considered the more important cutoff measure. †This expert performed measurements at rest and after administration of papaverine.

Discussion

Analysis of existing literature shows that the level of evidence regarding the diagnosis of equivocal iliofemoral stenoses is mediocre and does not serve as a real guidance for daily vascular practice. The definition and diagnosis of an equivocal iliofemoral stenosis remains one of the major challenges in the treatment of iliofemoral arterial obstructive disease. The absence of a cutoff value for hemodynamic significance of IAS stenosis leads to various approaches and different treatment strategies. It is of great importance that endovascular specialists are aware of the pitfalls and the physiologic variables concerning the diagnosis of an equivocal stenosis. Moreover, the interventionalists should understand the basics of underlying hemodynamics and should get acquainted with the added value of trans-stenotic pressure gradients.

The decision to perform an angiography will remain unchanged and will be based on a combination of patient complaints, ABI, walking distance and non-invasive imaging modalities (duplex ultrasound, MRA or CTA). However, in case of angiography and doubt about the hemodynamic significance of a stenosis, a physiological measure should be used to guide diagnosis and intervention. A stenosis between 50% and 70% lumen diameter reduction shows a wide range of pressure gradients depending on other patient-specific parameters rather than on lumen diameter reduction alone. Neither visual inspection^41–44 by experts nor noninvasive quantitative vascular analysis methods can predict whether equivocal stenotic lesions are hemodynamically significant.⁶⁹

Intra-arterial transstenotic pressure measurements are currently considered to be the gold standard to quantify the hemodynamic significance of a stenosis^45,46 and should be performed liberally, because noninvasive methods are not precise enough. Other studies have suggested the use of a femoral-brachial index,^{55,59,63–65} but owing to the large distance between the sites of both measurements, the authors believe femoral-brachial indexes are more suited to defining the extent of disease rather than to grading a single equivocal stenosis.

Unfortunately, when encountering an equivocal stenosis, most experts do not perform pressure measurements in daily practice owing to the cumbersome nature of the hyperemic measurements and the additional cost not reimbursed by the health insurance companies. This can also be explained by one of the following reasons:

First, in treating and diagnosing peripheral arterial occlusive disease, there is only mediocre evidence concerning cutoff values to grade an equivocal stenosis. Available studies remain unclear whether an intervention should be guided by a mean pressure gradient of 10 mmHg or a systolic pressure gradient of 20 mmHg, and even the evidence regarding these chosen values is slim, which is reflected by the large spread on the cutoff values used by the experts. The DIST used a mean pressure gradient of 10 mmHg as cutoff point for selective stent placement after PTA and is the only available randomized trial to show favorable symptomatic outcome when treating lesions with a mean pressure gradient of >10 mmHg. The introduction of pFFR looks promising, but will need further research to determine an optimal cutoff in the lower extremity.^57,58 In coronary artery disease (CAD), FFR is the gold standard for determining the hemodynamic significance of a coronary artery stenosis and has proven to optimize diagnosis and clinical outcome.^15,16

Second, although the administration of a vasodilator is known to result in a higher pressure drop than reactive hyperemia,⁵³ knowledge is still lacking about potential vasodilators that can be used to induce maximal hyperemia over an IAS. The lack of knowledge of the effect on peripheral blood flow after the intra-arterial administration of these vasodilators hampers optimal diagnosis of equivocal IAS. Therefore, dose–response studies and comparison between these potential vasodilators are required to optimize peripheral pressure measurements.

Limitations

The study is limited by a response rate of 53.8%. Unfortunately, multiple reminders to the invited participants did not increase the response rate. Therefore, a selection bias cannot be excluded.

The survey was designed by physicians and engineers with a good understanding of the hemodynamic behaviour of blood flow around a stenosis and with extensive experience in performing in-vivo hemodynamic measurements. It is recognized that experts, perhaps even some who participated in the survey, could be inexperienced with intra-arterial pressure measurements.

Another limitation of this study is the fact that the panellists represented different specialities and countries with very different models of health care which may influence the outcomes of this questionnaire.

Conclusions

Studies have shown that a stenosis between 50% and 70% lumen diameter reduction causes a wide range in pressure gradient, which underlines that a “critical arterial stenosis” is not a fixed lumen diameter reduction. Rather, it is a range of diameter reductions that might cause an equivocal stenosis to be hemodynamic significant when combined with other patient-specific cardiovascular properties. Although extendedly researched in the past, evidence for a clear hemodynamic cutoff point is weak and often based on small case series or animal studies.

In case of doubt, the hemodynamic significance of an equivocal stenosis (50–70%) can best be determined by performing trans-lesion intra-arterial pressure measurements in rest and during maximal hyperemia. Currently, the best evidence for identifying a hemodynamically significant stenosis is a time-averaged trans-lesional pressure gradient of 10 mmHg or a systolic pressure gradient of 20 mmHg. Diagnosis, solely based on grading diameter or lumen area reduction alone, will not suffice.

Footnotes

Acknowledgements

The authors would like to acknowledge the participants of the survey: Jos C. van den Berg, Colin Bicknell, Marianne Brodmann, Frank Criado, Lukas van Dijk, Eric Ducasse, Roberto Ferraresi, Peter Goverde, Isabelle van Herzeele, Andrew Holden, Sumaira Macdonald, Geert Maleux, Erich Minar, Vincent Riambau, Sonia Ronchey, Marc Schermerhorn, Darren Schneider, Carlo Setacci, Jörg Tessarek, Frank Vermassen, and Fabio Verzini.

Authors’ contribution

SWB and SGHH contributed equally to this work.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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