Transtenotic coronary flow velocity assessment: a new road map for non-invasive coronary evaluation?

About 40 years ago, K. Lance Gould proposed the concept of coronary flow reserve (CFR) to quantify the effect of epicardial narrowings on myocardial blood flow reserve in animal models,¹ experiments that still constitute the basis of our understanding of coronary physiology. The development of flow velocity catheters,^2,3 progress in positron emission tomography-derived absolute flow measurements,⁴ and, more recently, transthoracic Doppler flow velocity measurements⁴ extended Gould's findings into patients with coronary artery disease. Until the development of the concept of fractional flow reserve,^4,5 CFR was the only index commonly used in the clinical field, enabling us/doctors/practitioners to quantify flow limitation due to a plaque. Yet the main problem with CFR in clinical practice resides in its lack of specificity for the epicardial vessel: an excessively low CFR value does not determine whether this abnormal flow velocity relates to epicardial stenosis, to microvascular disease, or to a combination of both. In addition, the cut-off value for separating normal from abnormal is actually a moving target and is influenced by a large variety of factors such as blood pressure, heart rate, resting flow (which is difficult to obtain in a patient in a catheterization or echocardiography laboratory), myocardial mass, and age. To overcome these limitations, ∼10 years ago, Pijls introduced fractional flow reserve (FFR) into the Cath-lab as a new parameter, one that is generated from the ratio of transtenotic pressure differences between the proximal and distal and acts as a very good predictor of outcomes in ischaemic patients.^6,7 A few years ago, a new index of coronary stenosis called iFR was introduced into the Cath-Lab. This differs from FFR, because it is based on instantaneous ratio of transtenotic wave intensity analysis, extrapolated in a precise cardiac cycle just after the onset of diastole, where a balance between pressure waves from the aorta and microcirculation is produced, the so-called wave-free period, with the advantages of avoiding the use of drugs such as adenosine.⁸ In last two decades, the possibility of assessing a significant tract of the left anterior coronary artery has been introduced into the Echo-Lab through the possibility of assessing adequately flow and flow velocity reserve with transthoracic ultrasound.⁹ This extraordinary new opportunity of evaluating a coronary flow functionally and non-invasively had a great impact on patient outcomes.^9,10 Starting from this pathophysiological concept, Dr Holte et al.¹¹ has published an interesting non-invasive experience on the assessment of coronary disease, highlighting a new parameter that represents the expression of transstenotic flow velocity and seems to be a good predictor of coronary artery narrowing. These authors combined findings of pSPVR ≥2.0 and mosaic flow at Nyquist limit ≥0.48 m/s; the sensitivity and specificity of demonstrating significant stenoses in the LM, LAD, Cx, and RCA were 75 and 98%, 74 and 95%, 40 and 87%, and 34 and 98%, respectively. This means that these innovative parameters act well for LAD but less so for the other coronary arteries. Another important finding was that peak SPVR did not differ significantly between coronary arteries with reduced and normal CFVR, with a cut-off of CFVR <2.0. Furthermore, demonstrating a local coronary flow acceleration and turbulence on TTE non-invasively may become an attractive approach for the identification of significant stenoses without pharmacological provocation, either by comparing stenotic and prestenotic flow velocities or finding local mosaic flow at a substantially elevated velocity range.^12,13 Similar results in terms of a potential diagnostic role of an increased flow velocity on LAD were highlighted by Moreo, who found an excellent statistical relationship between coronary flow velocity of >0.7 m/s and the presence of a critical lesion on the left anterior descending coronary artery.¹⁴ This finding is also remarkable from a pathophysiological point of view, because myocardial autoregulatory mechanisms maintain blood flow at the cost of a pressure gradient that may represent the trigger for a number of physical forces potentially contributing to plaque destabilization: turbulence, abnormal shear stress, high and localized plaque stress, slicing forces and torsion, and intraplaque gradients. As a result, this finding may have added value not just from a diagnostic point of view but above all as a predictor of worsening ischaemic events. Nevertheless, while its confirmation of its role as a prognostic marker is awaited from larger trial studies, this innovative parameter for quantifying coronary flow velocity could, at least on the left anterior descending coronary artery, offer important information from a clinical practice standpoint, by potentially providing a fast and reliable, non-invasive, functional coronary investigation capable of guiding the correct management of patients suspected of having coronary disease. It could therefore represent a new road map in non-invasive ultrasound coronary investigation.