Identification of epicardial disease severity by FFR is partly obscured by the microvascular resistance, which illustrates the necessity of combined pressure and flow measurements in daily practice.

No abstract

Background-The assessment of functional coronary lesion severity using intracoronary physiological parameters such as coronary flow velocity reserve and the more widely used fractional flow reserve relies critically on the establishment of maximal hyperemia. We evaluated the diagnostic accuracy of the stenosis resistance index during nonhyperemic conditions, baseline stenosis resistance index, compared with established hyperemic intracoronary hemodynamic parameters, because achievement of hyperemia can be cumbersome in daily clinical practice. Methods and Results-A total of 228 patients, including 299 lesions (mean stenosis diameter 55%±11%), underwent myocardial perfusion scintigraphy for documentation of reversible perfusion defects. Distal coronary pressure and flow velocity were assessed with sensor-equipped guidewires during baseline and maximal hyperemia, induced by an intracoronary bolus of adenosine (20-40 μg). We determined stenosis resistance (SR) during baseline and hyperemic conditions as well as fractional flow reserve and coronary flow velocity reserve. The discriminative value for myocardial ischemia on myocardial perfusion scintigraphy of all parameters was compared using receiver-operating-characteristic curves. Baseline SR showed good agreement with myocardial perfusion scintigraphy.

BSR, iFR, and FFR have equivalent diagnostic accuracy for the detection of ischaemia-generating coronary stenoses.

Key points• The Valsalva manoeuvre provokes strong changes in the cardiovascular system and can be used to alter parameters of cardiac mechanics for studying cardiac-coronary interaction in humans.• Cardiac contraction results in coronary forward and backward travelling waves that can be quantified by wave intensity analysis.• Our results show that during a Valsalva manoeuvre, combined autoregulatory vasoconstriction and decreased extravascular compression contribute to an over-compensatory reduction in coronary microvascular resistance, which yields an essentially constant coronary flow velocity despite depressed cardiac performance.• The reduced energy of coronary waves during the Valsalva manoeuvre reflects the diminished compression of intramural vessels and thereby reduced extravascular resistance.• These findings help us better understand the mechanisms underlying cardiac-coronary interaction and are useful to validate physiological models of the coronary circulation being developed for patient-specific diagnostic support.Abstract Our aim was to investigate the effect of altered cardiac-coronary interaction during the Valsalva manoeuvre (VM) on coronary wave intensity and the response of coronary microvascular resistance. In 13 patients, left ventricular (P LV ) and aortic pressure were measured during catheterization, together with intracoronary pressure and blood flow velocity (U ) via a dual-sensor guide wire advanced into an angiographically normal coronary artery. Signals were analysed for the following phases of VM: baseline (B1), onset of strain (S1), sustained strain (S2), onset of release (R1), maximal response during recovery (R2), and baseline after VM. The immediate effects of VM were most evident from diastolic P LV (LVDP), which increased from 11.0 ± 2.3 to 36.4 ± 2.7 mmHg between B1 and S1 and fell from 28.3 ± 3.4 to 8.3 ± 1.9 mmHg between S2 and R1. Wave intensities and rate pressure product (RPP) were only minimally affected at these transient phases, but coronary wave energies decreased by about 50% and RPP by 38% from S1 to S2, together with a 30% depression of LVdP/dt. All signals were restored to baseline values during the recovery. U did not vary significantly throughout the VM. Despite the depressed cardiac performance during VM strain, microvascular resistance, calculated with LVDP as backpressure, decreased by 31% from B1 to S2, whereas an increase via metabolically induced vasoconstriction was expected. Since coronary U remained essentially constant despite the marked reduction in oxygen consumption, microvascular vasoconstriction must have been compensated by a decrease in the contraction-mediated impediment on coronary blood flow, as confirmed by the reduced coronary wave energies.

The increased risk of myocardial ischaemia in the presence of high HMR, uncorrected for collateral flow, demonstrates that HMR is reflective of an increase in actual MR, identifying pertinent pathophysiological alterations in the microvasculature.

With simultaneous pressure and flow velocity measurements, basal conditions do not systematically limit BSR accuracy compared with HSR. Consequently, diagnostic performance of BSR is equivalent to FFR, and closely approximates HSR.

We would like to thank the correspondents for their interest in our work.1 The debate on adenosine may well be an important factor hampering adoption of physiologically guided revascularization, and therefore the value of a vasodilator-free approach deserves consideration in the light of its possible clinical implications. However, we welcome the criticism employed by the correspondents, as we agree that a rise in adoption must not go hand-in-hand with a fall in accuracy. As such, although our results are favorable, baseline stenosis resistance index (BSR) is still in need of rigorous validation before the concept is of practical value in daily clinical practice.Although we have primarily evaluated the diagnostic accuracy of BSR for ischemia on an independent noninvasive reference standard, the conclusion of Michiels and colleagues that FFR determined in our study was suboptimal is important for the interpretation of our results. However, several aspects contrasting their conclusion need consideration. First, the rate of inaccurate FFR in our study is in accordance with other investigations reporting on this subject within a similarly heterogeneous patient population and noninvasive stress testing as a reference standard.2 Second, the use of low-dose (40 µg maximum) intracoronary adenosine has unequivocally been shown to equal intravenous (IV) (140 µg·kg -1 ·min -1 ) infusion in terms of FFR values.3 Third, all validation studies, evaluating the relation between FFR and myocardial ischemia on noninvasive stress testing, were performed using either low-dose intracoronary or IV adenosine. Both approaches yield equal optimal cut-off values averaging 0.74; a clear indication of their equality. Finally, the search for true maximal hyperemia has indicated that IV adenosine does not induce maximal hyperemia. 4 Hence, one may safely conclude that a direct relationship between FFR and myocardial ischemia is unequivocally determined for both low-dose intracoronary and IV adenosine, whereas neither achieves true maximal hyperemia. Therefore, FFR determined in our study can be considered accurate from a diagnostic point of view and a comparison between FFR and BSR valid.Indeed, the pressure gradient across a stenosis is flow-dependent. Importantly, the relation between this gradient and flow is unique for a given coronary stenosis geometry. This results in a unique and predictable course of this relationship from basal to hyperemic conditions. 5 Combining both pressure and flow information, BSR is a specific characteristic of the stenosis determined during basal conditions, with a high diagnostic accuracy for myocardial ischemia.1 Sen and colleagues interestingly raise the extent of flow velocity as an explanation for the difference in discriminative value between BSR and hyperemic stenosis resistance index. We believe that this difference arises from 2 factors that are indeed related to the extent of flow velocity. First, the presence of a measurement error, which unequivocally accompanies any measurement method, induces a...