Basal stenosis resistance index derived from simultaneous pressure and flow velocity measurements.

AIMS: Vasodilator-free basal stenosis resistance (BSR) equals fractional flow reserve (FFR) accuracy for ischaemia-inducing stenoses. Nonetheless, basal haemodynamic variability may impair BSR accuracy compared with hyperaemic stenosis resistance (HSR). We evaluated the influence of basal haemodynamic variability, as encountered in practice, on BSR accuracy versus HSR when derived from simultaneous pressure and flow velocity measurements, and determined its diagnostic performance for HSR-defined significant stenoses. METHODS AND RESULTS: Simultaneous coronary pressure and flow velocity were obtained in 131 stenoses. The impact of basal haemodynamic conditions on BSR was evaluated by means of their relationship with the relative difference between BSR and HSR. Diagnostic performance of BSR, FFR, iFR, and resting Pd/Pa was assessed by comparing the area under the curve (AUC), using HSR as reference standard. The relative difference between BSR and HSR was not associated with basal heart rate, aortic pressure or rate pressure product. Among all stenoses, as well as within the 0.6-0.9 FFR range, BSR AUC was significantly greater than resting Pd/Pa and iFR AUC; all other AUCs were equivalent. CONCLUSIONS: 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.

Head-to-head comparison of basal stenosis resistance index, instantaneous wave-free ratio, and fractional flow reserve: diagnostic accuracy for stenosis-specific myocardial ischaemia.

AIMS: We sought to compare the diagnostic accuracy of basal stenosis resistance index (BSR), instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) for stenosis-specific myocardial ischaemia identified by means of a combined reference standard of myocardial perfusion scintigraphy and the hyperaemic stenosis resistance index. METHODS AND RESULTS: BSR and FFR were determined for 299 coronary stenoses, iFR was determined for 85 coronary stenoses (iFR cohort). The discriminative value for stenosis-specific myocardial ischaemia was compared by means of the area under the receiver operating characteristic (ROC) curves (AUC). Classification agreement with the reference standard was determined according to ROC curve-derived ischaemic cut-off values, as well as according to clinical cut-off values, equivalent to the 0.80 FFR cut-off. Across all stenoses, the discriminative value of BSR and FFR was equivalent (AUC: 0.90 and 0.91, respectively, p=0.46). In the iFR cohort, the discriminative value was equivalent for BSR, iFR, and FFR (AUC: 0.88, 0.84, and 0.88, respectively; p≥0.20 for all). At both ischaemic as well as clinical cut-off values, classification agreement with the reference standard was equivalent for BSR and FFR across all stenoses, as well as for BSR, iFR, and FFR in the iFR cohort. CONCLUSIONS: BSR, iFR, and FFR have equivalent diagnostic accuracy for the detection of ischaemia-generating coronary stenoses.

Increased hyperaemic coronary microvascular resistance adds to the presence of myocardial ischaemia.

AIMS: It has been argued that hyperaemic microvascular resistance (HMR), defined as the ratio of mean distal coronary pressure to flow velocity, is overestimated in the presence of a coronary stenosis compared to actual microvascular resistance (MR), due to neglecting collateral flow. We aimed to test the hypothesis that HMR allows accurate identification of microvascular functional abnormalities by evaluating the association between high or low HMR and the presence of myocardial ischaemia on non-invasive stress testing. METHODS AND RESULTS: Myocardial perfusion scintigraphy was performed in 228 patients, with 299 lesions to identify reversible myocardial ischaemia. Intracoronary distal pressure and flow velocity were assessed during adenosine-induced hyperaemia (20-40 µg, intracoronary) to determine hyperaemic stenosis resistance (HSR) and HMR. HMR >1.9 mmHg/cm/s was defined as high. The diagnostic odds ratio (OR) for myocardial ischaemia for lesions associated with high compared to low HMR was 2.6 (95% confidence interval [CI]: 1.5-4.4; p<0.001) overall, 3.3 (95% CI: 1.2-9.0; p=0.02) for lesions with HSR >0.8 mmHg/cm/s, and 1.3 (95% CI: 0.6-2.9; p=0.52) for lesions with HSR ≤0.8 mmHg/cm/s. CONCLUSIONS: 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.

Impact of hyperaemic microvascular resistance on fractional flow reserve measurements in patients with stable coronary artery disease: insights from combined stenosis and microvascular resistance assessment.

BACKGROUND: Fractional flow reserve (FFR) aims to identify the extent of epicardial disease, but may be obscured by involvement of the coronary microvasculature. We documented the impact of hyperaemic stenosis resistance (HSR) and hyperaemic microvascular resistance (HMR) on FFR, and its relationship with myocardial ischaemia in patients with stable coronary artery disease. METHODS AND RESULTS: We evaluated 255 coronary arteries with stenoses of intermediate severity by means of intracoronary pressure and flow measurements to determine FFR, HSR and HMR. Myocardial perfusion scintigraphy (MPS) was performed to identify inducible myocardial ischaemia. In 178 patients, HMR was additionally determined in a reference coronary artery. Target vessel HMR was stratified according to reference vessel HMR tertiles. The diagnostic OR for inducible ischaemia on MPS of a positive compared with a negative FFR was significantly higher only in the presence of a high HMR (at the 0.75 and 0.80 FFR cut-off). Among stenoses with a positive FFR, the prevalence of ischaemia was significantly higher when HMR was high despite equivalent FFR across the HMR groups. This was paralleled by a concomitant significant increase in HSR with increasing HMR across groups. The relation between FFR and HSR (r(2)=0.54, p<0.001) was modulated by the magnitude of HMR, and improved substantially after adjustment for HMR (adjusted-r(2)=0.73, p<0.001), where, for epicardial disease of equivalent severity, FFR increased with increasing HMR. CONCLUSIONS: 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.

Functional coronary stenosis severity assessed from the mean pressure gradient-velocity relationship obtained by contrast medium-induced submaximal hyperaemia.

AIMS: First, to establish the diagnostic performance of the pressure gradient at a standardised mean velocity (dPv) as derived from the cycle-averaged stenosis pressure gradient-velocity (dP-v) relationship obtained by administration of adenosine and, second, to determine whether dPv can be assessed from contrast medium-induced submaximal hyperaemia. METHODS AND RESULTS: Distal coronary pressure and velocity were simultaneously recorded in 64 patients during the response to intracoronary injection of adenosine. dPv was assessed at velocities between 20 and 50 cm/s. The pressure gradient at a mean flow velocity of 30 cm/s (dPv30) yielded an excellent diagnostic performance against FFR ≤0.8 (area under the curve 0.96; sensitivity 84%; specificity 96%; accuracy 89%). In a subgroup of 21 patients, measurements were repeated throughout contrast medium-induced reactive hyperaemia. Peak velocity and pressure gradient were lower compared to adenosine, but the course of the corresponding dP-v relationships coincided very well over the common velocity range, with no difference in dPv30. CONCLUSIONS: dPv30 reliably detects functionally significant coronary lesions. It derives from stenosis haemodynamics and can be obtained with submaximal hyperaemia, such as following injection of contrast medium, thereby obviating the maximal vasodilation by adenosine required for FFR or other established hyperaemic parameters of functional stenosis severity.

Myocardial perfusion distribution and coronary arterial pressure and flow signals: clinical relevance in relation to multiscale modeling, a review.

Coronary artery disease, CAD, is associated with both narrowing of the epicardial coronary arteries and microvascular disease, thereby limiting coronary flow and myocardial perfusion. CAD accounts for almost 2 million deaths within the European Union on an annual basis. In this paper, we review the physiological and pathophysiological processes underlying clinical decision making in coronary disease as well as the models for interpretation of the underlying physiological mechanisms. Presently, clinical decision making is based on non-invasive magnetic resonance imaging, MRI, of myocardial perfusion and invasive coronary hemodynamic measurements of coronary pressure and Doppler flow velocity signals obtained during catheterization. Within the euHeart project, several innovations have been developed and applied to improve diagnosis-based understanding of the underlying biophysical processes. Specifically, MRI perfusion data interpretation has been advanced by the gradientogram, a novel graphical representation of the spatiotemporal myocardial perfusion gradient. For hemodynamic data, functional indices of coronary stenosis severity that do not depend on maximal vasodilation are proposed and the Valsalva maneuver for indicating the extravascular resistance component of the coronary circulation has been introduced. Complementary to these advances, model innovation has been directed to the porous elastic model coupled to a one-dimensional model of the epicardial arteries. The importance of model development is related to the integration of information from different modalities, which in isolation often result in conflicting treatment recommendations.

Intracoronary hemodynamic effects of pressure-controlled intermittent coronary sinus occlusion (PICSO): results from the First-In-Man Prepare PICSO Study.

BACKGROUND: Myocardial reperfusion is frequently suboptimal after ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI). Using a balloon-tipped catheter positioned in the coronary sinus (CS), pressure-controlled intermittent coronary sinus occlusion (PICSO) results in an intermittent obstruction of coronary venous outflow of the left anterior descending artery (LAD), and may improve myocardial perfusion by augmenting redistribution of blood to the border zone of ischemic myocardium. We sought to document the intracoronary hemodynamic effects of PICSO during PCI. METHODS: We included 15 patients with stable angina scheduled for PCI of the LAD. Balloon occlusion of the LAD was performed twice, once with and once without PICSO and lasting maximally 3 minutes each, to document the effect of PICSO on CS pressure and LAD wedge pressure. RESULTS: Catheter delivery was successful in all patients. The study protocol could not be conducted in 5 patients due to initial calibration difficulties (n = 3), a pressure wire problem (n = 1), and a vagal response at the start of the procedure (n = 1). In the remaining 10 patients, CS occlusion caused a marked increase in mean CS pressure (4.1 ± 7.3 mmHg vs. 22.0 ± 12.6 mmHg; P < 0.001) and CS pulse pressure (4.3 ± 0.8 mmHg vs. 36.1 ± 6.3 mmHg; P < 0.001). Concomitantly, mean distal LAD wedge pressure and wedge pulse pressure increased (32.4 ± 12.2 mmHg vs. 35.5 ± 12.6 mmHg; P < 0.001 and 39.1 ± 27.2 mmHg vs. 45.9 ± 26.0 mmHg; P < 0.001, respectively). At 30 day follow-up, no device-related events occurred. CONCLUSIONS: PICSO safely augments CS pressure, thereby increasing LAD coronary wedge pressure. These findings support further evaluation of PICSO in the setting of STEMI.

Diagnostic accuracy of combined intracoronary pressure and flow velocity information during baseline conditions: adenosine-free assessment of functional coronary lesion severity.

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 232 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. The diagnostic performance of baseline SR (area under the curve, 0.77; 95% CI, 0.71-0.83) was as accurate as fractional flow reserve and coronary flow velocity reserve (area under the curve, 0.77; 95% CI, 0.71-0.83 and area under the curve, 0.75; 95% CI, 0.68-0.81 respectively; P>0.05 compared with baseline SR for both). However, hyperemic SR, combining both pressure and flow velocity information during hyperemia, was superior to all other parameters (area under the curve, 0.81; 95% CI, 0.76-0.87; P<0.05 compared with all other parameters). CONCLUSIONS: Combined pressure and flow velocity measurements during baseline conditions may provide a useful tool for functional lesion severity assessment without the need for potent vasodilators.

Coronary wave intensity during the Valsalva manoeuvre in humans reflects altered intramural vessel compression responsible for extravascular resistance.

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.

Coronary pressure-flow relations as basis for the understanding of coronary physiology.

Recent technological advancements in the area of intracoronary physiology, as well as non-invasive contrast perfusion imaging, allow to make clinical decisions with respect to percutaneous coronary interventions and to identify microcirculatory coronary pathophysiology. The basic characteristics of coronary hemodynamics, as described by pressure-flow relations in the normal and diseased heart, need to be understood for a proper interpretation of these physiological measurements. Especially the hyperemic coronary pressure-flow relation, as well as the influence of cardiac function on it, bears great clinical significance. The interaction of a coronary stenosis with the coronary pressure-flow relation can be understood from the stenosis pressure drop-flow velocity relationship. Based on these relationships the clinically applied concepts of coronary flow velocity reserve, fractional flow reserve, stenosis resistance and microvascular resistance are discussed. Attention is further paid to the heterogeneous nature of myocardial perfusion, the vulnerability of the subendocardium and the role of collateral flow on hyperemic coronary pressure-flow relations. This article is part of a Special Issue entitled "Coronary Blood Flow".

Effect of the Valsalva maneuver on cardiac-coronary interaction assessed by wave intensity analysis.

The Valsalva maneuver (VM) provokes strong changes in the cardiovascular system and is therefore well suited to study the cardiac-coronary interaction in humans. In 12 patients undergoing catheterization we simultaneously recorded aortic pressure, left ventricular pressure, and intracoronary pressure (Pd) and flow velocity (U) while the patients were performing a VM. Coronary wave intensity was calculated (dI = dP*dU) at characteristic phases of the VM and related to hemodynamic parameters of left ventricular (LV) performance. During the strain, blood pressure increased transiently followed by a significant decrease (p < 0.001) at maximum strain. Changes in mean LV pressure followed the same pattern, while LV end-diastolic pressure increased to almost 40 mmHg (p < 0.001), with a 30% reduction in LV dP/dt (p < 0.005). Coronary flow velocity remained fairly constant throughout the VM. All hemodynamic values returned to the baseline at conclusion of the maneuver. Coronary wave intensity was strongly reduced during the strain and was related to the depression in LV performance. Wave intensity analysis clearly revealed the inherent features of cardiac-coronary interaction.