Influence of hemodynamic conditions on fractional flow reserve: parametric analysis of underlying model

Pressure-based fractional flow reserve (FFR) is used clinically to evaluate the functional severity of a coronary stenosis, by predicting relative maximal coronary flow (Q(s)/Q(n)). It is considered to be independent of hemodynamic conditions, which seems unlikely because stenosis resistance is flow dependent. Using a resistive model of an epicardial stenosis (0-80% diameter reduction) in series with the coronary microcirculation at maximal vasodilation, we evaluated FFR for changes in coronary microvascular resistance (R(cor) = 0.2-0.6 mmHg. ml(-1). min), aortic pressure (P(a) = 70-130 mmHg), and coronary outflow pressure (P(b) = 0-15 mmHg). For a given stenosis, FFR increased with decreasing P(a) or increasing R(cor). The sensitivity of FFR to these hemodynamic changes was highest for stenoses of intermediate severity. For P(b) > 0, FFR progressively exceeded Q(s)/Q(n) with increasing stenosis severity unless P(b) was included in the calculation of FFR. Although the P(b)-corrected FFR equaled Q(s)/Q(n) for a given stenosis, both parameters remained equally dependent on hemodynamic conditions, through their direct relationship to both stenosis and coronary resistance.     

Assessment of collateral artery function and growth in a pig model of stepwise coronary occlusion

Therapeutic stimulation of collateral artery growth is a promising approach for treatment of cardiovascular diseases. Unfortunately, translation into clinical practice yet remains cumbersome. Cardiovascular physiology and anatomy are major determinants of vascular growth processes. Hence, large-animal models are needed to improve clinical translatability of preclinical research. Furthermore, acute complete occlusions are mostly applied in experimental research, whereas stepwise occlusions are more often observed in human disease. We developed a model of coronary collateral artery growth in which 1) the artery is occluded in a step wise approach, and 2) effects of local treatment can be measured individually for each supplying coronary vessel. A hemodynamically relevant stenosis was created by implantation of a tapered stent at day 0 (d0) in the left circumflex artery (LCX), followed by complete arterial occlusion at day 14 (d14). Fluorescent microspheres were injected for demarcation of perfusion territories at each time point. Three and four weeks after induction of stenosis, collateral conductance measurements were performed for each coronary artery separately using differently labeled fluorescent microspheres. Postmortem angiography after acute LCX occlusion confirmed the presence of preexistent coronary anastomoses in the pig. The tapered stent created a hemodynamically significant stenosis immediately postplacement (fractional flow reserve, 0.70 ± 0.03). Between day 21 and 28, collateral conductance significantly increased in both the left anterior descending (LAD) and the right coronary artery (RCA)-supplied, collateral-dependent territories (LAD d21, 0.77 ± 0.14; LAD d28, 1.35 ± 0.12; RCA d21, 0.88 ± 0.29; RCA d28, 1.70 ± 0.16 ml · min(-1) · g(-1) · 100 mmHg(-1)), indicating collateral artery growth. We here describe a new translational minimally invasive model of coronary collateral artery growth in pigs, according to a defined protocol of LCX-stenosis and subsequent occlusion, allowing preclinical evaluation of arteriogenic therapies.     

Influence of coronary collateral flow on coronary diagnostic parameters: An in vitro study

Functional severity of coronary stenosis is often assessed using diagnostic parameters. These parameters are evaluated from the combined pressure and/or flow measurements taken at the site of the stenosis. However, when there are functional collaterals operating downstream to the stenosis, the coronary flow-rate increases, and the pressure in the stenosed artery is altered. This effect of downstream collaterals on different diagnostic parameters is studied using a physiological representative in vitro coronary flow-loop.The three diagnostic parameters tested are fractional flow reserve (FFR), lesion flow coefficient (LFC), and pressure drop coefficient (CDP). The latter two were discussed in recent publications by our group (Banerjee et al., 2008, Banerjee et al., 2007, 2009). They are evaluated for three different severities of stenosis and tested for possible misinterpretation in the presence of variable collateral flows. Pressure and flow are measured with and without downstream collaterals. The diagnostic parameters are then calculated from these readings.In the case of intermediate stenosis (80% area blockage), FFR and LFC increased from 0.74 to 0.77 and 0.58 to 0.62, respectively, for no collateral to fully developed collateral flow. Also, CDP decreased from 47 to 42 for no collateral to fully developed collateral flow. These changes in diagnostic parameters might lead to erroneous postponement of coronary intervention. Thus, variability in diagnostic parameters for the same stenosis might lead to misinterpretation of stenosis severity in the presence of operating downstream collaterals.     

Myocardial blood volume and coronary resistance during and after coronary angioplasty

Animal experiments have shown that the coronary circulation is pressure distensible, i.e., myocardial blood volume (MBV) increases with perfusion pressure. In humans, however, corresponding measurements are lacking so far. We sought to quantify parameters reflecting coronary distensibility such as MBV and coronary resistance (CR) during and after coronary angioplasty. Thirty patients with stable coronary artery disease underwent simultaneous coronary perfusion pressure assessment and myocardial contrast echocardiography (MCE) of 37 coronary arteries and their territories during and after angioplasty. MCE yielded MBV and myocardial blood flow (MBF; in ml · min(-1) · g(-1)). Complete data sets were obtained in 32 coronary arteries and their territories from 26 patients. During angioplasty, perfusion pressure, i.e., coronary occlusive pressure, and MBV varied between 9 and 57 mmHg (26.9 ± 11.9 mmHg) and between 1.2 and 14.5 ml/100 g (6.7 ± 3.7 ml/100 g), respectively. After successful angioplasty, perfusion pressure and MBV increased significantly (P < 0.001 for both) and varied between 64 and 118 mmHg (93.5 ± 12.8 mmHg) and between 3.7 and 17.3 ml/100 g (9.8 ± 3.4 ml/100 g), respectively. Mean MBF increased from 31 ± 20 ml · min(-1) · g(-1) during coronary occlusion, reflecting collateral flow, to 121 ± 33 ml · min(-1) · g(-1) (P < 0.01), whereas mean CR, i.e., the ratio of perfusion pressure and MBF, decreased by 20% (P < 0.001). In conclusion, the human coronary circulation is pressure distensible. MCE allows for the quantification of CR and MBV in humans.     

The diastolic flow velocity-pressure gradient relation and dpv50 to assess the hemodynamic significance of coronary stenoses

To evaluate the hemodynamic impact of coronary stenoses, the fractional (FFR) or coronary flow velocity reserve (CFVR) usually is measured. The combined measurement of instantaneous flow velocity and pressure gradient (v-dp relation) is rarely used in humans. We derived from the v-dp relation a new index, dp(v50) (pressure gradient at flow velocity of 50 cm/s), and compared the diagnostic performance of dp(v50), CFVR, and FFR. Before coronary angiography was performed, patients underwent noninvasive stress testing. In all coronary vessels with an intermediate or severe stenosis, the flow velocity, aortic, and distal coronary pressure were measured simultaneously with a Doppler and pressure guidewire after induction of hyperemia. After regression analysis of all middiastolic flow velocity and pressure gradient data, the dp(v50) was calculated. With the use of the results of noninvasive stress testing, the dp(v50) cutoff value was established at 22.4 mmHg. In 77 patients, 124 coronary vessels with a mean 39% (SD 19) diameter stenosis were analyzed. In 43 stenoses, ischemia was detected. We found a sensitivity, specificity, and accuracy of 56%, 86%, and 76% for CFVR; 77%, 99%, and 91% for FFR; and 95%, 95%, and 95% for dp(v50). To establish that dp(v50) is not dependent on maximal hyperemia, dp(v50) was recalculated after omission of the highest quartile of flow velocity data, showing a difference of 3%. We found that dp(v50) provided the highest sensitivity and accuracy compared with FFR and CFVR in the assessment of coronary stenoses. In contrast to CFVR and FFR, assessment of dp(v50) is not dependent on maximal hyperemia.     

Quantification of absolute coronary flow reserve and relative fractional flow reserve in a swine animal model using angiographic image data

Coronary flow reserve (CFR) and fractional flow reserve (FFR) are important physiological indexes for coronary disease. The purpose of this study was to validate the CFR and FFR measurement techniques using only angiographic image data. Fifteen swine were instrumented with an ultrasound flow probe on the left anterior descending artery (LAD). Microspheres were gradually injected into the LAD to create microvascular disruption. An occluder was used to produce stenosis. Contrast material injections were made into the left coronary artery during image acquisition. Volumetric blood flow from the flow probe (Q(q)) was continuously recorded. Angiography-based blood flow (Q(a)) was calculated by using a time-density curve based on the first-pass analysis technique. Flow probe-based CFR (CFR(q)) and angiography-based CFR (CFR(a)) were calculated as the ratio of hyperemic to baseline flow using Q(q) and Q(a), respectively. Relative angiographic FFR (relative FFR(a)) was calculated as the ratio of the normalized Q(a) in LAD to the left circumflex artery (LC(X)) during hyperemia. Flow probe-based FFR (FFR(q)) was measured from the ratio of hyperemic flow with and without disease. CFR(a) showed a strong correlation with the gold standard CFR(q) (CFR(a) = 0.91 CFR(q) + 0.30; r = 0.90; P < 0.0001). Relative FFR(a) correlated linearly with FFR(q) (relative FFR(a) = 0.86 FFR(q) + 0.05; r = 0.90; P < 0.0001). The quantification of CFR and relative FFR(a) using angiographic image data was validated in a swine model. This angiographic technique can potentially be used for coronary physiological assessment during routine cardiac catheterization.     

Evaluation of functional severity of coronary artery disease and fluid dynamics' influence on hemodynamic parameters: A review

Coronary Artery Disease (CAD) is responsible for most of the deaths in patients with cardiovascular diseases. Diagnostic coronary angiography analysis offers an anatomical knowledge of the severity of the stenosis. The functional or physiological significance is more valuable than the anatomical significance of CAD. Clinicians assess the functional severity of the stenosis by resorting to an invasive measurement of the pressure drop and flow. Hemodynamic parameters, such as pressure wire assessment fractional flow reserve (FFR) or Doppler wire assessment coronary flow reserve (CFR) are well-proven techniques to evaluate the physiological significance of the coronary artery stenosis in the cardiac catheterization laboratory. Between the two techniques mentioned above, the FFR is seen as a very useful index. The presence of guide wire reduces the coronary flow which causes the underestimation of pressure drop across the stenosis which leads to dilemma for the clinicians in the assessment of moderate stenosis. In such condition, the fundamental fluid mechanics is useful in the development of new functional severity parameters such as pressure drop coefficient and lesion flow coefficient. Since the flow takes place in a narrowed artery, the blood behaves as a non-Newtonian fluid. Computational fluid dynamics (CFD) allows a complete coronary flow simulation to study the relationship between the pressure and flow. This paper aims at explaining (i) diagnostic modalities for the evaluation of the CAD and valuable insights regarding FFR in the evaluation of the functional severity of the CAD (ii) the role of fluid dynamics in measuring the severity of CAD.     

Influence of heart rate on fractional flow reserve, pressure drop coefficient, and lesion flow coefficient for epicardial coronary stenosis in a porcine model

A limitation in the use of invasive coronary diagnostic indexes is that fluctuations in hemodynamic factors such as heart rate (HR), blood pressure, and contractility may alter resting or hyperemic flow measurements and may introduce uncertainties in the interpretation of these indexes. In this study, we focused on the effect of fluctuations in HR and area stenosis (AS) on diagnostic indexes. We hypothesized that the pressure drop coefficient (CDP(e), ratio of transstenotic pressure drop and distal dynamic pressure), lesion flow coefficient (LFC, square root of ratio of limiting value CDP and CDP at site of stenosis) derived from fluid dynamics principles, and fractional flow reserve (FFR, ratio of average distal and proximal pressures) are independent of HR and can significantly differentiate between the severity of stenosis. Cardiac catheterization was performed on 11 Yorkshire pigs. Simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual sensor-tipped guidewire for HR < 120 and HR > 120 beats/min, in the presence of epicardial coronary lesions of <50% AS and >50% AS. The mean values of FFR, CDP(e), and LFC were significantly different (P < 0.05) for lesions of <50% AS and >50% AS (0.88 ± 0.04, 0.76 ± 0.04; 62 ± 30, 151 ± 35, and 0.10 ± 0.02 and 0.16 ± 0.01, respectively). The mean values of FFR and CDP(e) were not significantly different (P > 0.05) for variable HR conditions of HR < 120 and HR > 120 beats/min (FFR, 0.81 ± 0.04 and 0.82 ± 0.04; and CDP(e), 95 ± 33 and 118 ± 36). The mean values of LFC do somewhat vary with HR (0.14 ± 0.01 and 0.12 ± 0.02). In conclusion, fluctuations in HR have no significant influence on the measured values of CDP(e) and FFR but have a marginal influence on the measured values of LFC. However, all three parameters can significantly differentiate between stenosis severities. These results suggest that the diagnostic parameters can be potentially used in a better assessment of coronary stenosis severity under a clinical setting.     

Characterizing momentum change and viscous loss of a hemodynamic endpoint in assessment of coronary lesions

Myocardial fractional flow reserve (FFR(myo)) and coronary flow reserve (CFR), measured with guidewire, and quantitative angiography (QA) are widely used in combination to distinguish ischemic from non-ischemic coronary stenoses. Recent studies have shown that simultaneous measurements of FFR(myo) and CFR are recommended to dissociate conduit epicardial coronary stenoses from distal resistance microvascular disease. In this study, a more comprehensive diagnostic parameter, named as lesion flow coefficient, c, is proposed. The coefficient, c, which accounts for mean pressure drop, Delta p, mean coronary flow, Q, and percentage area stenosis, can be used to assess the hemodynamic severity of a coronary artery stenoses. Importantly, the contribution of viscous loss and loss due to momentum change for several lesion sizes can be distinguished using c. FFR(myo), CFR and c were calculated for pre-angioplasty, intermediate and post-angioplasty epicardial lesions, without microvascular disease. While hyperemic c decreased from 0.65 for pre-angioplasty to 0.48 for post-angioplasty lesion with guidewire of size 0.35 mm, FFR(myo) increased from 0.52 to 0.87, and CFR increased from 1.72 to 3.45, respectively. Thus, reduced loss produced by momentum change due to lower percentage area stenosis decreased c. For post-angioplasty lesion, c decreased from 0.55 to 0.48 with the insertion of guidewire. Hence, increased viscous loss due to the presence of guidewire decreased c compared with a lesion without guidewire. Further, c showed a linear relationship with FFR(myo), CFR and percentage area stenosis for pre-angioplasty, intermediate and post-angioplasty lesion. These baseline values of c were developed from fluid dynamics fundamentals for focal lesions, and provided a single hemodynamic endpoint to evaluate coronary stenosis severity.     

Increased basal coronary blood flow as a cause of reduced coronary flow reserve in diabetic patients

A reduced coronary flow reserve (CFR) has been demonstrated in diabetes, but the underlying mechanisms are unknown. We assessed thermodilution-derived CFR after 5-min intravenous adenosine infusion through a pressure-temperature sensor-tipped wire in 30 coronary arteries without significant lumen reduction in 30 patients: 13 with and 17 without a history of diabetes. We determined CFR as the ratio of basal and hyperemic mean transit times (T(mn)); fractional flow reserve (FFR) as the ratio of distal and proximal pressures at maximal hyperemia to exclude local macrovascular disease; and an index of microvascular resistance (IMR) as the distal coronary pressure at maximal hyperemia divided by the inverse of the hyperemic T(mn). We also assessed insulin resistance by the homeostasis model assessment (HOMA) index. FFR was normal in all investigated arteries. CFR was significantly lower in diabetic vs. nondiabetic patients [median (interquartile range): 2.2 (1.4-3.2) vs. 4.1 (2.7-4.4); P = 0.02]. Basal T(mn) was lower in diabetic vs. nondiabetic subjects [median (interquartile range): 0.53 (0.25-0.71) vs. 0.64 (0.50-1.17); P = 0.04], while hyperemic T(mn) and IMR were similar. We found significant correlations at linear regression analysis between logCFR and the HOMA index (r(2) = 0.35; P = 0.0005) and between basal T(mn) and the HOMA index (r(2) = 0.44; P < 0.0001). In conclusion, compared with nondiabetic subjects, CFR is lower in patients with diabetes and epicardial coronary arteries free of severe stenosis, because of increased basal coronary flow, while hyperemic coronary flow is similar. Basal coronary flow relates to insulin resistance, suggesting a key role of cellular metabolism in the regulation of coronary blood flow.     

Effect of simultaneous intracoronary guidewires on the predictive accuracy of functional parameters of coronary lesion severity

The aim of this study was to assess the influence of a second guidewire on the diagnostic accuracy of functional parameters of coronary lesion severity. Sixty-five patients with intermediate coronary lesions underwent myocardial perfusion scintigraphy. Fractional flow reserve (FFR), coronary flow velocity reserve (CFVR), and hyperemic stenosis resistance (HSR) index (HSR = stenosis pressure gradient / velocity) were determined in 77 lesions. Distal pressure and velocity were acquired simultaneously (dual wire) and sequentially (single wire) with two sensor-equipped guidewires. Overall, functional parameters deteriorated from single- to dual-wire assessment. In patients without ischemia, the good diagnostic performance of FFR, CFVR, and HSR deteriorated significantly (P < 0.001) when assessed by dual wires, with an increase in the number of false-positive results. This trend was more pronounced for HSR, since the presence of a second wire reduced maximal velocity and increased the pressure gradient. The presence of two guidewires, especially across a myocardial perfusion scintigraphy-induced nonsignificant lesion, is associated with overestimation of the hemodynamically assessed lesion severity and, therefore, is likely to have a major impact on clinical decision making. This underscores the advantage of a dual-sensor-equipped guidewire for the evaluation of stenosis severity by combined pressure and velocity measurements.     

Residual angina pectoris after percutaneous coronary intervention for acute coronary syndrome

Fractional flow reserve (FFR) is an important diagnostic tool to guide decision-making in the cardiac catheterisation laboratory and for evaluation of percutaneous coronary interventions (PCI). Especially the pressure pullback curve at maximal hyperaemia is convincing in demonstrating the exact location and severity of a coronary stenosis. This pressure pullback curve can also demonstrate the presence of diffuse disease. We present a case in which FFR with pressure pullback curve seven days after a PCI, which did not result in complete symptom relief, indicates the presence of diffuse disease. Based on this result the patient was treated medically.     

Feasibility of coronary blood flow simulations using mid-fidelity numeric and geometric models

Biomechanics and Modeling in Mechanobiology - The fractional flow reserve index (FFR) is currently used as a gold standard to quantify coronary stenosis’s functional relevance. Due to its...     

Influence of zero flow pressure on fractional flow reserve

Fractional flow reserve (FFR) is a commonly used index to assess the functional severity of a coronary artery stenosis. It is conventionally calculated as the ratio of the pressure distal (P_d) and proximal (P_a) to the stenosis (FFR=P_d/P_a). We hypothesize that the presence of a zero flow pressure (P _zf), requires a modification of this equation. Using a dynamic hydraulic bench model of the coronary circulation, which allows one to incorporate an adjustable P _zf, we studied the relation between pressure-derived FFR=P_d/P_a, flow-derived true FFR_Q=Q_S/Q_N (=ratio of flow through a stenosed vessel to flow through a normal vessel), and the corrected pressure-derived FFR_C=(P_d–P_zf)/(P_a–P_zf) under physiological aortic pressures (70 mmHg, 90 mmHg, and 110 mmHg). Imposed P_zf values varied between 0 mmHg and 30 mmHg. FFR_C was in good agreement with FFR_Q, whereas FFR consistently overestimated FFR_Q. This overestimation increased when P_zf increased, or when P_a decreased, and could be as high as 56% (P_zf=30 mmHg and P_a=70 mmHg). According to our experimental study, calculating the corrected FFR_C instead of FFR, if P_zf is known, provides a physiologically more accurate evaluation of the functional severity of a coronary artery stenosis.     

Association between coronary lesion severity and distal microvascular resistance in patients with coronary artery disease

Homogeneity of microvascular resistance in different perfusion areas of the same heart is generally assumed. We investigated the effect of the severity of an epicardial stenosis on microvascular resistance in 27 patients with coronary artery disease and stable angina. All patients had an angiographically normal coronary artery, an artery with an intermediate lesion, and an artery with a severe lesion; the latter was treated with angioplasty. In each patient, distal blood flow velocity and pressure were measured during baseline and maximal hyperemia (induced by intracoronary adenosine) using a Doppler and pressure guide wire, respectively. The ratio of mean distal pressure to average peak blood flow velocity was used as an index for the microvascular resistance (MRv). Within patients, the hyperemic MRv was higher in arteries with more severe stenosis (P = 0.021). After percutaneous transluminal coronary angioplasty (PTCA), the hyperemic MRv decreased (pre-PTCA, 2.6 vs. post-PTCA, 1.9 mmHg.cm(-1)s(-1), P < 0.01) toward the value of the reference artery (1.7 mmHg.cm(-1)s(-1); P = 0.67). We conclude that there is a positive association between coronary lesion severity and variability of distal microvascular resistance that normalizes after angioplasty. This study challenges the concept of uniform distribution of hyperemic MRv that is relevant for the interpretation of both noninvasive and invasive diagnostic tests.     

Effect of heart rate on hemodynamic endpoints under concomitant microvascular disease in a porcine model

Diagnosis of the ischemic power of epicardial stenosis with concomitant microvascular disease (MVD) is challenging during coronary interventions, especially under variable hemodynamic factors like heart rate (HR). The goal of this study is to assess the influence of variable HR and percent area stenosis (%AS) in the presence of MVD on pressure drop coefficient (CDP; ratio of transstenotic pressure drop to the distal dynamic pressure) and lesion flow coefficient (LFC; ratio of %AS to the CDP at the throat region). We hypothesize that CDP and LFC are independent of HR. %AS and MVD were created using angioplasty balloons and 90-μm microspheres, respectively. Simultaneous measurements of pressure drop (DP) and velocity were done in 11 Yorkshire pigs. Fractional flow reserve (FFR), CDP, and LFC were calculated for the groups HR < 120 and HR > 120 beats/min, %AS < 50 and %AS > 50, and additionally for DP < 14 and DP > 14 mmHg, and analyzed using regression and ANOVA analysis. Regression analysis showed independence between HR and the FFR, CDP, and LFC while it showed dependence between %AS and the FFR, CDP, and LFC. In the ANOVA analysis, for the HR < 120 beats/min and HR > 120 beats/min groups, the values of FFR (0.82 ± 0.02 and 0.82 ± 0.02), CDP (83.15 ± 26.19 and 98.62 ± 26.04), and LFC (0.16 ± 0.03 and 0.15 ± 0.03) were not significantly different (P > 0.05). However, for %AS < 50 and %AS > 50, the FFR (0.89 ± 0.02 and 0.75 ± 0.02), CDP (35.97 ± 25.79.10 and 143.80 ± 25.41), and LFC (0.09 ± 0.03 and 0.22 ± 0.03) were significantly different (P < 0.05). A similar trend was observed between the DP groups. Under MVD conditions, FFR, CDP, and LFC were not significantly influenced by changes in HR, while they can significantly distinguish %AS and DP groups.     

Percutaneous Coronary Intervention Enhances Accelerative Wave Intensity in Coronary Arteries

Background

The systolic forward travelling compression wave (sFCW) and diastolic backward travelling decompression waves (dBEW) predominantly accelerate coronary blood flow. The effect of a coronary stenosis on the intensity of these waves in the distal vessel is unknown. We investigated the relationship between established physiological indices of hyperemic coronary flow and the intensity of the two major accelerative coronary waves identified by Coronary Wave Intensity analysis (CWIA).

Methodology / Principal Findings

Simultaneous intracoronary pressure and velocity measurement was performed during adenosine induced hyperemia in 17 patients with pressure / Doppler flow wires positioned distal to the target lesion. CWI profiles were generated from this data. Fractional Flow Reserve (FFR) and Coronary Flow Velocity Reserve (CFVR) were calculated concurrently. The intensity of the dBEW was significantly correlated with FFR (R = -0.70, P = 0.003) and CFVR (R = -0.73, P = 0.001). The intensity of the sFCW was also significantly correlated with baseline FFR (R = 0.71, p = 0.002) and CFVR (R = 0.59, P = 0.01). Stenting of the target lesion resulted in a median 178% (interquartile range 55–280%) (P<0.0001) increase in sFCW intensity and a median 117% (interquartile range 27–509%) (P = 0.001) increase in dBEW intensity. The increase in accelerative wave intensity following PCI was proportionate to the baseline FFR and CFVR, such that stenting of lesions associated with the greatest flow limitation (lowest FFR and CFVR) resulted in the largest increases in wave intensity.

Conclusions

Increasing ischemia severity is associated with proportionate reductions in cumulative intensity of both major accelerative coronary waves. Impaired diastolic microvascular decompression may represent a novel, important pathophysiologic mechanism driving the reduction in coronary blood flow in the setting of an epicardial stenosis.     

Windkesselness of coronary arteries hampers assessment of human coronary wave speed by single-point technique

A novel single-point technique to calculate local arterial wave speed (SPc) has recently been presented and applied in healthy human coronary arteries at baseline flow. We investigated its applicability for conditions commonly encountered in the catheterization laboratory. Intracoronary pressure (P(d)) and Doppler velocity (U) were recorded in 29 patients at rest and during adenosine-induced hyperemia in a distal segment of a normal reference vessel and downstream of a single stenosis before and after revascularization. Conduit vessel tone was minimized with nitroglycerin. Microvascular resistance (MR) and SPc were calculated from P(d) and U. In the reference vessel, SPc decreased from 21.5 m/s (SD 8.0) to 10.5 m/s (SD 4.1) after microvascular dilation (P < 0.0001). SPc was substantially higher in the presence of a proximal stenosis and decreased from 34.4 m/s (SD 18.2) at rest to 27.5 m/s (SD 13.4) during hyperemia (P < 0.0001), with a concomitant reduction in P(d) by 20 mmHg and MR by 55.4%. The stent placement further reduced hyperemic MR by 26% and increased P(d) by 26 mmHg but paradoxically decreased SPc to 13.1 m/s (SD 7.7) (P < 0.0001). Changes in SPc correlated strongly with changes in MR (P < 0.001) but were inversely related to changes in P(d) (P < 0.01). In conclusion, the single-point method yielded erroneous predictions of changes in coronary wave speed induced by a proximal stenosis and distal vasodilation and is therefore not appropriate for estimating local wave speed in coronary vessels. Our findings are well described by a lumped reservoir model reflecting the "windkesselness" of the coronary arteries.     

Increased diastolic time fraction as beneficial adjunct of alpha1-adrenergic receptor blockade after percutaneous coronary intervention

The effect of alpha1-receptor blockade with urapidil on coronary blood flow and left ventricular function has been attributed to relief of diffuse coronary vasoconstriction following percutaneous coronary intervention (PCI). We hypothesized that an increase in diastolic time fraction (DTF) contributes to the beneficial action of urapidil. In eleven patients with a 63% (SD 13) diameter stenosis, ECG, aortic pressure (Pa) and distal intracoronary pressure (Pd), and blood flow velocity were recorded at baseline and throughout adenosine-induced hyperemia. Measurements were obtained before and after PCI and after subsequent alpha1-receptor blockade with urapidil (10 mg ic). DTF was determined from the ECG and the Pa waveform. Functional parameters such as coronary flow velocity reserve, fractional flow reserve, and an index of hyperemic microvascular resistance (HMR) were assessed. Urapidil administration after PCI induced an upward shift in the DTF-heart rate relationship, resulting in a 3.1% (SD 2.7) increase in hyperemic DTF at a constant heart rate (P < 0.005) due to a shorter duration of systole. Hyperemic Pa and Pd decreased, respectively, by 6.1% (SD 6.6; P < 0.05) and 5.7% (SD 5.8; P < 0.01) after alpha1-blockade. Although epicardially measured functional parameters were on average not altered by alpha1-blockade due to concurrent changes in pressure and heart rate, HMR decreased by urapidil in those patients where coronary pressure remained constant. In conclusion, alpha1-receptor blockade after PCI produced a modest but significant prolongation of DTF at a given heart rate, thereby providing an adjunctive beneficial mechanism for improving subendocardial perfusion, which critically depends on DTF.     

Delineating the guide-wire flow obstruction effect in assessment of fractional flow reserve and coronary flow reserve measurements

Hemodynamic analysis was conducted to determine uncertainty in clinical measurements of coronary flow reserve (CFR) and fractional flow reserve (FFR) over pathophysiological conditions in a patient group with coronary artery disease during angioplasty. The vasodilation-distal perfusion pressure (CFR-p(rh)) curve was obtained for 0.35- and 0.46-mm guide wires. Our hypothesis is that a guide wire spanning the lesions elevates the pressure gradient and reduces the flow during hyperemic measurements. Maximal CFR-p(rh) was uniquely determined by the intersection of measured CFR and calculated p(rh) of native and residual epicardial lesions in patients without microvascular disease, during angioplasty. Extrapolation of the linear curve gave a zero-coronary flow mean pressure (p(zf)) of approximately 20 mmHg and a corresponding p(rh) of 55 mmHg in the native lesions, which coincided with the level that causes ischemia in human hearts. On this linear curve, values of CFR and FFRmyo (pathophysiological condition) and CFRg and FFRmyog (in the presence of the guide wire) were obtained in native and residual lesions. A strong linear correlation was found between CFR and CFRg [CFR = CFRg x 0.689 + 1.271 (R2= 0.99) for 0.46 mm and CFR = CFRg x 0.757 + 1.004 (R2= 0.99) for 0.35 mm] and between FFRmyo and FFRmyog [FFRmyo = FFRmyog x 0.737 + 0.263 (R2= 0.99) for 0.46 mm and FFRmyo = FFRmyog x 0.790 + 0.210 (R2= 0.99) for 0.35 mm]. This study establishes a strong correlation between CFR and CFRg and between FFRmyo and FFRmyog, which could be used to obtain the true state of occlusion in the coronary artery during angioplasty.