Thermal anemometric assessment of coronary flow reserve with a pressure-sensing guide wire: an in vitro evaluation.

Assessment of coronary flow reserve (CFR) with a commercially available pressure-sensor-tipped guide wire using the principle of thermal anemometry could provide major clinical benefits both in determining and in distinguishing between epicardial and microvascular coronary artery disease. In constant-temperature thermal anemometry, the electrical power required to maintain an element at a constant temperature is a measure for the local shear rate. Here, the feasibility of applying this thermoconvection method to a pressure-sensing guide wire is investigated using an in vitro model. A theoretical relation between electrical power and steady shear rate based on boundary layer theory was tested in an experimental set-up. In steady flow, a reproducible relation between electrical power and shear rate was obtained with an overheat temperature of 20K, which was in good agreement with theory. The relation between shear rate and flow, however, depends on geometry of the artery and position of the guide wire inside the vessel. Although this means that this thermoconvection method is less useful for absolute flow measurements, CFR could be assessed even for unsteady flow using the steady calibration curve with a mean relative difference of (3±5)% compared to CFR derived from the golden standard using an ultrasonic flow measurement device.

Continuous infusion thermodilution for assessment of coronary flow: theoretical background and in vitro validation.

Direct volumetric assessment of coronary flow during cardiac catheterization has not been available so far. In the current study continuous infusion thermodilution, a method based on continuous infusion of saline into a selective coronary artery is evaluated. Theoretically, volumetric flow can be calculated from the known infusion rate (Q(i)), the temperatures of the blood (T(b)), the saline (T(i)), and the mixture downstream to the infusion site (T). We aimed to validate and optimize the measurement method in an in vitro model of the coronary circulation. Full mixing of infusate and blood was found to be the main prerequisite for accurate determination of the coronary flow. To achieve full mixing the influence of catheter design, infusion rate, and location of temperature measurement were assessed. We found that continuous infusion thermodilution slightly overestimated coronary flow determined by directly measured reference flow by 7+/-8%, over the entire physiological flow range of 50-250 ml/min. These results were found using a specially designed infusion catheter (infusion mainly through distally located sideholes), a high enough infusion rate (25 ml/min), and measurement of the mixing temperature between 5 and 8 cm distal from the tip of the infusion catheter. Absolute coronary flow rate can be measured reliably by the continuous infusion method when full mixing is present, under the conditions mentioned above.

Direct volumetric blood flow measurement in coronary arteries by thermodilution.

OBJECTIVES: This study sought to validate a new method for direct volumetric blood flow measurement in coronary arteries in animals and in conscious humans during cardiac catheterization. BACKGROUND: Direct volumetric measurement of blood flow in selective coronary arteries would be useful for studying the coronary circulation. METHODS: Based on the principle of thermodilution with continuous low-rate infusion of saline at room temperature, we designed an instrumental setup for direct flow measurement during cardiac catheterization. A 2.8-F infusion catheter and a standard 0.014-inch sensor-tipped pressure/temperature guidewire were used to calculate absolute flow (Q(thermo)) in a coronary artery from the infusion rate of saline, temperature of the saline at the tip of the infusion catheter, and distal blood temperature during infusion. The method was tested over a wide range of flow rates in 5 chronically instrumented dogs and in 35 patients referred for physiological assessment of a coronary stenosis or for percutaneous coronary intervention. RESULTS: Thermodilution-derived flow corresponded well with true flow (Q) in all dogs (Q(thermo) = 0.73 Q + 42 ml/min; R(2) = 0.72). Reproducibility was excellent (Q(thermo,)(1) = 0.96 x Q(thermo,)(2) + 3 ml/min; R(2) = 0.89). The measurements were independent of infusion rate and sensor position as predicted by theory. In the humans, a good agreement was found between increase of thermodilution-derived volumetric blood flow after percutaneous coronary intervention and increase of fractional flow reserve (R(2) = 0.84); reproducibility of the measurements was excellent (Q(thermo,)(1) = 1.0 Q(thermo,)(2) + 0.9 ml/min, R(2) = 0.97), and the measurements were independent of infusion rate and sensor position. CONCLUSIONS: Using a suitable infusion catheter and a 0.014-inch sensor-tipped guidewire for measurement of coronary pressure and temperature, volumetric blood flow can be directly measured in selective coronary arteries during cardiac catheterization.

Effect of phentolamine on the hyperemic response to adenosine in patients with microvascular disease.

For accurate measurement of the fractional flow reserve (FFR) of the myocardium, the presence of maximum hyperemia is of paramount importance. It has been suggested that the hyperemic effect of the conventionally used hyperemic stimulus, adenosine, could be submaximal in patients who have microvascular dysfunction and that adding alpha-blocking agents could augment the hyperemic response in these patients. We studied the effect of the nonselective alpha-blocking agent phentolamine, which was administered in addition to adenosine after achieving hyperemia, in patients who had microvascular disease and those who did not. Thirty patients who were referred for percutaneous coronary intervention were selected. Of these 30 patients, 15 had strong indications for microvascular disease and 15 did not. FFR was measured using intracoronary adenosine, intravenous adenosine, and intracoronary papaverine before and after intracoronary administration of the nonselective alpha blocker phentolamine. In patients who did not have microvascular disease, no differences in hyperemic response to adenosine were noted, whether or not alpha blockade was given before adenosine administration; FFR levels before and after phentolamine were 0.76 and 0.75, respectively, using intracoronary adenosine (p = 0.10) and 0.75 and 0.74, respectively, using intravenous adenosine (p = 0.20). In contrast, in patients who had microvascular disease, some increase in hyperemic response was observed after administration of phentolamine; FFR levels decreased from 0.74 to 0.70 using intracoronary adenosine (p = 0.003) and from 0.75 to 0.72 using intravenous adenosine (p = 0.04). Although statistically significant, the observed further decrease in microvascular resistance after addition of phentolamine was small and did not affect clinical decision making in any patient. In conclusion, when measuring FFR, routinely adding an alpha-blocking agent to adenosine does not affect clinical decision making.

Epicardial stenosis severity does not affect minimal microcirculatory resistance.

BACKGROUND: Whether minimal microvascular resistance of the myocardium is affected by the presence of an epicardial stenosis is controversial. Recently, an index of microcirculatory resistance (IMR) was developed that is based on combined measurements of distal coronary pressure and thermodilution-derived mean transit time. In normal coronary arteries, IMR correlates well with true microvascular resistance. However, to be applicable in the case of an epicardial stenosis, IMR should account for collateral flow. We investigated the feasibility of determining IMR in humans and tested the hypothesis that microvascular resistance is independent of epicardial stenosis. METHODS AND RESULTS: Thirty patients scheduled for percutaneous coronary intervention were studied. The stenosis was stented with a pressure guidewire, and coronary wedge pressure (P(w)) was measured during balloon occlusion. After successful stenting, a short compliant balloon with a diameter 1.0 mm smaller than the stent was placed in the stented segment and inflated with increasing pressures, creating a 10%, 50%, and 75% area stenosis. At each of the 3 degrees of stenosis, fractional flow reserve (FFR) and IMR were measured at steady-state maximum hyperemia induced by intravenous adenosine. A total of 90 measurements were performed in 30 patients. When uncorrected for P(w), an apparent increase in microvascular resistance was observed with increasing stenosis severity (IMR=24, 27, and 37 U for the 3 different degrees of stenosis; P<0.001). In contrast, when P(w) is appropriately accounted for, microvascular resistance did not change with stenosis severity (IMR=22, 23, and 23 U, respectively; P=0.28). CONCLUSIONS: Minimal microvascular resistance does not change with epicardial stenosis severity, and IMR is a specific index of microvascular resistance when collateral flow is properly taken into account.

A physiologically representative in vitro model of the coronary circulation.

With the development of clinical diagnostic techniques to investigate the coronary circulation in conscious humans, the in vitro validation of such newly developed techniques is of major importance. The aim of this study was to develop an in vitro model that is able to mimic the coronary circulation in such a way that coronary pressure and flow signals under baseline as well as hyperaemic conditions are approximated as realistically as possible and are in accordance with recently gained insights into such signals in conscious man. In the present in vitro model the heart, the systemic and coronary circulation are modelled on the basis of the elements of a lumped parameter mathematical model only consisting of elements that can be represented by segments in an experimental set-up. A collapsible tube, collapsed by the ventricular pressure, represents the variable resistance and volume behaviour of the endocardial part of the myocardium. The pressure and flow signals obtained are similar to physiological human coronary pressure and flow, both for baseline and hyperaemic conditions. The model allows for in vitro evaluation of clinical diagnostic techniques.

Myocardial resistance assessed by guidewire-based pressure-temperature measurement: in vitro validation.

By injecting a few cubic centimeters of saline into the coronary artery and using thermodilution principles, mean transit time (T(mn)) of the injectate can be calculated and is inversely proportional to coronary blood flow. Because microvascular resistance equals distal coronary pressure (P(d)) divided by myocardial flow, the product P(d). T(mn) provides an index of myocardial resistance (IMR). In this in vitro study in a physiologic model of the coronary circulation, we compared IMR to true myocardial resistance (TMR) at different degrees of myocardial resistance and at different degrees of epicardial stenosis. Absolute blood flow was varied from 42 to 203 ml/min and TMR varied from 0.39 to 1.63 dynes. sec/cm(5). Inverse mean transit time correlated well to absolute blood flow (R(2) = 0.93). Furthermore, an excellent correlation was found between IMR and TMR (R(2) = 0.94). IMR was independent on the severity of epicardial stenosis and thus specific for myocardial resistance. Thus, using one single guidewire, both fractional flow reserve and IMR can be measured simultaneously as indexes of epicardial and microvascular disease, respectively, enabling separate assessment of both coronary arterial and microvascular disease.