Wilbert Aarnoudse

Coronary thermodilution to assess flow reserve : validation in humans

Background—Guide wire–based simultaneous measurement of fractional flow reserve (FFR) and coronary flow reserve (CFR) is important to understand microvascular disease of the heart. The aim of this study was to investigate the feasibility of simultaneous measurement of FFR and CFR by one pressure-temperature sensor-tipped guide wire with the use of coronary thermodilution and to compare CFR by thermodilution (CFRthermo) with simultaneously measured Doppler CFR (CFRDoppl). Methods and Results—In 103 coronary arteries in 50 patients, a pressure-temperature sensor-tipped 0.014-inch floppy guide wire and a 0.014-inch Doppler guide wire were introduced. Both normal vessels and a wide range of stenotic vessels were included. With 3 mL of saline at room temperature used as an indicator, by hand-injection, thermodilution curves in the coronary artery were obtained in triplicate, both at baseline and at intravenous adenosine-induced maximum hyperemia. After adequate curve-fitting, CFRthermo was calculated from the ratio of inverse mean transit times and compared with CFRDoppl calculated by velocities at hyperemia and baseline. Adequate sets of thermodilution curves and corresponding CFRthermo could be obtained in 87% of the arteries versus 91% for Doppler CFR and 100% for FFR. CFRthermo correlated fairly well to CFRDoppl (CFRthermo=0.84 CFRDoppl+0.17;r =0.80;P <0.001), although individual differences of >20% between both indexes were seen in a quarter of all arteries. Conclusions—This study shows the feasibility of simultaneous measurement of FFR (by coronary pressure) and CFR (by coronary thermodilution) in humans by one single guide wire in a practical and straightforward way and will facilitate assessment of microvascular disease.

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 (Pw) 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 Pw, 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 Pwis 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.

Microvascular resistance is not influenced by epicardial coronary artery stenosis severity : experimental validation

Background—The effect of epicardial artery stenosis on myocardial microvascular resistance remains controversial. Recruitable collateral flow, which may affect resistance, was not incorporated into previous measurements. Methods and Results—In an open-chest pig model, distal coronary pressure was measured with a pressure wire, and the apparent minimal microvascular resistance was calculated during peak hyperemia as pressure divided by flow, measured either with a flow probe around the coronary artery (Rmicro app) or with a novel thermodilution technique (apparent index of microcirculatory resistance [IMRapp]). These apparent resistances were compared with the actual Rmicro and IMR after the coronary wedge pressure and collateral flow were incorporated into the calculation. Measurements were made at baseline (no stenosis) and after creation of moderate and severe epicardial artery stenoses. In 6 pigs, 189 measurements of Rmicro and IMR were made under the various epicardial artery conditions. Without consideration of collateral flow, Rmicro app (0.43±0.12 to 0.46±0.10 to 0.51±0.11 mm Hg/mL per minute) and IMRapp (14±4 to 17±7 to 20±10 U) increased progressively and significantly with increasing epicardial artery stenosis (P <0.001 for both). With the incorporation of collateral flow, neither Rmicro nor IMR increased as a result of increasing epicardial artery stenosis. Conclusions—After collateral flow is taken into account, the minimum achievable microvascular resistance is not affected by increasing epicardial artery stenosis.

Percutaneous coronary intervention or bypass surgery in multivessel disease? A tailored approach based on coronary pressure measurement

The optimal revascularization strategy, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG), for patients with multivessel coronary artery disease (MVD) remains controversial. The aim of the present study was to compare the long‐term outcomes after selective PCI of only hemodynamically significant lesions (fractional flow reserve, or FFR < 0.75) to CABG of all stenoses in patients with MVD. In 150 patients with MVD referred for CABG, FFR was determined in 381 coronary arteries considered for bypass grafting. If the FFR was less than 0.75 in three vessels or in two vessels including the proximal left anterior descending (LAD) artery, CABG was performed (CABG group). If only one or two vessels were physiologically significant (not including the proximal LAD), PCI of those lesions was performed (PCI group). Of the 150 patients, 87 fulfilled the criteria for CABG and 63 for PCI. There were no significant differences in the angiographic or other baseline characteristics between the two groups. At 2‐year follow‐up, no differences were seen in adverse events, including repeat revascularization (event‐free survival 74% in the CABG group and 72% in the PCI group). A similar number of patients were free from angina (84% in the CABG group and 82% in the PCI group). Importantly, the results in both groups were as good as the surgical groups in previous studies comparing PCI and CABG in MVD. In patients with multivessel disease, PCI in those with one or two hemodynamically significant lesions as identified by an FFR < 0.75 yields a similar favorable outcome as CABG in those with three or more culprit lesions despite a similar angiographic extent of disease. Catheter Cardiovasc Interv 2004;63:184–191.

Quantitative assessment of coronary microvascular function in patients with and without epicardial atherosclerosis

AIMS: The influence of atherosclerosis and its risk factors on coronary microvascular function remain unclear as current methods of assessing microvascular function do not specifically test the microcirculation in isolation. We examined the influence of epicardial vessel atherosclerosis on coronary microvascular function using the index of myocardial resistance (IMR). METHODS AND RESULTS: IMR (a measure of microvascular function) and fractional flow reserve (FFR, a measure of the epicardial compartment) were measured in 143 coronary arteries (116 patients). Fifteen patients (22 arteries, mean age 48+/-16 years) had no clinical evidence of atherosclerosis (control group). One hundred and one patients (121 arteries, mean age 63+/-11 years) had established atherosclerosis and multiple cardiovascular risk factors (atheroma group). Mean IMR in the control group (19+/-5, range 8-28) was significantly lower than in the atheroma group (25+/-13, range 6-75) (P

False-negative myocardial scintigraphy in balanced three-vessel disease, revealed by coronary pressure measurement

In nuclear perfusion imaging of the myocardium, a false-negative test result in patients with balanced three-vessel disease is a well-known pitfall. This paper describes a patient with typical chest pain and a negative myocardial perfusion scintigram. At coronary angiography, intermediate stenoses in the left anterior descending (LAD), left circumflex (LCX), and right coronary (RCA) arteries were present. Fractional flow reserve, measured by coronary pressure measurement, was 0.54, 0.56, and 0.66 respectively for the LAD, LCX, and RCA, unequivocally demonstrating the presence of balanced three-vessel disease. The patient underwent successful bypass surgery and remained event-free thereafter. (Int J Cardiovasc Intervent 2003; 5: 67-71)

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.

Acute myocardial infarction and underlying stenosis severity

The objective of this study was to investigate the underlying stenosis severity of the culprit lesion in acute myocardial infarction.

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 (Tmn) of the injectate can be calculated and is inversely proportional to coronary blood flow. Because microvascular resistance equals distal coronary pressure (Pd) divided by myocardial flow, the product Pd · Tmn 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/cm5. Inverse mean transit time correlated well to absolute blood flow (R2 = 0.93). Furthermore, an excellent correlation was found between IMR and TMR (R2 = 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. Catheter Cardiovasc Interv 2004; 62:56–63.

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.