Invasive evaluation of coronary microvascular dysfunction

Abstract

Coronary microvascular dysfunction (CMD) is a prevalent cause of ischemic heart disease and is associated with poorer quality of life and worse patient outcomes. Both functional and structural abnormalities of the microcirculation can generate ischemia in the absence of epicardial stenosis or worsen concomitant obstructive coronary artery disease (CAD). The invasive assessment of CMD allows for the evaluation of the entirety of the coronary vascular tree, from the large epicardial vessels to the microcirculation, and enables the study of vasomotor function through vasoreactivity testing. The standard evaluation of CMD includes vasomotor assessment with acetylcholine, as well as flow- and resistance-derived indices calculated with either thermodilution or Doppler guidewires. Tailored treatment based upon the information gathered from the invasive evaluation of CMD has been demonstrated to reduce the burden of angina; therefore, a thorough understanding of these procedures is warranted with the aim of improving the quality of life of the patient. This review summarizes the most widespread approaches for the invasive evaluation of CMD, with a focus on patients with ischemia and non-obstructive CAD.

Keywords: CAD; microvascular dysfunction; myocardial blood flow; myocardial ischemia and infarction.

Figure 1

Acetylcholine testing. Figure demonstrating the invasive physiological assessment of CMD and vasomotor disorders in a 65-year-old female, with repeated episodes of angina at rest. Coronary angiography identified no obstructive CAD. In Panel A and Panel B, baseline coronary angiography shows the wire advanced into the distal LAD and a resting ECG without repolarization abnormalities. Following the infusion of intracoronary acetylcholine (up to 200 mcg, Panel C and Panel D), the patient described chest pain with similar characteristics to her previous episodes, supported by an ECG with pronounced ST-segment depression in the anterior leads. Coronary angiography showed an absence of epicardial coronary spasm. After the infusion of intravenous adenosine, CFR and IMR were calculated, with normal values (Panel E). A final diagnosis of microvascular spasm was established

Figure 2

CFR calculation using thermodilution. Mean transit times (T_mn) are calculated as the mean of 3 measures at rest (blue) and after the induction of hyperemia with intravenous adenosine (orange). CFR is defined as the ratio between resting T_mn and hyperemic T_mn

Figure 3

CFR calculation using Doppler. From intracoronary Doppler flow signal, mean coronary flow velocity (CFV) can be derived (blue line depicting the edge of Doppler curves) as the average of several beats. CFR is calculated as the ratio between mean hyperemic CFV and mean resting CFV

Figure 4

Continuous thermodilution for the calculation of absolute flow and resistance. Clinical case depicting the measurement of absolute coronary flow and resistance using continuous thermodilution. A dedicated monorail microcatheter (RayFlow, Hexacath, Paris, France) with lateral holes allows for the continuous infusion of saline (Panel A). This microcatheter is advanced over a pressure–temperature sensor guidewire (PressureWire X, Abbott Vascular, Santa Clara, CA, USA), positioned toward the distal LAD in a patient with diffuse epicardial atherosclerosis (Panel B). Then, a continuous infusion of saline is started at a rate of 20 ml⋅min. The distal tip of the wire will measure the mixing temperature (resulting from the combination of infused saline with blood). Subsequently, the sensor is withdrawn into the catheter to measure the infusion temperature. This data will allow for the calculation of absolute coronary flow (Q, L⋅min) and absolute coronary resistance (R, mmHg⋅L⋅min) (Panel C)

Figure 5

Flow–pressure loops for the calculation of IHDPVS and microvascular conductance. An example of the calculation of epicardial and microcirculatory vascular conductance based on instantaneous hyperemic diastolic pressure velocity slopes (IHDPVS), derived from the pressure–flow velocity relationship. Panel A shows intracoronary Doppler measurements of hyperemic coronary flow velocity, in addition to a distal and aortic coronary pressure. Panel B shows a plot with hyperemic coronary flow velocity (Y-axis) and pressure (X-axis). IHDVPS is the slope of the pressure–flow relationship measured in mid to end-diastole and is expressed as a beta coefficient of a regression line, measured in cm⋅s⋅mmHg. Using distal coronary pressure (Pd) for its calculation, IHDVPS_Pd provides an estimation of microvascular conductance, whereas when using aortic pressure (Pa), IHDVPS_Pa estimates the overall vascular conductance. Separate assessment of epicardial conductance can be performed based on IHDVPS_Pa and IHDVPS_Pd (see text for details). Finally, the intercept of the slope with the X-axis provides a theoretical measurement of zero-flow pressure (Pzf), which has been used as a surrogate of extravascular microcirculatory compression. C_epi epicardial conductance, C_micro microvascular conductance, C_overall overall vascular conductance (combination of epicardial and microvascular). Image taken with permission from N. Van Der Hoeven