Vasodilators
The most commonly used vasodilators are dipyridamole and adenosine. A comparison between modes of application, and advantages and disadvantages of both methods is presented in Table 1.
CFVR could also be assessed during dobutamine stress echocardiography. However, it is not widely used since dobutamine increases coronary flow via different mechanisms compared with dipyridamole and adenosine.11 Both exercise and dobutamine are submaximal stimuli for coronary flow reserve (CFR) and technically more demanding for imaging of CFVR compared with dipyridamole and adenosine.3
Non-invasive or Invasive CFVR
A comparison between non-invasive (with transthoracic echocardiography) CFVR and invasive (during cardiac catheterisation and coronary angiography) FFR/CFR assessment is presented in Table 2.
Lear
ning Curve
CFVR assessment is an advanced echo tool requiring time and devotion. A detailed anatomical and technical knowledge is required in order to begin training. A period of supervision by a physician with considerable skills and experience in CFVR measurement is highly recommended. As with other techniques implicating technical skills, there is a learning curve and feasibility of CFVR measurement increases gradually in time.
Cold Pressor Test
It should be noted that both adenosine and dipyridamole induce a hyperaemic stimulus that relaxes vascular smooth muscle cells in coronary arteries in a fashion only partially dependent on endothelial function. The cold pressor test (CPT) is a well-validated, sympathetic stimulus able to induce hyperaemic vasodilation that depends totally on the endothelial release of nitric oxide (NO).16,17
CPT is performed according to a standardised protocol,18 by placing the subject’s hand and distal part of the forearm in ice-water slurry for 3 minutes. CPT-derived 
CFVR is measured as the ratio between coronary diastolic peak flow velocities at rest and during maximal hyperaemia (see Figure 4).
Pitfalls
There are several possible ways to make mistakes during CFVR assessment. Errors occur more often at the beginning of the learning curve and diminish significantly as operators gain experience. Common pitfalls include loss of flow signal during investigation, mapping different coronary artery tracts during the same study, misinterpretation of coronary arteries (e.g. diagonal or intermediate branches for LAD, or recurrent distal part of LAD for PDA) or misinterpretation of wall noise or epicardial space due to mild pericardial effusion and investigating right ventricular flow.
It should be noted that CFVR as a stand-alone technique can not distinguish between microvascular and macrovascular disease – the reason for a decrease in coronary reserve could be either epicardial coronary artery stenosis, or microvascular dysfunction, or both.