The curious incident of CFVR in clinical practice

This editorial refers to ‘Coronary flow velocity reserve predicts adverse prognosis in women with angina and no obstructive coronary artery disease: results from the iPOWER study’†, by J. Schroder et al., on page 228. The coronary flow velocity reserve (CFVR) between baseline and peak effect of a coronary vasodilator makes it possible to derive an index of coronary flow reserve (CFR) in the left anterior descending artery territory. The evaluation of CFR by combining transthoracic Doppler assessment of coronary flow velocities with vasodilator stress has entered the echo lab as an effective modality for both diagnostic and prognostic purposes; and CFVR works. It works in identifying strata of risk in several clinical scenarios. In the impeccably designed study in this issue of the European Heart Journal in women without large vessel coronary artery disease (CAD) and acute myocardial infarction, CFVR could be assessed in the vast majority of patients.1 An impaired CFVR, atherosclerosis, and hypertension were independent predictors of the composite outcome of cardiovascular death, myocardial infarction, heart failure, stroke, and coronary revascularization.1 Impaired CFVR was also associated with all-cause mortality and an increased risk of repeated hospital admission for angina pectoris. The authors conclude that the assessment of CFVR should be considered in angina patients to identify subgroups likely to benefit from intensified treatment. These results are not unexpected, since there is a large body of evidence showing that CFVR is related to hard events and mortality, when reduced independently of other cofactors.2,3 However, the strength of the study comes from a large sample appropriately selected and followed-up for a congruous number of years. The authors decided on a statistically derived CFVR cut-off value of 2.25, which is not that usually used in clinical practice, conventionally set at 2. The continuous value of CFVR has been demonstrated to work better in risk stratification: the lower the value, the higher the chance to experience events over time.4 The age- and gender-specific cut-offs have already been reported, and a value of CFVR ≤2.0 provides the optimal prognostication across all age groups and is gender independent.5 As said, CFVR has been demonstrated to provide key prognostic information in several subsets of patients and clinical scenarios in non-CAD (idiopathic dilated cardiomyopathy and hypertrophic cardiomyopathy)6,7 and CAD patients with micro- and macrovascular disease.4,8–10 This study is consistent with these previous observations demonstrating that the presence of microvessel dysfunction is an ominous prognosticator. The main question then is why is CFVR not so widely used in clinical practice in the face of its feasibility (>90% confirmed also in this study) and efficacy/effectiveness. There are cultural, technological, and practical barriers as to why CFVR is not included in the routine clinical armamentarium of the cardiologist. Microvascular CAD has been the field of study for a few experts who, on the basis of experimental, imaging, and clinical studies, have shown its importance in determining symptoms, events, and quality of life of patients.11 The burden of proof does not need to be reiterated here, but nonetheless CFVR seems to remain restricted to laboratories as an elegant research topic. The latest ESC version of the chronic coronary syndromes guidelines does list microvascular disease as a cause for angina pectoris, but the topic is left unaddressed properly without a thorough clinical and instrumental overview on how to deal with and manage these difficult patients.12 It is not the lack of evidence but the sign of the blurred vision of ischaemic heart disease where the central dogma of stenosis is never called into question. The next barrier is the method for the assessment of CFR. Physiologists and patho-physiologists have always overlooked non-invasive tools to assess CFR because of their many assumptions in measurement determination; however, these methods (nuclear or echo) have demonstrated their clinical value in assessing large samples of patients. Again, the search for the perfect tool should not limit the use of effective means that, albeit imperfect, are widely available and patient friendly. Moreover, as in any echo technique, the wide availability, the low cost, the portability, and the lack of ionizing radiation are unique features that make these tools highly suited for large-scale screening of samples. The next barrier to tear down is to encourage a more widespread us of stress echocardiography. CFVR has changed the way vasodilator stress testing is performed and for the first time a real quantitative measure has been associated with the highly qualitative and operator-dependent wall motion analysis. However, to perform CFVR, specific training is needed and high-end machines have to be used with dedicated software not available in all and for all. The technology barrier in echocardiography should be on the top of the list for machine developers because CFVR is too important to be left in the hands of a few willing researchers and clinicians. ‘Make it simple’ should be the new mantra in stress echocardiography, as its contribution to assess, risk-stratify, and follow-up patients is too precious and relevant. These authors did not use the recommended protocol with dual imaging assessment, wall motion, and CFVR.13 The choice is clearly due to the selection they made, including only patients with normal or near-normal coronary arteries at coronary angiography. Nonetheless, the double signal in flow and function moved CFVR from research to clinical laboratories, with the critical information of wall motion abnormalities strictly related to the presence of significant CAD. In other words, there is no need to perform coronary angiography to weigh up the value of CFVR; wall motion will tell the story (Figure 1). The last missing piece of the puzzle is how to restore CFR in the microcirculation, which is the best therapy to achieve it, and how the event rate changes when shifting one patient from one stratum of risk to another in relation to CFVR values.14 In any event, we have the tool, now we need to use it. The figure displays the potential patterns during dual imaging vasodilator stress testing and its relation to likelihood of events in the follow-up. No wall motion abnormalities and normal CFR at Doppler are related to a very low probability of experiencing events. At the opposite side of the spectrum of risk inducible wall motion abnormalities and reduced CFR at Doppler is related to the highest likelihood of experiencing events in the follow-up. Patients with no inducible wall motion abnormalities and reduce CFR at Doppler are at an intermediate risk of events.. The figure displays the potential patterns during dual imaging vasodilator stress testing and its relation to likelihood of events in the follow-up. No wall motion abnormalities and normal CFR at Doppler are related to a very low probability of experiencing events. At the opposite side of the spectrum of risk inducible wall motion abnormalities and reduced CFR at Doppler is related to the highest likelihood of experiencing events in the follow-up. Patients with no inducible wall motion abnormalities and reduce CFR at Doppler are at an intermediate risk of events.. Conflict of interest: none declared. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.