CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 4, September/October 2023 252 AFRICA coronary pressure guidewire during CAG, to the concurrently recorded aortic pressure and is equal to 1 in a normal coronary artery. Values < 0.8 are interpreted as indicating physiologically significant stenosis and the need for revascularisation.7 Various agents are used to achieve maximal hyperaemia and minimal, constant coronary resistance. One of the most commonly used agents is adenosine.8 However, adenosine has some drawbacks. Adenosine exerts its effects on the heart through two receptors. It decreases cyclic adenosine monophosphate (cAMP) by inhibiting adenylate cyclase through its A1 receptor on the atria, ventricles, sinus node and AV node, or it increases cAMP production by activating adenylate cyclase in coronary endothelial and vascular smooth muscle cells through its A2 receptor. The side effects of adenosine, such as transient AV block and sinus arrest, occur through stimulation of the A1 receptors, whereas effects such as coronary vasodilatation occur through the A2 receptors. Some patients may also experience dyspnoea due to activation of the chemoreceptors in the carotid sinus.9,10 Patients with afferent reflex activation may have a feeling of discomfort in the chest and chest pain that is relieved by theophylline.11-13 In some patients during FFR, adenosine has also been observed to cause ventricular arrhythmias.14 Furthermore, there is evidence that adenosine may be an inducer of epicardial vasoconstriction in patients with endothelial dysfunction.15 Consequently, adenosine has significant side effects, including angina, breathlessness, nausea and AV block, which limit its use.16 Given these limitations of adenosine, the initial measurement of Pd/Pa can provide an idea of the severity of the lesion without the need to use a hyperaemic agent. In a retrospective study of 520 lesions in 527 patients, three groups were formed according to baseline Pd/Pa and post-adenosine FFR measurements: a treatment group, a deferred treatment group and an indeterminate group. Patients with baseline Pd/Pa ≤ 0.86 were included in the treatment group, those with Pd/Pa of 0.87–0.99 were in the undetermined group, and those with Pd/Pa = 1 were in the deferred group. Adenosine was then administered to the indeterminate group, while those with FFR ≤ 0.80 were included in the treatment group, and those with FFR > 0.86 were in the deferral group. In that study, which used a strategy called hybrid baseline Pd/ Pa-FFR, no significant difference in major cardiac events was observed at the five-year follow up. Therefore, adenosine could have been avoided in 14% of the patients, the positive predictive value (PPV) for FFR-guided critical lesion detection was 100% and the negative predictive value (NPV) for exclusion was 100%. It was concluded that this hybrid method may reduce the need for hyperaemia.1 In a single-centre retrospective study of 483 patients with 528 lesions, Mamas et al. found a strong association between resting Pd/Pa and FFR values. In their cohort, 48% of patients did not require adenosine for FFR measurement using this protocol. It was also suggested that in the case of a Pd/Pa value > 0.96, there is no need for adenosine (NPV 93%). The authors noted that the Pd/Pa ratio had a relatively high PPV (95%) and NPV (93%) in predicting a positive FFR result and stated that this finding may reduce the need for adenosine infusion.17 Another study found that iFR, a method of studying coronary artery pressure flow without the use of a hyperaemic agent, and baseline Pd/Pa values correlated with each other.18,19 On the other hand, in the iFR SWEDEHEART trial, the iFR-guided revascularisation strategy was non-inferior to FFR in predicting 12-month major cardiac events.20 In our study, the baseline FFR value, that is, the resting Pd/Pa ratio, was lower in the Q1 group, where adenosine measurements were also lower, but after adenosine infusion, it was even lower in the Q1 and Q2 groups than in the Q3 and Q4 groups. In addition, the percentage change in FFR value was significantly lower in the Q3 and Q4 groups. Therefore, according to our study, one of the indicators that the lesion is unlikely to be critical is if the baseline Pd/Pa measurement is ≥ 0.92. The RESOLVE study was designed to evaluate the diagnostic accuracy of iFR and the Pd/Pa ratio for FFR.2 In that study of 1 768 patients, the primary objective was to identify specific iFR and Pd/Pa cut-off values (based on an FFR cut-off value of 0.80) and the proportion of patients above these cut-off values with 90% accuracy in predicting ischaemic and non-ischaemic FFR. For an FFR of 0.80, the best cut-off value for iFR was 0.90 (95% CI: 0.79–0.83; overall accuracy: 80.4%), and for Pd/ Pa it was 0.92 (95% CI: 0.80–0.84; overall accuracy: 81.5%), with no difference between resting measurements. iFR and Pd/Pa were 90% predictive of positive or negative FFR values in 64.9 and 48.3% of lesions, respectively. The overall precision of both non-hyperaemic indices was 80%. As a result of that study, when FFR was accepted as the reference method, iFR and Pd/Pa were found to be inadequate for guidance during the procedure, as there was a 20% discrepancy with FFR in the decisions made.2 In the VERIFY study, iFR was not independent of hyperaemia and correlated poorly with FFR. It was also found to be unreliable for clinical decision making in patients with coronary artery disease.21 In contrast to these studies, we found a significant correlation between adenosine FFR and baseline Pd/Pa measurements. During Pd/Pa measurement, the pressure in the microvascular bed is assumed to be constant at zero. Therefore, even in the presence of hyperaemia, the FFR value can be correlated with the Pd/Pa value. Another view is that as the lesion becomes critical, vasodilatation and autoregulatory capacity in the distal part of the lesion deteriorate, so that even if a hyperaemic agent is administered, an adequate response cannot be obtained. In other words, it has been observed that the decrease in resistance during hyperaemia varies according to the severity of the stenosis.22 Therefore, it can be said that the baseline Pd/Pa value is proportional to the FFR value with a hyperaemic agent. The results of our study support this view. As different patient groups have different pathophysiological processes, it is conceivable that baseline and FFR values may also be variable. For instance, it has been suggested that chronic hyperglycaemia in DM results in reduced vasodilatation and increased vascular resistance. In addition, DM has more extensive atherosclerosis with negative vessel remodelling and longer lesions.23 It is therefore reasonable to assume that these pathologies would affect FFR values. In a study based on the controversial value of FFR in diabetic patients due to microvascular dysfunction, no significant difference was found between the FFR values of diabetic and non-diabetic patients with similar stenotic lesions. Furthermore, the difference in FFR before versus after adenosine infusion was similar in diabetic and non-diabetic patients.24
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