Myocardial perfusion imaging by single-photon emission tomography (MPI SPECT) was shown to have high overall sensitivity and specificity estimated at 81.8% and 92.9%, respectively, as well as high positive predictive value (PPV) and negative predictive value (NPV) estimated as 90% and 86.7% respectively. Actually, this concordance between MPI SPECT and FFR results can be already expected and understood from the early validation studies on FFR itself that used MPI SPECT to assess the validity of FFR. In one study; I. Erhard, J. Rieber et al. [14] SPECT MPI and dobutamine stress Echocardiography were used as reference tests to evaluate FFR and by performing ROC analysis, the best cut-off value (highest sum of sensitivity and specificity) was found at 0.75. At this cut-off value using both non-invasive tests as a reference method, sensitivity and specificity were 83% and 77%. Another study, Caymaz O, Fak A et al. [15] prospectively evaluated 40 lesions using a 0.014 in. pressure wire during elective coronary angiography and compared the findings with those of myocardial perfusion 201 Thallium; the study concluded that FFRmyo seems to accurately predict the presence of ischemia on SPECT 201Tl in patients with Stable CAD, while QCA does not reliably assess the physiologic impact of the same lesions. Also, our results are consistent with some small previous studies that used the FFR as the gold standard test. In one study, Morteza Safi et al. [16] published at the Egyptian Heart Journal in 2016, conducted on 45 patients and concluded that there was a significant concordance between FFR and myocardial perfusion imaging for assessment of ischemia, for LAD territory involvement, myocardial perfusion imaging had a sensitivity, specificity, PPV, NPV, and accuracy of nearly 67%, 71%, 31%, 92%, and 70%; for LCX territory involvement, myocardial perfusion imaging had a sensitivity, specificity, PPV, NPV, and accuracy of nearly 100%, 60%, 33%, 100%, and 67% and for RCA territory involvement, myocardial perfusion imaging SPECT had a sensitivity, specificity, PPV, NPV, and accuracy of 100%, 60%, 20%, 100%, and 70%, respectively. In the study by Ilgin Sahiner et al. [17], the Quantitative MPI SPECT analysis compared to FFR has overall sensitivity and specificity of 85% and 84%, respectively, and it was superior to visual analysis.
Tao Zhoua et al. [18] reviewed 13 manuscripts. The pooled data at the vessel level was a sensitivity of 66% (95% CI, 57–74%) and specificity of 81% (95% CI, 70–89%).
In another meta-analysis, Ibrahim Danad et al. [19] evaluated MPI SPECT among other non-invasive tests to determine the diagnostic performance of these tests when compared to the gold standard FFR. At the patient level, 110 patients were involved, the summary sensitivity and specificity were 70% (59–80%) and 78% (68–87%) for MPI SPECT; and the positive and negative likelihood ratios were 3.4 (1.04–11.08) and 0.4 (0.19–0.83). At the vessel-level, 470 vessels were involved, pooled sensitivity was 57% (49–64%) and specificity was 75% (69–80%); the positive and negative likelihood ratios were 2.34 (1.61–3.42) and 0.55 (0.44–0.69). Neng Dai et al. [20] evaluated MPI SPECT among other non-invasive tests to determine the diagnostic performance of these tests when compared to the FFR. The overall sensitivity and specificity were 78% (71–84%) and 79% (70–87%) while the positive and negative likelihood ratios were 3.76 (2.52–5.63) and 0.28 (0.21–0.37). Juhani Knuuti et al. [21] published MPI SPECT overall sensitivity and specificity were 73% (62–82%) and 83% (71–90%) while the positive and negative likelihood ratios were 4.21 (2.62–6.76) and 0.33 (0.24–0.46).
On the other hand, some studies showed poor concordance between MPI SPECT and FFR especially in the patients with multi-vessel disease which was a more challenging situation to MPI SPECT evaluation due to the fact that MPI SPECT actually assesses the relative blood flow differences among vascular territories and so the possibility of balanced ischemia in the presence of more than one vessel disease may be an obstacle for accurate assessment. For example, in Narbeh Melikian et al. study [22] more than 60 patients (nearly 200 vascular territories) with angiographic more than one vessel coronary disease were prospectively scheduled to undergo rest/stress myocardial perfusion imaging and FFR in each vessel; in nearly 42% of patients, MPI and FFR detected identical ischemic territories, in 36%, MPI underestimated and in 22% overestimated the number of ischemic territories in comparison with FFR. There was no an accurate concordance between the ability of the two techniques to detect significant ischemia. On a per-patient basis, there was no accurate concordance between the ability of the two techniques to detect significant ischemia. In comparison with the FFR, the sensitivity, specificity, PPV, and NPV of MPI being able to detect myocardial ischemia was 76%, 38%, 66%, and 50%, respectively. Also on a per-vessel basis, there was no accurate concordance between the MPI and the FFR to detect significant ischemia. Tao Zhou et al. [18] stated that multi-vessel disease leads to the limitation of the myocardial perfusion imaging to assess the functional significance of coronary artery disease in patients with multi-vessel and left main coronary artery disease. In our small study, we excluded multivessel disease to avoid this dilemma especially with the limited resources that served the study on a relatively small sample of patients and we hope that the patients with multi-vessel and left main disease will be targeted in larger studies.
The instantaneous wave-free ratio (IFR) was shown to have sensitivity and specificity estimated as 90.9% and 100%, respectively, as well as positive predictive value (PPV) and negative predictive value (NPV) estimated as 100% and 93.3% respectively. Actually, this concordance between IFR and FFR results can be already expected and understood from the validation studies on IFR which compared both IFR and FFR against different other third-party tests and showed a great concordance between the two methods. In one study: the CLARIFY [23]. In nearly 50 vessels, the IFR, FFR, and HSR (hyperemic stenosis resistance) were compared. The IFR and FFR had an equally good diagnostic agreement with HSR.
In another study; Hwang D, Jeon K-H, et al. [24] included more than 100 consecutive patients with LAD stenosis who underwent both PET scan and invasive physiological assessment then optimal cut-off values of FFR, IFR, and resting Pd/Pa were assessed using PET-derived coronary flow reserve (CFR) and relative flow reserve (RFR) as references. The overall diagnostic accuracy of FFR, IFR, and resting Pd/Pa was not different for CFR < 2.0 (nearly FFR 70%, iFR 74%, and resting Pd/Pa 70%) and RFR < 0.75 (nearly FFR 74%, IFR 71%, and resting Pd/Pa 75%). Also, this concordance continued in large patient outcome trials conducted on both tests especially DEFINE-FLAIR [25] and IFR SWEDEHEART [26].
There are also some small studies were similar to our study design and compared IFR results directly to FFR results as a gold standard reference test.
In one study, Tobias Härle et al. [27] assessed the accuracy of the IFR prospectively in more than 100 patients with borderline coronary lesions; the IFR correlated strongly with the FFR (rs = 0.81; P < 0.0001). ROC analysis showed an area under the curve (AUC) equals 0.9106, suggesting the high reliability of the IFR as an accurate diagnostic test. The IFR-only technique with a treatment cut-point ≤ 0.89 revealed a diagnostic agreement with the FFR-only technique strategy in more than 120 lesions (nearly 83%) with a sensitivity of nearly 80%, a specificity of 86%. In another study, Alfredo Fede et al. [28] included more than 50 patients with borderline lesions and there was close agreement between the FFR and the IFR (R = 0.83, P < 0.0001). Deep Chandh Raja et al. [29] found that IFR correlated with FFR in all the subgroups and across all the vessels, without any influence for the heart rate or blood pressure on the correlation with FFR.
Also, there are some meta-analysis studies that addressed this point and clarified this concordance.
In one meta-analysis, Salvatore De Rosa et al. [30] evaluated nearly 6000 lesions. There was a significant correlation between the FFR and IFR of 0.798 (0.78–0.82; P < 0.001). Also, they compared IFR and FFR to a third independent reference standard that was invasive coronary flow reserve, non-invasive coronary flow reserve, hyperemic stenosis resistance, a combined reference standard of myocardial perfusion scintigraphy, and hyperemic stenosis resistance index or positron emission tomography perfusion imaging. There were no significant differences between IFR and FFR, both in terms of diagnostic accuracy, measured as the area under the ROC curve and in terms of the diagnostic agreement to the third comparator used in these studies.
In another meta-analysis Rohit Maini et al. [31] nearly 6000 lesions were evaluated. Pooled diagnostic accuracy estimates of IFR versus FFR were: sensitivity 0.78 (95% CI, 0.76–0.79), specificity 0.83 (0.81–0.84), the positive likelihood ratio was 4.54, negative likelihood ratio 0.28 (0.24–0.32), diagnostic odds ratio 17.38 (14.16–21.34), area under the ROC curve was 0.87, and the overall diagnostic accuracy was 0.81.
Limitations of the study
Despite the encouraging results presented in our small study, there were significant limitations including the small sample size and the exclusion of some types of patients that may be candidates for evaluation as patients with previous myocardial infarction and patients with multi-vessel disease.