ABC | Volume 111, Nº4, Octuber 2018

Original Article Martins ACS Fractional flow reserve-guided strategy Arq Bras Cardiol. 2018; 111(4):542-550 Characteristics of included studies Of the 7 studies included, 1was a prospective study and 6 had an observational, retrospective in design (Table 1 and Table 2). Quantitative synthesis of outcomes Mortality: We included 3 studies, a total of 2,074 patients, in the pooled analysis. The forest plot (Figure 2) describes the weighted meta-analysis for relative risk (RR) of mortality in ACS patients in comparison with non-ACS patients when revascularization decisions were based on FFR. Pooled analysis showed negligible heterogeneity among the studies (I2 = 0%; p = 0.78) and the ACS and non-ACS patients did not differ significantly; their pooled RR was 1.44 (95% CI = 0.89–2.35). Exclusion of any single study did not significantly alter the overall combined result. Cardiovascular mortality: We included 5 studies, a total of 3,144 patients, in the pooled analysis. The forest plot (Figure 2) describes the weighted meta-analysis for mortality risk of basing revascularization decisions on FFR. Pooled analysis showed significant heterogeneity among the studies (I2 = 70%; p = 0.01) and the ACS and non‑ACS patients did not differ significantly; their pooled RR was 1.29 (95% CI = 0.39–4.25). Exclusion of any single study did not significantly alter the overall combined result. Myocardial Infarction: 7 studies were included, a total of 5,107 patients, in the pooled analysis. Deferring lesions based on FFR was associated with a significant additional risk of MI (RR = 1.83; 95% CI = 1.39–2.40) in ACS patients versus non‑ACS patients. Figure 2 describes the weighted meta-analysis of MI. The pooled analysis showed negligible heterogeneity among the studies (I2 = 0%; p = 0.96). Target-vessel revascularization: We included 5 studies, a total of 3,475 patients, in the pooled analysis. The forest plot (Figure 2) describes the weighted meta-analysis of TVR in patients when revascularization decisions were based on FFR. Pooled analysis showed negligible heterogeneity among the studies (I2 = 39%; p = 0.16). ACS and non-ACS patients did not differ significantly in RR of TVR; their pooled RR was 1.46 (95% CI = 0.93–2.29). Study Bias Visual inspection of the funnel plots for the outcomes did not reveal any asymmetry among the studies. Further, the Begg rank correlation test was not statistically significant. Discussion This report provides a systematic review and a meta‑analysis comparing the strategy in patients in whom lesion treatment was deferred based on FFR, and no revascularization was undertaken in ACS patients to that in non-ACS patients. FFR‑guided revascularization in ACS patients appears to be as safe as in non‑ACS patients. 2,17-18 Briasoulis et al., 15 in a meta-analysis, evaluated FFR-guided management in NSTEMI patients, where a modest reduction in incidence of MI was noted, with no significant differences in incidence of major adverse cardiac events (MACE), death or all-cause mortality, and target-vessel revascularization between the FFR guided approach in comparison with coronary angiography‑guided approach. 15 Four important pathophysiological considerations need to be considered when comparing the FFR results in ACS patients to those of non-ACS patients: 1. Microvascular dysfunction: The timing of FFR measurement in the ACS patient is an important issue. As described above, immediately after MI, the initial, temporary microvascular injury caused by the inflammatory environment may artificially elevate the initial FFR measurements. Antithrombotic therapy, administered for 3 to 4 days to stabilize the plaque, may reduce microvascular dysfunction, and FFR may then reflect the true hemodynamic situation. This approach of waiting > 5 days to measure FFR in ACS patients was suggested by the European Society of Cardiology guidelines. 19-21 However, most referral centers that study FFR in ACS perform early invasive evaluation of ACS patients, within 48 h of presentation, a practice that could lead to artificially higher FFR values. 19,22-27,34,37,38 2. Plaque instability: At least two-thirds of lesions arising from vessels with < 50% stenosis are responsible for unstable syndromes involving plaque instability, assuming that these vessels previously had normal flow. A non‑flow‑limiting culprit lesion may be "anatomically significant" but "physiologically nonsignificant", and because FFR is not intended to evaluate plaque characteristics, care must be taken in the use of FFR in vessels with unstable characteristics but normal flow. 28,29 3. Myocardial mass involved: The mass of viable myocardium being perfused by the artery in question is relevant pathophysiologically to the interpretation of FFR results in ACS patients. The FFR value is inversely proportional to the ejection fraction: hence, a lower ejection fraction, which implies a large area of infarction with less viable myocardium, could produce a higher FFR reading for the same degree of stenosis. 14,30 4. Presentation type of ACS: Because ACS describe a range of myocardial ischemic states with distinct clinical and pathophysiological characteristics, the use of FFR should be differentiated by type of ACS. DANAMI3-PRIMULTI and COMPARE ACUTE were the only studies that evaluated the risk of events following FFR-guided PCI in patients with STEMI and MVD. 31,32 Of these, only COMPARE ACUTE reported the rate of events at follow-up in patients whose PCI was deferred based on FFR; patients who did not undergo additional revascularization had a similar event rate to those who were revascularized based on positive (elevated) FFR. On the other hand, FAME, which included 328 patients with ACS out of a total of 1,005 patients with MVD, reported similar rates of mortality, MI, or revascularization in non‑ST-segment elevation acute coronary syndrome (NSTE-ACS) patients who had PCI deferred based on an FFR cutoff value >0.80 compared to non-ACS patients. 24 However, the FAME study did not define the exact time of FFR measurement nor the lesions assessed (culprit vs . non‑culprit). Furthermore, the event rate in patients with deferred PCI based on FFR was not reported. In addition, the FAMOUS-NSTEMI trial compared a FFR‑guided versus an angiography‑only approach in NSTEMI and 544