Background Current guidelines recommend revascularization based on fractional flow reserve (FFR) in angiographically intermediate coronary stenoses. Side effects of FFR caused by adenosine administration are usually transient with little relevance. However, major adverse cardiac events (MACE), such as coronary artery occlusion, may infrequently occur as a consequence of intracoronary wire manipulation and little is known about their incidence. This systematic review aims to analyze the rate of side effects including MACE caused by FFR measurement as reported in large multicenter studies. Methods A PubMed database query for “fractional flow reserve” of the type “multicenter study” identified 348 records. Subsequently, one retracted record was excluded, another record was excluded as it contained no digital object identifier, 52 records were excluded since access could not be obtained, and one was a duplicate. Of the 293 records screened, only 15 contained relevant information on adverse effects or events due to FFR measurement and had included at least 100 patients. To systematically report the frequency of adverse events, the micro average for each event type was calculated across all studies where it was described. Results This systematic review includes data from 15 studies with a total of 12,215 patients. Measurement of FFR was successful in 99.1% (5,163 of 5,210). Hyperemia for FFR measurement was usually induced by adenosine, in most cases administered intravenously. Adverse effects are summarized in Figure 1. With 34.5% (778 of 2,257) of patients reporting chest pain or discomfort, this was the most common side effect of adenosine administration. Dyspnea was noted by 20.0% (250 of 1,250) of patients. Heart-rhythm disturbances occurred in 3.3% (185 of 5,646) of patients. More specifically, a transient atrioventricular block was reported in 2.6% (115 of 4,396) of patients, whereas ventricular arrhythmia was considerably less frequent with 0.2% (11 of 5,864). Hypotension was described by 0.9% (14 of 1,574) of patients, vomiting or nausea by 0.9% (11 of 1,250), and bronchospasm by 0.2% (11 of 4,836). MACE were infrequent, but not negligible: the pressure wire used for FFR measurement was reported to cause coronary artery dissection in 0.2% (8 of 4,158) of patients, coronary artery occlusion in 0.2% (4 of 2,381) of patients, and coronary artery perforation in 0.1% (2 of 3,228) of patients. Conclusions Chest pain, dyspnea, and transient arrhythmias are commonly experienced by patients in the context of adenosine but bear limited clinical relevance. The analysis of a large patient cohort revealed that MACE caused by vessel injury, while infrequent, occur at a rate of approximately 0.5% and should hence be considered relevant. Funding Acknowledgement Type of funding sources: None.

Background Provisional side-branch stenting strategy is one of the preferred strategies for treatment of bifurcation lesions. Whereas using fraction flow reserve (FFR) for the physiologic assessment of jailed side branches is well studied, the reliability of resting indices such as instantaneous wave free ratio (iFR) is unknown. Methods Consecutive patients with provisional stenting of a bifurcation and a jailed side branch were enrolled in this study. FFR and iFR were measured and, after assuring absence of baseline shift and drift, both measurements were repeated after 3 minutes. Hyperemia was induced by intra-coronary adenosine with a dose of 48μg for the right coronary artery and 96μg for the left coronary artery. Cut-off for the assumed functional significance of a stenosis was 0.80 for FFR and 0.89 for iFR. The decision to treat the side branch was left to the interventionalist's discretion. Results 37 jailed side branches in 36 patients (age 68.4±8.2; male 81% (n=29)) were consecutively enrolled in the study. The main vessel was the left main in 3% (n=1), the left anterior descending (LAD) in 65% (n=24), the diagonal branch (D1) in 3% (n=1), the left circumflex artery (LCX) in 24% (n=9) and the right coronary artery (RCA) in 5% (n=2). The Medina classification revealed true bifurcation stenosis defined as Medina 1–1-1 prior to treatment in 35% (n=13). FFR showed 35% (n=13) of the stenosis to be functionally significant with a high reproducibility of the results (r=0.986). FFR showed a low correlation with angiographic assessment (r=−0.477). iFR indicated hemodynamic relevance in 38% of lesions (n=14) with a high reproducibility (r=0.967) and also correlated poorly with angiographic assessment (r=−0.271). iFR was found to closely correlate with FFR in jailed side branches (r=0.720, Figure 1A). Bland-Altman analysis showed iFR and FFR agreed with a mean difference between FFR and iFR of −0.054±0.146. In 81% (n=30) FFR and iFR showed the same results regarding functional significance. In 8% (n=3) FFR was ≤0.80 and iFR >0.89, in 11% (n=4) FFR was >0.80 and iFR was ≤0.89 (Figure 1B). Side branch treatment was performed in 32% (n=12). All of these lesions showed functional significance in FFR or iFR. Stent implantation was performed in 8% (n=3), balloon angioplasty in 19% (n=7) and balloon angioplasty with a drug-eluting balloon in 5% (n=2). Conclusions The results of this study confirm the poor correlation of angiographic and functional assessment of coronary artery stenoses. Our data show close agreement of iFR and FFR in stent-jailed side branches. Therefore, iFR can be considered as a reliable technique for guidance of provisional side branch stenting. Figure 1 Funding Acknowledgement Type of funding source: None

Objectives and Background: This study aims to evaluate whether the high correlation and classification agreement of the instantaneous wave-free ratio (iFR) and the resting distal coronary to aortic pressure ratio (P d /P a ) with the fractional flow reserve (FFR) can be confirmed in stent-jailed side branches (J-SB).Methods: Consecutive patients (n = 49) undergoing provisional stenting were prospectively enrolled and a physiological assessment of the J-SB (n = 51) was performed. FFR, iFR, and P d /P a were measured and the hemodynamic relevance was determined using cutoff values of ≤0.80, ≤0.89, and ≤0.92, respectively.Results: Both iFR (r = 0.75) and P d /P a (r = 0.77) correlated closely with FFR.Classification agreement with FFR was 78% for iFR (81% sensitivity, 77% specificity) and 75% for P d /P a (63% sensitivity and 80% specificity). However, angiographic diameter stenosis and pressure indices correlated poorly. For a threshold of ≥70% stenosis, agreement concerning hemodynamic relevance was found in 59% for FFR, 69% for iFR, and 61% for P d /P a . Conclusion:As reported for other lesion types, FFR and the adenosine-independent pressure indices iFR and P d /P a show close correlation and a high classification agreement of approximately 75%-80% in J-SB. Therefore, iFR can be regarded as a recommendable alternative to FFR for the guidance of provisional stenting in bifurcation lesions.