Side effects and major adverse cardiac events caused by fractional flow reserve measurement: a systematic review and meta-analysis of 12,215 patients

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.