IJCS | Volume 32, Nº4, July/August 2019

328 Table 1 - A summary of the pivotal trials of invasive hemodynamic assessment Clinical trial (n) Age % Male Inclusion / coronary anatomy FAME 1 (2009) 1005 64.2 +/- 10.2 years (Angiography group) 64.6 +/- 10.3 years (FFR group) 74.0% Patients with indications for PCI who had stenosis > 50% in at least 2 of 3 major coronary vessels *67.4% had stable angina FAME 2 (2018) 888 63.5 +/- 9.4 years (PCI group) 63.9 +/- 9.6 years (Medical therapy group) 78.2% Patients with stable angina in whom PCI was being considered with at least one functionally significant stenosis as determined by FFR ≤ 0.80 DEFINE-FLAIR (2017) 2492 65.5 +/- 10.8 years (iFR group) 65.2 +/- 10.6 years (FFR group) 75.9% Patients with stable angina or ACS who had an indication for physiologically guided assessment of a coronary lesion (40 to 70% stenosis on visual assessment) *80.2% had stable angina iFR-SWEDEHEART (2017) 2037 67.6 +/- 9.6 years (iFR group) 67.4 +/- 9.2 years (FFR group) 74.7% Patients with stable angina or ACS who had an indication for physiologically guided assessment of a coronary lesion (40 to 80% stenosis on visual assessment) *62.1% had stable angina FFR: fractional flow reserve; iRF: instantaneous-wave free ratio PCI: percutaneous coronary intervention; ACS: acute coronary syndrome. than conservative management among populations enrolled in these trials. In the case of the pivotal Fractional Flow Reserve Versus Angiography for Multi- Vessel Evaluation (FAME) 1 and FAME 2 trials, 4,5 the study cohorts were predominantly older (median age of about 65 years old) and male and, in the former, all patients had multi-vessel CAD with at least two lesions with > 50% luminal narrowing (Table 1). Both studies demonstrated an improvement in the incidence of major adverse cardiovascular events when using a FFR-guided strategy in stable CAD, FAME 2 being halted prematurely due to the robust early benefit. 4,5 The key iFR studies, the Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization (DEFINE-FLAIR) and Instantaneous Wave-free Ratio versus Fractional Flow Reserve in Patients with Stable Angina Pectoris or Acute Coronary Syndrome (iFR-SWEDEHEART) trials, were comprised of similar population demographics (Table 1). Both studies demonstrated a non-inferiority of iFR compared to the gold standard FFR with respect to major cardiovascular outcomes. 6,7 As is often the case in clinical sports cardiology, it is prudent to consider whether care patterns that have emerged from these clinical trials are universally appropriate for use among competitive athletes. An important assumption when applying FFR (and iFR) cut-points is that they reflect the ischemic threshold of the population studied, belowwhich coronary supply is insufficient tomeet myocardial demands. It is noteworthy that endurance athletes have a unique supply/demand relationship whereby they regularly endure sustained increases in heart rate, blood pressure, and cardiovascular workload during training and competition. In doing so, they far exceed the peak myocardial oxygen demands of the typical study patients that have been enrolled in the FFR/iFR cut-point derivation trials. When considering the highmyocardial oxygen consumption and associated neuro-hormonal activation that is present at times of peak performance, it is likely that endurance athletes with focal CADwill experience significant myocardial demand ischemia despite FFR (and iFR) values that lie above the traditional cut-points. Issa et al. Coronary physiologic in endurance athletes Int J Cardiovasc Sci. 2019;32(4):326-330 Viewpoint