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FFR/iFR: Are the Published Cutoffs Applicable in Athletes?

Quick Takes

  • Fractional flow reserve (FFR) and instantaneous wave-free ratio (Philips, Amsterdam, The Netherlands) represent proportional reductions in coronary blood flow across a stenosis compared with flow in the absence of obstruction. Importantly, neither assessment specifies an absolute reduction in blood flow across a lesion.
  • In athletes with higher coronary flow reserves than in the general population, similar FFR values could represent greater absolute reductions in flow.
  • A comprehensive, noninvasive assessment and recognition of additional or alternative causes of ischemia are critical when evaluating the athlete both in and out of the cardiac catheterization laboratory.

Invasive assessments of coronary physiology have revolutionized the approach to coronary revascularization in the cardiac catheterization laboratory. The use of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR [Philips, Amsterdam, The Netherlands]) has been associated with improved outcomes at a reduced cost, a rare combination in modern technology.1-3 Accordingly, the use of FFR or iFR now carries a Class 1 recommendation by the American College of Cardiology (ACC) and American Heart Association (AHA) for use in patients with angina and moderate-severity stenoses to guide the decision to proceed with percutaneous coronary intervention (PCI).4 However, whether this standard of care may be analogously applied to the competitive athlete is worth considering.

FFR is a physiologic index derived by comparing the pressures proximal and distal to a focal coronary stenosis during maximal vasodilation, achieved with the infusion of adenosine.5 Under low and constant resistance, the pressure gradient becomes a surrogate for flow, allowing the severity of stenosis to be better defined by quantitatively assessing the change in flow across a lesion. iFR is obtained under similar assumptions, although measurements are made without inducing hyperemia. Instead, the calculation is performed exclusively during a specific diastolic interval when resistances are low. In these contexts, the value achieved represents a percentage of what would be normal flow, rather than an absolute quantity. Across patients with similar FFR measurements, the absolute reduction in epicardial and subsequently myocardial blood flow may be significantly different depending on the coronary flow reserve. Although data are limited, current literature supports supranormal coronary flow reserves in endurance athletes.6 Consequently, with the same FFR as a nonathlete, an athlete may experience a greater absolute reduction in flow. Coupled with a higher myocardial oxygen demand during exercise, it is plausible to reason that athletes may experience ischemia at higher FFR measures. However, does this mean that a borderline or even slightly higher FFR value in an athlete may warrant revascularization?

The results of the landmark ISCHEMIA (International Study Of Comparative Health Effectiveness With Medical And Invasive Approaches) seemingly put a punctuation mark on the management of stable coronary disease regarding hard outcomes. Despite some limitations, no benefit was perceived favoring an invasive strategy over a conservative one, even in the context of FFR/iFR.7 The 2023 multisociety Guideline for the Management of Patients With Chronic Coronary Disease reflected this finding, supporting the use of maximally tolerated medical therapies prior to intervention.8 Beta-blockers, calcium channel blockers, and long-acting nitrates are considered first-line therapies for the management of angina in the setting of stable coronary disease. However, the adverse effects and performance limitations of these medications may be more appreciated and ultimately undesired in the athlete than in a nonathlete. Effectively, having a lower threshold for revascularization may help achieve symptom relief and maintain the current level of performance.

Moreover, it should be acknowledged that the ISCHEMIA trial did not specifically evaluate stable coronary disease in athletes. Is it possible that the implications of those with obstructive coronary disease who partake in intense endurance activities are different than their more sedentary counterparts? The RACER (Race Associated Cardiac Arrest Event Registry) study, which included almost 11 million marathon runners, evaluated the incidence and outcomes of cardiac arrest during marathons. Interestingly, it was found that cardiac arrests due to ischemia occurred largely in the absence of plaque rupture.9 This finding suggests that, in those with a fixed coronary obstruction, it is possible that the myocardial demand of vigorous endurance exercises may be of greater consequence than in those who participate in more recreational activities or simply not at all.

It is critical to note that myocardial ischemia is a complex process that may involve epicardial disease, microvascular dysfunction, endothelial dysfunction, inflammation, thrombosis, and even systemic factors. Indeed, the concept of ischemia and no obstructive coronary artery disease has been increasingly recognized. In the athlete with suspected ischemia, an exercise stress test eliciting symptoms before invasive testing may help with clinical decision-making in the catheterization laboratory, where there may already be a degree of uncertainty regarding the reliability of an invasive assessment. Because FFR and iFR exclusively address epicardial disease, consideration should be given for the aforementioned factors in the symptomatic athlete with significantly discordant FFR/iFR measurements and noninvasive testing. Although current diagnostics make it difficult to determine whether both epicardial and microvascular disease exist in the same patient, it stands to reason that atherosclerosis is not a disease isolated to the epicardial vessels. In those with documented ischemia on noninvasive tests without obstructive disease, additional testing including vasoreactivity testing, stress cardiac magnetic resonance imaging, or positron emission tomography with myocardial perfusion imaging may be helpful to make a definitive diagnosis.10

As the topics of ischemia and revascularization continue to evolve, more data are needed to determine the broad applicability of invasive tests such as FFR and iFR and whether they pertain to those who exercise vigorously. As with all patients, the management of stable coronary disease in the competitive athlete should incorporate lifestyle modification, risk factor management, medical therapies, and noninvasive testing. The decision to undergo invasive testing with the possibility of subsequent PCI should be a shared decision-making process that integrates severity of symptoms and lifestyle limitations, pharmacologic options, and the patient's goals of care. Recognizing that each of these may differ dramatically from the nonathlete, an approach that combines the clinical history with all carefully considered objective data ensures the best possible care of the athlete.


  1. De Bruyne B, Fearon WF, Pijls NH, et al. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med 2014;371:1208-17.
  2. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med 2012;367:991-1001.
  3. Fearon WF, Bornschein B, Tonino PA, et al.; Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) Study Investigators. Economic evaluation of fractional flow reserve-guided percutaneous coronary intervention in patients with multivessel disease. Circulation 2010;122:2545-50.
  4. Lawton JS, Tamis-Holland JE, Bangalore S, et al.; Writing Committee Members. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2022;79:e21-e129.
  5. Pijls NH, van Son JA, Kirkeeide RL, De Bruyne B, Gould KL. Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation 1993;87:1354-67.
  6. Hildick-Smith DJ, Johnson PJ, Wisbey CR, Winter EM, Shapiro LM. Coronary flow reserve is supranormal in endurance athletes: an adenosine transthoracic echocardiographic study. Heart 2000;84:383-9.
  7. Maron DJ, Hochman JS, Reynolds HR, et al.; ISCHEMIA Research Group. Initial invasive or conservative strategy for stable coronary disease. N Engl J Med 2020;382:1395-407.
  8. Virani SS, Newby LK, Arnold SV, et al.; Writing Committee Members. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2023;82:833-955.
  9. Kim JH, Malhotra R, Chiampas G, et al.; Race Associated Cardiac Arrest Event Registry (RACER) Study Group. Cardiac arrest during long-distance running races. N Engl J Med 2012;366:130-40.
  10. Gulati M, Levy PD, Mukherjee D, et al.; Writing Committee Members. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2021;78:e187-e285.

Clinical Topics: Sports and Exercise Cardiology, Invasive Cardiovascular Angiography and Intervention, Acute Coronary Syndromes

Keywords: Athletes, Fractional Flow Reserve, Myocardial, Atherosclerosis

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