Instantaneous Wave-Free Ratio versus Fractional Flow Reserve guided intervention (iFR-SWEDEHEART): Rationale and design of a multicenter, prospective, registry-based randomized clinical trial Matthias Götberg, MD, PhD, a Evald H. Christiansen, MD, PhD, b Ingibjörg Gudmundsdottir, MD, PhD, c Lennart Sandhall, MD, d Elmir Omerovic, MD, PhD, e Stefan K. James, MD, PhD, f David Erlinge, MD, PhD, a and Ole Fröbert, MD, PhD g Lund, Helsingborg, Gothenburg, Uppsala, Örebro, Sweden; Skejby, Denmark; and Reykjavik, Iceland Background Instantaneous wave-free ratio (iFR) is a new hemodynamic resting index for assessment of coronary artery stenosis severity. iFR uses high frequency sampling to calculate a gradient across a coronary lesion during a period of diastole. The index has been tested against fractional flow reserve (FFR) and found to have an overall classification agreement of 80% to 85%. Whether the level of disagreement is clinically relevant is unknown. Clinical outcome data on iFR are scarce. This study is a registry-based randomized clinical trial, which is a novel strategy using health quality registries as on-line platforms for randomization, case record forms, and follow-up. Design/Methods iFR-SWEDEHEART is a multicenter, prospective, randomized, controlled, clinical open-label clinical trial. Two thousand patients with stable angina or acute coronary syndrome and an indication for physiology-guided assessment of one or more coronary stenoses will be randomized 1:1 to either iFR- or FFR-guided intervention. The randomization will be conducted online in the Swedish web-based system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART) registry. The trial has a non-inferiority design, with a primary combined end point of all-cause death, non-fatal myocardial infarction, and unplanned revascularization at 12 months. End points will be identified through national registries and undergo central blind adjudication to ensure data quality. Discussion The iFR-SWEDEHEART trial is an registry-based randomized clinical trial evaluating the safety and efficacy of the diagnostic method iFR compared to FFR. (Am Heart J 2015;170:945-50.) Randomized studies have demonstrated that physiological assessment of stenosis severity using fractional flow reserve (FFR) is superior to angiographic assessment in percuta- neous coronary intervention (PCI) and improves clinical outcome. 1–3 For routine assessment of intermediate coronary lesions, FFR carries a class I, level of evidence A, recommendation in current guidelines. 4,5 Despite the clinical benefit of FFR, the technique is underutilized and is currently employed in only 5-10% of cases. 6 Reasons for the low implementation rate of FFR may be the adenosine-related discomfort in patients and the extended duration of the procedure, particularly during assessment of multivessel disease. The instantaneous wave-free ratio (iFR) is a new physiological index for assessment of the hemodynamic severity of a coronary lesion. iFR is calculated by measuring the resting pressure gradient across a coronary lesion using high frequency sampling during the part of diastole when microvascular resistance is low and stable. 7 The main benefits of this method compared to FFR are that it does not require administration of Adenosine and that the results are immediate. Thus, iFR is not associated with patient discomfort, and the duration of the procedure can be reduced compared to FFR. The performance of iFR and FFR has been evaluated in several studies, with the diagnostic agreement of the two indices varying from 80% to 90% depending on whether the From the a Department of Cardiology, Lund University, Skåne University Hospital, Lund, Sweden, b Department of Cardiology, Aarhus University Hospital, Skejby, Denmark, c Department of Cardiology, Reykjavik University Hospital, Reykjavik, Iceland, d Department of Radiology, Helsingborg County Hospital, Helsingborg, Sweden, e Department of Cardiology, Sahlgrenska University, Gothenburg, Sweden, f Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden, and g Örebro University, Faculty of Health, Department of Cardiology, Örebro, Sweden. RCT# NCT02166736. Submitted April 12, 2015; accepted July 26, 2015. Reprint requests: Matthias Götberg, MD, PhD, Department of Cardiology, Lund University, Skåne University Hospital, Lund 22185, Sweden. E-mail: matthias.gotberg@med.lu.se 0002-8703 © 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ahj.2015.07.031