Impact of stenosis resistance and coronary flow capacity on fractional flow reserve and instantaneous wave-free ratio discordance: a combined analysis of DEFINE-FLOW and IDEAL.

Background: The pressure-derived parameters fractional flow reserve (FFR) and the emerging instantaneous wave-free ratio (iFR) are the most widely applied invasive coronary physiology indices to guide revascularisation. However, approximately 15-20% of intermediate stenoses show discordant FFR and iFR, and therapeutical consensus is lacking.

Aims: We sought to associate hyperaemic stenosis resistance index, coronary flow reserve (CFR) and coronary flow capacity (CFC) to FFR/iFR discordance.

Impact of core laboratory assessment on treatment decisions and clinical outcomes using combined fractional flow reserve and coronary flow reserve measurements - DEFINE-FLOW core laboratory sub-study.

Objective: The role of combined FFR/CFR measurements in decision-making on coronary revascularization remains unclear. DEFINE-FLOW prospectively assessed the relationship of FFR/CFR agreement with 2-year major adverse cardiac event (MACE) and target vessel failure (TVF) rates, and uniquely included core-laboratory analysis of all pressure and flow tracings. We aimed to document the impact of core-laboratory analysis on lesion classification, and the relationship between core-laboratory fractional flow reserve (FFR) and coronary flow reserve (CFR) values with clinical outcomes and angina burden during follow-up.

Three-Dimensional Angiographic Characteristics versus Functional Stenosis Severity in Fractional and Coronary Flow Reserve Discordance: A DEFINE FLOW Sub Study.

Background: Coronary angiography alone is insufficient to identify lesions associated with myocardial ischemia that may benefit from revascularization. Coronary physiology parameters may improve clinical decision making in addition to coronary angiography, but the association between 2D and 3D qualitative coronary angiography (QCA) and invasive pressure and flow measurements is yet to be elucidated.

Methods: We associated invasive fractional flow reserve (FFR), coronary flow reserve (CFR) and coronary flow capacity (CFC) with 2D- and 3D-QCA in 430 intermediate lesions of 366 patients.

Prognostic value of microvascular resistance and its association to fractional flow reserve: a DEFINE-FLOW substudy.

Objective: This study aimed to evaluate the prognostic value of hyperemic microvascular resistance (HMR) and its relationship with hyperemic stenosis resistance (HSR) index and fractional flow reserve (FFR) in stable coronary artery disease.

Methods: This is a substudy of the DEFINE-FLOW cohort (NCT02328820), which evaluated the prognosis of lesions (n=456) after combined FFR and coronary flow reserve (CFR) assessment in a prospective, non-blinded, non-randomised, multicentre study in 12 centres in Europe and Japan. Participants (n=430) were evaluated by wire-based measurement of coronary pressure, flow and vascular resistance (ComboWire XT, Phillips Volcano, San Diego, California, USA).

Characterization of quantitative flow ratio and fractional flow reserve discordance using doppler flow and clinical follow-up.

The physiological mechanisms of quantitative flow ratio and fractional flow reserve disagreement are not fully understood. We aimed to characterize the coronary flow and resistance profile of intermediate stenosed epicardial coronary arteries with concordant and discordant FFR and QFR. Post-hoc analysis of the DEFINE-FLOW study.

Respiration-related variations in Pd/Pa ratio and fractional flow reserve in resting conditions and during intravenous adenosine administration.

Aims: We evaluated the occurrence and physiology of respiration-related beat-to-beat variations in resting Pd/Pa and FFR during intravenous adenosine administration, and its impact on clinical decision-making.

Methods And Results: Coronary pressure tracings in rest and at plateau hyperemia were analyzed in a total of 39 stenosis from 37 patients, and respiratory rate was calculated with ECG-derived respiration (EDR) in 26 stenoses from 26 patients. Beat-to-beat variations in FFR occurred in a cyclical fashion and were strongly correlated with respiratory rate (R  = 0.

Principles and pitfalls in coronary vasomotor function testing.

Background: Coronary vasomotor dysfunction can be diagnosed in a large proportion of patients with angina in the presence of non-obstructive coronary artery disease (ANOCA) using comprehensive protocols for coronary vasomotor function testing (CFT). Although consensus on diagnostic criteria for endotypes of coronary vasomotor dysfunction has been published, consensus on a standardised study testing protocol is lacking.

Aims: In this review we provide an overview of the variations in CFT used and discuss the practical principles and pitfalls of CFT.

Coronary Flow Capacity to Identify Stenosis Associated With Coronary Flow Improvement After Revascularization: A Combined Analysis From DEFINE FLOW and IDEAL.

Background Coronary flow capacity (CFC), which is a categorical assessment based on the combination of hyperemic coronary flow and coronary flow reserve (CFR), has been introduced as a comprehensive assessment of the coronary circulation to overcome the limitations of CFR alone. The aim of this study was to quantify coronary flow changes after percutaneous coronary intervention in relation to the classification of CFC and the current physiological cutoff values of fractional flow reserve, instantaneous wave-free ratio, and CFR. Methods and Results Using the combined data set from DEFINE FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect -Combined Pressure and Doppler FLOW Velocity Measurements) and IDEAL (Iberian-Dutch-English), a total of 133 vessels that underwent intracoronary Doppler flow measurement before and after percutaneous coronary intervention were analyzed.

Objective Identification of Intermediate Lesions Inducing Myocardial Ischemia Using Sequential Intracoronary Pressure and Flow Measurements.

Background Although ischemic heart disease has a complex and multilevel origin, the diagnostic approach is mainly focused on focal obstructive disease as assessed by pressure-derived indexes. The prognostic relevance of coronary flow over coronary pressure has been suggested and implies that identification of relevant perfusion abnormalities by invasive physiology techniques is critical for the correct identification of patients who benefit from coronary revascularization. The purpose of this study was to evaluate the diagnostic potential of a sequential approach using pressure-derived indexes instantaneous wave-free ratio (iFR), fractional flow reserve (FFR), and coronary flow reserve (CFR) measurements to determine the number of intermediate lesions associated with flow abnormalities after initial pressure measurements.

Time course of coronary flow capacity impairment in ST-segment elevation myocardial infarction.

Background: Microvascular dysfunction in the setting of ST-elevated myocardial infarction (STEMI) plays an important role in long-term poor clinical outcome. Coronary flow reserve (CFR) is a well-established physiological parameter to interrogate the coronary microcirculation. Together with hyperaemic average peak flow velocity, CFR constitutes the coronary flow capacity (CFC), a validated risk stratification tool in ischaemic heart disease with significant prognostic value.

Long-Term Effects of Transcatheter Aortic Valve Implantation on Coronary Hemodynamics in Patients With Concomitant Coronary Artery Disease and Severe Aortic Stenosis.

Background As younger patients are being considered for transcatheter aortic valve implantation (TAVI), the assessment and treatment of concomitant coronary artery disease is taking on increased importance. Methods and Results Thirteen contemporary lower-risk patients with TAVI with severe aortic stenosis (AS) and moderate-severe coronary lesions were included. Patients underwent assessment of coronary hemodynamics in the presence of severe AS (pre-TAVI), in the absence of severe AS (immediately post-TAVI), and at longer-term follow-up (6 months post-TAVI).

Distal Evaluation of Functional performance with Intravascular sensors to assess the Narrowing Effect-combined pressure and Doppler FLOW velocity measurements (DEFINE-FLOW) trial: Rationale and trial design.

Background: It remains uncertain if invasive coronary physiology beyond fractional flow reserve (FFR) can refine lesion selection for revascularization or provide additional prognostic value. Coronary flow reserve (CFR) equals the ratio of hyperemic to baseline flow velocity and has a wealth of invasive and noninvasive data supporting its validity. Because of fundamental physiologic relationships, binary classification of FFR and CFR disagrees in approximately 30%-40% of cases.

Impact of clinical and haemodynamic factors on coronary flow reserve and invasive coronary flow capacity in non-obstructed coronary arteries: a patient-level pooled analysis of the DEBATE and ILIAS studies.

Aims: Coronary flow reserve (CFR) is a physiological index for the assessment of myocardial flow impairment due to focal or microcirculatory coronary artery disease (CAD). Coronary flow capacity (CFC) is another flow-based concept in diagnosing ischaemic heart disease, based on hyperaemic average peak velocity (hAPV) and CFR. We evaluated clinical and haemodynamic factors which potentially influence CFR and CFC in non-obstructed coronary arteries.

Contribution of Age-Related Microvascular Dysfunction to Abnormal Coronary: Hemodynamics in Patients With Ischemic Heart Disease.

Objectives: This study sought to investigate the contribution of age-related microcirculatory dysfunction to abnormal coronary hemodynamics in patients with coronary atherosclerosis.

Background: Impairment in myocardial blood supply in patients with coronary atherosclerosis can be accentuated due to age-related changes in microcirculatory function.

Methods: Intracoronary pressure and flow were measured with the Doppler technique in 299 vessels (228 patients), and the thermodilution technique in 120 vessels (99 patients).

Individual Lesion-Level Meta-Analysis Comparing Various Doses of Intracoronary Bolus Injection of Adenosine With Intravenous Administration of Adenosine for Fractional Flow Reserve Assessment.

Background: Intravenous infusion of adenosine is considered standard practice for fractional flow reserve (FFR) assessment but is associated with adverse side-effects and is time-consuming. Intracoronary bolus injection of adenosine is better tolerated by patients, cheaper, and less time-consuming. However, current literature remains fragmented and modestly sized regarding the equivalence of intracoronary versus intravenous adenosine.

Quantification of Myocardial Mass Subtended by a Coronary Stenosis Using Intracoronary Physiology.

Background: In patients with stable coronary artery disease, the amount of myocardium subtended by coronary stenoses constitutes a major determinant of prognosis, as well as of the benefit of coronary revascularization. We devised a novel method to estimate partial myocardial mass (PMM; ie, the amount of myocardium subtended by a stenosis) during physiological stenosis interrogation. Subsequently, we validated the index against equivalent PMM values derived from applying the Voronoi algorithm on coronary computed tomography angiography.

Pressure-derived estimations of coronary flow reserve are inferior to flow-derived coronary flow reserve as diagnostic and risk stratification tools.

Background: Pressure-derived coronary flow reserve (CFR) and pressure-bounded CFR (CFR) enable simple estimation of CFR from routine pressure measurements, but have been inadequately validated. We sought to compare CFR and CFR against flow-derived CFR (CFR) in terms of diagnostic accuracy, as well as regarding their comparative prognostic relevance.

Methods: We evaluated 453 intermediate coronary lesions with intracoronary pressure and flow measurements.

Assessing the Haemodynamic Impact of Coronary Artery Stenoses: Intracoronary Flow Versus Pressure Measurements.

Fractional flow reserve (FFR)-guided percutaneous coronary intervention results in better long-term clinical outcomes compared with coronary angiography alone in intermediate stenoses in stable coronary artery disease (CAD). Coronary physiology measurements have emerged for clinical decision making in interventional cardiology, but the focus lies mainly on epicardial vessels rather than the impact of these stenoses on the myocardial microcirculation. The latter can be quantified by measuring the coronary flow reserve (CFR), a combined pressure and flow index with a strong ability to predict clinical outcomes in CAD.

Fractional Flow Reserve or Coronary Flow Reserve for the Assessment of Myocardial Perfusion : Implications of FFR as an Imperfect Reference Standard for Myocardial Ischemia.

Purpose Of Review: Accumulating evidence exists for the value of coronary physiology for clinical decision-making in ischemic heart disease (IHD). The most frequently used pressure-derived index to assess stenosis severity, the fractional flow reserve (FFR), has long been considered the gold standard for this purpose, despite the fact that the FFR assesses solely epicardial stenosis severity and aims to estimate coronary flow impairment in the coronary circulation. The coronary flow reserve (CFR) directly assesses coronary blood flow in the coronary circulation, including both the epicardial coronary artery and the coronary microvasculature, but is nowadays less established than FFR.