title: Diagnostic and Prognostic Implications of Coronary Flow Capacity: A Comprehensive Cross-Modality Physiological Concept in Ischemic Heart Disease.
abstract: OBJECTIVE
  The purpose of this study is to evaluate whether coronary flow capacity (CFC) improves discrimination of patients at risk for major adverse cardiac events (MACE) compared with coronary flow reserve (CFR) alone, and to study the diagnostic and prognostic implications of CFC in relation to contemporary diagnostic tests for ischemic heart disease (IHD), including fractional flow reserve (FFR).
  
  
  BACKGROUND
  Although IHD results from a combination of focal obstructive, diffuse, and microcirculatory involvement of the coronary circulation, its diagnosis remains focused on focal obstructive causes. CFC comprehensively documents flow impairment in IHD, regardless of its origin, by interpreting CFR in relation to maximal flow (hyperemic average peak flow velocity [hAPV]), and overcomes the limitations of using CFR alone. This is governed by the understanding that ischemia occurs in vascular beds with substantially reduced hAPV and CFR, whereas ischemia is unlikely when hAPV or CFR is high.
  
  
  METHODS
  Intracoronary pressure and flow were measured in 299 vessels (228 patients), where revascularization was deferred in 154. Vessels were stratified as having normal, mildly reduced, moderately reduced, or severely reduced CFC using CFR thresholds derived from published data and corresponding hAPV percentiles. The occurrence of MACE after deferral of revascularization was recorded during 11.9 years of follow-up (quartile 1: 10.0 years, quartile 3: 13.4 years).
  
  
  RESULTS
  Combining CFR and hAPV improved the prediction of MACE over CFR alone (p = 0.01). After stratification in CFC, MACE rates throughout follow-up were strongly associated with advancing impairment of CFC (p = 0.002). After multivariate adjustment, mildly and moderately reduced CFC were associated with a 2.1-fold (95% confidence interval: 1.1 to 4.0; p = 0.017), and 7.1-fold (95% confidence interval: 2.9 to 17.1; p < 0.001) increase in MACE hazard, respectively, compared with normal CFC. Severely reduced CFC was identified by FFR ≤0.80 in 90% of cases, although ≥40% of vessels with normal or mildly reduced CFC still had an FFR ≤0.80.
  
  
  CONCLUSIONS
  CFC provides a cross-modality platform for the diagnosis and risk-stratification of IHD and enriches the interpretation of contemporary diagnostic tests in IHD.
authors.affiliation: AMC Heartcenter, Academic Medical Center-University of Amsterdam, Amsterdam, the Netherlands; Cardiovascular Institute, Hospital Clínico San Carlos, and Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. Electronic address: t.p.vandehoef@amc.uva.nl.
authors.forename: Tim P
authors.initials: TP
authors.lastname: van de Hoef
authors.affiliation: Cardiovascular Institute, Hospital Clínico San Carlos, and Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; ThoraxCenter, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Mauro
authors.initials: M
authors.lastname: Echavarría-Pinto
authors.affiliation: AMC Heartcenter, Academic Medical Center-University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Martijn A
authors.initials: MA
authors.lastname: van Lavieren
authors.affiliation: Department of Cardiology, Amphia Hospital, Breda, the Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Meuwissen
authors.affiliation: ThoraxCenter, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Cardiology, Imperial College, London, United Kingdom.
authors.forename: Patrick W J C
authors.initials: PW
authors.lastname: Serruys
authors.affiliation: AMC Heartcenter, Academic Medical Center-University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Jan G P
authors.initials: JG
authors.lastname: Tijssen
authors.affiliation: Cardiovascular Institute, Hospital Clínico San Carlos, and Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.affiliation: Cardiovascular Institute, Hospital Clínico San Carlos, and Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Escaned
authors.affiliation: AMC Heartcenter, Academic Medical Center-University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
mesh_terms: D000368:Aged; D001783:Blood Flow Velocity; D006328:Cardiac Catheterization; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D003326:Coronary Circulation; D023921:Coronary Stenosis / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy; D055414:Myocardial Perfusion Imaging; D009204:Myocardial Revascularization; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
keywords: coronary flow reserve; coronary microcirculation; fractional flow reserve; microvascular ischemia; nonobstructive flow impairment