Coronary Heart Disease Disturbed Coronary Hemodynamics in Vessels With Intermediate Stenoses Evaluated With Fractional Flow Reserve A Combined Analysis of Epicardial and Microcirculatory Involvement in Ischemic Heart Disease Mauro Echavarria-Pinto, MD; Javier Escaned, MD, PhD; Enrico Macías, MD; Miguel Medina, MD; Nieves Gonzalo, MD, PhD; Ricardo Petraco, MD; Sayan Sen, MBBS; Pilar Jimenez-Quevedo, MD, PhD; Rosana Hernandez, MD, PhD; Rafael Mila, MD; Borja Ibañez, MD, PhD; Ivan J. Nuñez-Gil, MD; Cristina Fernández, MD, PhD; Fernando Alfonso, MD, PhD; Camino Bañuelos, MD; Eulogio García, MD; Justin Davies, MBBS, PhD; Antonio Fernández-Ortiz, MD, PhD; Carlos Macaya, MD, PhD Background—In chronic ischemic heart disease, focal stenosis, diffuse atherosclerotic narrowings, and microcirculatory dysfunction (MCD) contribute to limit myocardial flow. The prevalence of these ischemic heart disease levels in fractional flow reserve (FFR) interrogated vessels remains largely unknown. Methods and Results—Using intracoronary measurements, 91 coronaries (78 patients) with intermediate stenoses were classified in 4 FFR and coronary flow reserve (CFR) agreement groups, using FFR>0.80 and CFR0.80, most (63%) presented disturbed hemodynamics: abnormal CFR in 28 (52%) and MCD in 18 (33%). Vessels with FFR>0.80 presented higher IMR [adjusted mean 27.6 (95% confidence interval, 23.4–31.8)] than those with FFR≤0.80 [17.3 (95% confidence interval, 13.0–21.7), p=0.001]. Atherosclerotic burden was inversely correlated with CFR (r=−0.207, P=0.055), and in vessels with FFR>0.80 and CFR0.80 present disturbed hemodynamics. Integration of FFR, CFR, and IMR supports the existence of differentiated patterns of ischemic heart disease that combine focal and diffuse coronary narrowings with variable degrees of MCD. (Circulation. 2013;128:2557-2566.) Key Words: coronary disease ◼ microcirculation ◼ physiology
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hronic ischemic heart disease (IHD) is a multifactorial entity that occurs both in the presence or absence of obstructive coronary artery disease (CAD).1 Fractional flow reserve (FFR) has become a standard method to assess obstructive CAD in the catheterization laboratory2 following the demonstration that decision-making based on FFR results in better patients outcomes than angiography-guided revascularization.3 However, identification of other factors contributing to IHD, such as diffuse atherosclerotic narrowing (DAN) and microcirculatory dysfunction (MCD), remains largely elusive to the simplified model of physiological assessment provided by the
FFR. This diagnostic gap is important because it remains plausible that patients with normal FFR values and MCD might have a worse prognosis.4 The same applies to the presence of DAN, frequently overlooked during angiography, which may cause myocardial ischemia5 and influence long-term outcome.6
Editorial see p 2551 Clinical Perspective on p 2566 When combined with FFR, coronary flow reserve (CFR) and microcirculatory resistance could provide additional insights on the contribution of obstructive CAD, DAN and
Received January 16, 2013; accepted August 30, 2013. From the Cardiovascular Institute, Hospital Clinico San Carlos, Madrid, Spain (M.E.-P., J.E., E.M., M.M., N.G., P.J.-Q., R.H., R.M. B.I., I.J.N.-G., F.A., C.B., E.G., A.F.-O., C.M.); Centro Nacional de Investigaciónes Cardiovasculares Carlos III (CNIC), Madrid, Spain (M.E.-P., J.E., B.I., A.F.-O.); Imperial College Healthcare and NHS Trust, London, UK (R.P., S.S., J.D.); and Clinical Epidemiology Unit, Hospital Clinico San Carlos, Madrid, Spain (C.F.). The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIRCULATIONAHA. 112.001345/-/DC1. Correspondence to Javier Escaned, MD, PhD, Instituto Cardiovascular, Hospital Clinico San Carlos, Madrid, Spain, Centro Nacional de Investigaciónes Cardiovasculares Carlos III (CNIC), Madrid, Spain. E-mail
[email protected] © 2013 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.112.001345
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2558 Circulation December 17, 2013 MCD to IHD. In this study, we performed a comprehensive assessment of coronary hemodynamics in vessels with intermediate stenoses, using FFR, CFR and the index of microcirculatory resistance (IMR).7,8 In addition, the Gensini score was recalled as a surrogate of atherosclerotic burden.9 The obtained data were combined to outline 3 separate patterns of atherosclerotic involvement in IHD: focal epicardial stenoses, DAN, and MCD.8
Methods Study Population Patients with a clinical indication for FFR interrogation of ≥1 intermediate coronary stenoses (40% to 70% diameter stenosis by quantitative coronary angiography), investigated at Hospital Clinico San Carlos, Madrid, Spain, were prospectively studied. Culprit vessels of acute coronary syndromes, serial stenoses, and marked diffuse narrowings were excluded. Very distal narrowings, not amenable for revascularization (vessel diameter 0.80. When compared with arteries with FFR≤0.80, vessels with FFR>0.80 presented higher IMR [27.6 (95% confidence interval [CI], 23.4–31.8) versus 17.3 (95% CI, 13.0=−21.7); P=0.001] and CFR values [2.1 (95% CI, 1.8=−2.3) versus 1.8 (95% CI, 1.5=−2.0); P=0.035; adjmeans)]. Remarkably, when CFR and IMR were used as dichotomous variables, a high number of vessels with normal FFR presented abnormal CFR or IMR: 28 (51.9%) had Table 2. General Characteristics of Epicardial Stenoses Included in Study (n=91) Stenosis location Left anterior descending artery
39 (42.9)
Circumflex coronary artery
21 (23.1)
Right coronary artery
31 (34.1)
Quantitative coronary angiography Reference diameter, mm Minimum lumen diameter, mm Diameter stenosis, % Lesion length, mm
3.05±0.64 1.31±0.43 46.99±12.25 7.80±3.56
Coronary physiological parameters Pa, mm Hg*
79.4±20.7
Pd, mm Hg*
64.7±20.8
FFR
0.81±0.12
CFR IMR, U
1.94±0.80 18 (12.1–29.1)
Tmnbas, seg
0.73±0.48
Tmnhyp, seg*
0.37±0.21
Values are mean±SD, median (25th–75th), or n (%). CFR indicates coronary flow reserve; FFR, fractional flow reserve; IMR, index of microcirculatory resistance; Pa, aortic pressure; Pd, distal pressure; Tmnbas, basal mean transit time; and Tmnhyp, hyperemic mean transit time. *During stable hyperaemia.
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2560 Circulation December 17, 2013 low-CFR and 18 (33.3%) high-IMR. Consequently, only 20 (37%) vessels with FFR >0.80 had concordant normal values of all 3 indexes. Finally, within the normal FFR group, classification agreement between dichotomized values of CFR and IMR was low (kappa of −0.098; P=0.441). They were concordant only in 24 (44.44%), and in 30 (55.6%) arteries a classification disagreement was observed: CFR
