Physiological basis and long-term clinical outcome of discordance between fractional flow reserve and coronary flow velocity reserve in coronary stenoses of intermediate severity.
BACKGROUND
Discordance between fractional flow reserve (FFR) and coronary flow velocity reserve (CFVR) may reflect important coronary pathophysiology but usually remains unnoticed in clinical practice. We evaluated the physiological basis and clinical outcome associated with FFR/CFVR discordance.


RESULTS
We studied 157 intermediate coronary stenoses in 157 patients, evaluated by FFR and CFVR between April 1997 and September 2006 in which revascularization was deferred. Long-term follow-up was performed to document the occurrence of major adverse cardiac events: cardiac death, myocardial infarction, or target vessel revascularization. Discordance between FFR and CFVR occurred in 31% and 37% of stenoses at the 0.75, and 0.80 FFR cut-off value, respectively, and was characterized by microvascular resistances during basal and hyperemic conditions. Follow-up duration amounted to 11.7 years (Q1-Q3, 9.9-13.3 years). Compared with concordant normal results of FFR and CFVR, a normal FFR with an abnormal CFVR was associated with significantly increased major adverse cardiac events rate throughout 10 years of follow-up, regardless of the FFR cut-off applied. In contrast, an abnormal FFR with a normal CFVR was associated with equivalent clinical outcome compared with concordant normal results: ≤ 3 years when FFR <0.75 was depicted abnormal and throughout 10 years of follow-up when FFR ≤ 0.80 was depicted abnormal.


CONCLUSIONS
Discordance of CFVR with FFR originates from the involvement of the coronary microvasculature. Importantly, the risk for major adverse cardiac events associated with FFR/CFVR discordance is mainly attributable to stenoses where CFVR is abnormal. This emphasizes the requirement of intracoronary flow assessment in addition to coronary pressure for optimal risk stratification in stable coronary artery disease.
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.). t.p.vandehoef@amc.uva.nl.
Tim P
TP
van de Hoef
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Martijn A
MA
van Lavieren
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Peter
P
Damman
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Ronak
R
Delewi
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Martijn A
MA
Piek
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Steven A J
SA
Chamuleau
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Michiel
M
Voskuil
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
José P S
JP
Henriques
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Karel T
KT
Koch
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Robbert J
RJ
de Winter
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Jos A E
JA
Spaan
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Maria
M
Siebes
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Jan G P
JG
Tijssen
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Martijn
M
Meuwissen
From the AMC Heartcenter Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., P.D., R.D., M.A.P., J.P.S.H., K.T.K., R.J.d.W., J.G.P.T., M.M., J.J.P.); Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands (T.P.v.d.H., J.A.E.S., M.S.); Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.A.J.C., M.V.); and Amphia Hospital, Breda, The Netherlands (M.M.).
Jan J
JJ
Piek
D000368:Aged; D001783:Blood Flow Velocity / Q000502:physiology*; D023921:Coronary Stenosis / Q000453:epidemiology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000503:physiopathology*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D053805:Fractional Flow Reserve, Myocardial / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
coronary flow velocity reserve; coronary microcirculation; fractional flow reserve; stable coronary artery disease