- Email: [email protected]
Invasive Coronary Microcirculation Assessment During Myocardial Infarction
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
VOL. 64, NO. 18, 2014
ª 2014 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER INC.
http://dx.doi.org/10.1016/j.jacc.2014.08.028
EDITORIAL COMMENT
Invasive Coronary Microcirculation Assessment During Myocardial Infarction One Step Forward or Two Steps Back?* Gilles Rioufol, MD, PHD, Gérard Finet, MD, PHD
I
n acute coronary occlusion, ST-segment eleva-
(CFR) (5) and the index of microvascular resistance
tion myocardial infarction (STEMI) has been
(IMR) (6–10), making these promising candidates for
experimentally and clinically correlated with
assessing reperfusion lesions.
ischemic myocardial mass (area at risk), coronary
IMR has been of particular interest, as it shows less
reperfusion delay, and collateral circulation (1). Rapid
variation
coronary reperfusion, usually by primary percuta-
correlates with infarct size (6,7,10) and also with
neous coronary intervention (PPCI), provides the
improvement in left ventricular function (6–8,11,12).
principal means of limiting infarct size and improving
Recently, Fearon et al. (13) and Fukunaga et al. (10)
prognosis. It may, however, induce reperfusion
showed that IMR is a prognostic factor for heart
lesions, accounting for up to 40% to 50% of final
failure and death. When resistance is high, IMR
infarct size (2), making this a major research issue
increases and CFR decreases. IMR is typically <25 but
in therapeutic development (3). Much has been
may be double that in STEMI, with a cutoff between
learned thanks to cardiac magnetic resonance (CMR)
32 and 40 (6,9,10,12,13).
than
CFR
(11,12).
During
PPCI,
IMR
imaging, which notably enables noninvasive assess-
Whereas iterative measurements can be taken for
ment of the area at risk and reperfusion lesions
CMR (6,7), knowledge of microcirculation post-STEMI
(microvascular obstruction [MVO]) that develop in
using invasive IMR is usually limited to a single
the days after STEMI, and, later, specifics regarding
measurement taken at PPCI. Evolution and agree-
infarct size (4).
ment with CMR results, however, are essential to
In treating reperfusion lesions, however, the first minutes after coronary reperfusion are critical (1), thus making CMR ill-suited for detecting these lesions in acute MVO; consequently, other tools adapted for use in PPCI are now the focus of research and development.
improving understanding of the physiopathology of reperfusion lesions. SEE PAGE 1894
SERIAL PHYSIOLOGICAL MEASUREMENT AND CMR. From
this point of view, the study by Cuculi et al. (14) in
ENDOCORONARY PHYSIOLOGY TOOLS. Endocoro-
this issue of the Journal is exemplary. The authors
nary physiological measurements based on pressure
report follow-up of 82 acute STEMI patients in
wires could meet this aim. Presence and severity of
whom the culprit artery was studied on CFR, IMR,
MVO on CMR correlate with coronary flow reserve
and fractional flow reserve (FFR) both during PPCI and on post-intervention day 1 and month 6, with CMR measuring edema, MVO, and infarct size almost simultaneously during the 2 follow-up assessments.
*Editorials published in the Journal of the American College of Cardiology
The authors successfully met the challenge of
reflect the views of the authors and do not necessarily represent the
obtaining all of these measurements for almost half
views of JACC or the American College of Cardiology. From the Interventional Cardiology Department, Hospices Civils de Lyon, Claude Bernard University Lyon 1 and CARMEN INSERM 1060, Bron,
of the baseline population, with excellent reperfusion criteria making their findings easily generalizable.
France. Both authors have reported that they have no relationships
The 6-month lack of restenosis on angiography
relevant to the contents of this paper to disclose.
almost certainly rules out any focal epicardial
1906
Rioufol and Finet
JACC VOL. 64, NO. 18, 2014 NOVEMBER 4, 2014:1905–7
Coronary Microcirculation in MI
resistance effect, reinforcing the idea that analysis should focus on microcirculation. Ischemia duration
IMR
and area at risk on CMR, collaterality assessed on
100
MVO+ MVO-
**
*
90
FFR, MVO, and final infarct size were all measured,
NS (P=0.07)
80
providing data of virtually experimental quality.
70
We can draw a number of lessons from this study.
60
The first is that FFR evolves: in MVO without
**
**
50
epicardial stenosis, FFR diminishes significantly
40
over time. This reflects the epicardial resistance
30
induced by diffuse coronary atheroma seen in the
20
progressive normalization of residual hyperemia
10
capacity.
0
Evolution of IMR and CFR after PPCI is another interesting point, showing that microcirculation and its vasodilatory capacity begin to rally as of day 1,
ch
eo
G Mc
e
l. ta
)
f6
(re
o Yo
l. ta
)
f8
(re
e
l. ta
ne
Ah
with improvement continuing to 6 months, recov-
)
f9
(re
ga
na
ku Fu
l. ta
0)
f1
(re
e
ering normal values (IMR 24 22 and CFR 3.1 1.1).
F I G U R E 1 IMR Measurements in Literature According to
This evolution was already partially known for CFR
the Presence or Absence of MVO on Cardiac Magnetic
(15,16) but, although expected, had not been previ-
Resonance Imaging
ously demonstrated for IMR. This new work by Cuculi et al. (14), unlike earlier studies (6,8–10), found no difference in IMR according to presence/
4)
f1
(re
li e
cu
Cu
l. ta
Values are mean SD (except McGeoch et al. [6], which is median). IMR ¼ index of microvascular resistance; MVO ¼ microvascular obstruction. *p < 0.05. **p < 0.01.
absence of MVO (p ¼ 0.07) (Figure 1). However, while the presence of MVO in 47% of patients was associated with higher IMR and lower CFR, both nevertheless improved detection, reaching values
unsatisfactory way of identifying patients at high risk
comparable to those of patients free of MVO by
of MVO. Even so, invasive assessment remains an
6 months. Such variation and scatter in IMR values
important focus of research, as the moment of PPCI is
probably makes it unreliable as a substitute for
a unique opportunity for detecting reperfusion
CMR
lesions and setting up the therapeutic measures
in
assessing
reperfusion
lesion
severity,
although its prognostic value seems increasingly
needed to treat them.
confirmed (10,13). Thus, Cuculi et al. (14) are reporting important pathophysiologic
findings
that
bolster
our
un-
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
Gilles
Rioufol,
Cardiovascular
Hospital–Hospices
derstanding of microcirculation after myocardial
Civils de Lyon and INSERM 1060, Interventional
infarction. A single invasive measure of microcircu-
Cardiology, 28 Avenue Lépine, Bron, France 69677.
lation by IMR, CFR, or FFR thus now seems an
E-mail: [email protected].
REFERENCES 1. Ovize M, Thibault H, Przyklenk K. Myocardial conditioning: opportunities for clinical translation.
5. Hirsch A, Nijveldt R, Haeck JD, et al. Relation between the assessment of microvascular injury
8. Yoo SH, Yoo TK, Lim HS, Kim MY, Koh JH. Index of microcirculatory resistance as predictor for
Circ Res 2013;113:439–50.
by cardiovascular magnetic resonance and coronary Doppler flow velocity measurements in patients with acute anterior wall myocardial infarction. J Am Coll Cardiol 2008;51:2230–8.
microvascular functional recovery in patients with anterior myocardial infarction. J Korean Med Sci 2012;27:1044–50.
2. Fröhlich GM, Meier P, White SK, Yellon DM, Hausenloy DJ. Myocardial reperfusion injury: looking beyond primary PCI. Eur Heart J 2013; 34:1714–22. 3. Bekkers SC, Yazdani SK, Virmani R, Waltenberger J. Microvascular obstruction: underlying pathophysiology and clinical diagnosis. J Am Coll Cardiol 2010;55:1649–60.
6. McGeoch R, Watkins S, Berry C, et al. The index of microcirculatory resistance measured acutely predicts the extent and severity of myocardial infarction in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol Intv 2010;
9. Ahn SG, Lee SH, Lee JH, et al. Efficacy of combination treatment with intracoronary abciximab and aspiration thrombectomy on myocardial perfusion in patients with ST-segment elevation myocardial infarction undergoing primary coronary stenting. Yonsei Med J 2014;55:
4. Hundley WG, Bluemke DA, Finn JP, et al. ACCF/ ACR/AHA/NASCI/SCMR 2010 expert consensus
3:715–22.
606–16.
7. Payne AR, Berry C, Doolin O, et al. Microvas-
10. Fukunaga M, Fujii K, Kawasaki D, et al.
document on cardiovascular magnetic resonance: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J Am Coll Cardiol 2010;55:2614–62.
cular Resistance Predicts Myocardial Salvage and Infarct Characteristics in ST-segment elevation Myocardial Infarction. J Am Heart Assoc 2012; 1:e002246.
Thermodilution-derived coronary blood flow pattern immediately after coronary intervention as a predictor of microcirculatory damage and midterm clinical outcomes in patients with
Rioufol and Finet
JACC VOL. 64, NO. 18, 2014 NOVEMBER 4, 2014:1905–7
ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv 2014;7:149–55. 11. Fearon WF, Shah M, Ng M, et al. Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2008;51: 560–5. 12. Lim HS, Yoon MH, Tahk SJ, et al. Usefulness of the index of microcirculatory resistance for invasively assessing myocardial viability immediately after primary angioplasty for anterior myocardial infarction. Eur Heart J 2009; 30:2854–60.
Coronary Microcirculation in MI
13. Fearon WF, Low AF, Yong AS, et al. Prognostic value of the Index of Microcirculatory Resistance measured after primary percutaneous coronary intervention. Circulation 2013;127:2436–41. 14. Cuculi F, De Maria GL, Meier P, et al. Impact of microvascular obstruction on the assessment of
and infarct size. J Am Coll Cardiol 2000; 35:1162–9. 16. Feldman LJ, Coste P, Furber A, et al. FRench Optimal STenting-2 Invest. Incomplete resolution of ST-segment elevation is a marker of transient microcirculatory dysfunction after stenting for
coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction. J Am Coll Cardiol 2014;64:1894–904.
acute myocardial infarction. Circulation 2003;107: 2684–9.
15. Feldman LJ, Himbert D, Juliard JM, et al. Reperfusion syndrome: relationship of coronary blood flow reserve to left ventricular function
KEY WORDS acute myocardial infarction, index of microvascular resistance, myocardial microcirculation
1907
VOL. 64, NO. 18, 2014
ª 2014 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER INC.
http://dx.doi.org/10.1016/j.jacc.2014.08.028
EDITORIAL COMMENT
Invasive Coronary Microcirculation Assessment During Myocardial Infarction One Step Forward or Two Steps Back?* Gilles Rioufol, MD, PHD, Gérard Finet, MD, PHD
I
n acute coronary occlusion, ST-segment eleva-
(CFR) (5) and the index of microvascular resistance
tion myocardial infarction (STEMI) has been
(IMR) (6–10), making these promising candidates for
experimentally and clinically correlated with
assessing reperfusion lesions.
ischemic myocardial mass (area at risk), coronary
IMR has been of particular interest, as it shows less
reperfusion delay, and collateral circulation (1). Rapid
variation
coronary reperfusion, usually by primary percuta-
correlates with infarct size (6,7,10) and also with
neous coronary intervention (PPCI), provides the
improvement in left ventricular function (6–8,11,12).
principal means of limiting infarct size and improving
Recently, Fearon et al. (13) and Fukunaga et al. (10)
prognosis. It may, however, induce reperfusion
showed that IMR is a prognostic factor for heart
lesions, accounting for up to 40% to 50% of final
failure and death. When resistance is high, IMR
infarct size (2), making this a major research issue
increases and CFR decreases. IMR is typically <25 but
in therapeutic development (3). Much has been
may be double that in STEMI, with a cutoff between
learned thanks to cardiac magnetic resonance (CMR)
32 and 40 (6,9,10,12,13).
than
CFR
(11,12).
During
PPCI,
IMR
imaging, which notably enables noninvasive assess-
Whereas iterative measurements can be taken for
ment of the area at risk and reperfusion lesions
CMR (6,7), knowledge of microcirculation post-STEMI
(microvascular obstruction [MVO]) that develop in
using invasive IMR is usually limited to a single
the days after STEMI, and, later, specifics regarding
measurement taken at PPCI. Evolution and agree-
infarct size (4).
ment with CMR results, however, are essential to
In treating reperfusion lesions, however, the first minutes after coronary reperfusion are critical (1), thus making CMR ill-suited for detecting these lesions in acute MVO; consequently, other tools adapted for use in PPCI are now the focus of research and development.
improving understanding of the physiopathology of reperfusion lesions. SEE PAGE 1894
SERIAL PHYSIOLOGICAL MEASUREMENT AND CMR. From
this point of view, the study by Cuculi et al. (14) in
ENDOCORONARY PHYSIOLOGY TOOLS. Endocoro-
this issue of the Journal is exemplary. The authors
nary physiological measurements based on pressure
report follow-up of 82 acute STEMI patients in
wires could meet this aim. Presence and severity of
whom the culprit artery was studied on CFR, IMR,
MVO on CMR correlate with coronary flow reserve
and fractional flow reserve (FFR) both during PPCI and on post-intervention day 1 and month 6, with CMR measuring edema, MVO, and infarct size almost simultaneously during the 2 follow-up assessments.
*Editorials published in the Journal of the American College of Cardiology
The authors successfully met the challenge of
reflect the views of the authors and do not necessarily represent the
obtaining all of these measurements for almost half
views of JACC or the American College of Cardiology. From the Interventional Cardiology Department, Hospices Civils de Lyon, Claude Bernard University Lyon 1 and CARMEN INSERM 1060, Bron,
of the baseline population, with excellent reperfusion criteria making their findings easily generalizable.
France. Both authors have reported that they have no relationships
The 6-month lack of restenosis on angiography
relevant to the contents of this paper to disclose.
almost certainly rules out any focal epicardial
1906
Rioufol and Finet
JACC VOL. 64, NO. 18, 2014 NOVEMBER 4, 2014:1905–7
Coronary Microcirculation in MI
resistance effect, reinforcing the idea that analysis should focus on microcirculation. Ischemia duration
IMR
and area at risk on CMR, collaterality assessed on
100
MVO+ MVO-
**
*
90
FFR, MVO, and final infarct size were all measured,
NS (P=0.07)
80
providing data of virtually experimental quality.
70
We can draw a number of lessons from this study.
60
The first is that FFR evolves: in MVO without
**
**
50
epicardial stenosis, FFR diminishes significantly
40
over time. This reflects the epicardial resistance
30
induced by diffuse coronary atheroma seen in the
20
progressive normalization of residual hyperemia
10
capacity.
0
Evolution of IMR and CFR after PPCI is another interesting point, showing that microcirculation and its vasodilatory capacity begin to rally as of day 1,
ch
eo
G Mc
e
l. ta
)
f6
(re
o Yo
l. ta
)
f8
(re
e
l. ta
ne
Ah
with improvement continuing to 6 months, recov-
)
f9
(re
ga
na
ku Fu
l. ta
0)
f1
(re
e
ering normal values (IMR 24 22 and CFR 3.1 1.1).
F I G U R E 1 IMR Measurements in Literature According to
This evolution was already partially known for CFR
the Presence or Absence of MVO on Cardiac Magnetic
(15,16) but, although expected, had not been previ-
Resonance Imaging
ously demonstrated for IMR. This new work by Cuculi et al. (14), unlike earlier studies (6,8–10), found no difference in IMR according to presence/
4)
f1
(re
li e
cu
Cu
l. ta
Values are mean SD (except McGeoch et al. [6], which is median). IMR ¼ index of microvascular resistance; MVO ¼ microvascular obstruction. *p < 0.05. **p < 0.01.
absence of MVO (p ¼ 0.07) (Figure 1). However, while the presence of MVO in 47% of patients was associated with higher IMR and lower CFR, both nevertheless improved detection, reaching values
unsatisfactory way of identifying patients at high risk
comparable to those of patients free of MVO by
of MVO. Even so, invasive assessment remains an
6 months. Such variation and scatter in IMR values
important focus of research, as the moment of PPCI is
probably makes it unreliable as a substitute for
a unique opportunity for detecting reperfusion
CMR
lesions and setting up the therapeutic measures
in
assessing
reperfusion
lesion
severity,
although its prognostic value seems increasingly
needed to treat them.
confirmed (10,13). Thus, Cuculi et al. (14) are reporting important pathophysiologic
findings
that
bolster
our
un-
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
Gilles
Rioufol,
Cardiovascular
Hospital–Hospices
derstanding of microcirculation after myocardial
Civils de Lyon and INSERM 1060, Interventional
infarction. A single invasive measure of microcircu-
Cardiology, 28 Avenue Lépine, Bron, France 69677.
lation by IMR, CFR, or FFR thus now seems an
E-mail: [email protected].
REFERENCES 1. Ovize M, Thibault H, Przyklenk K. Myocardial conditioning: opportunities for clinical translation.
5. Hirsch A, Nijveldt R, Haeck JD, et al. Relation between the assessment of microvascular injury
8. Yoo SH, Yoo TK, Lim HS, Kim MY, Koh JH. Index of microcirculatory resistance as predictor for
Circ Res 2013;113:439–50.
by cardiovascular magnetic resonance and coronary Doppler flow velocity measurements in patients with acute anterior wall myocardial infarction. J Am Coll Cardiol 2008;51:2230–8.
microvascular functional recovery in patients with anterior myocardial infarction. J Korean Med Sci 2012;27:1044–50.
2. Fröhlich GM, Meier P, White SK, Yellon DM, Hausenloy DJ. Myocardial reperfusion injury: looking beyond primary PCI. Eur Heart J 2013; 34:1714–22. 3. Bekkers SC, Yazdani SK, Virmani R, Waltenberger J. Microvascular obstruction: underlying pathophysiology and clinical diagnosis. J Am Coll Cardiol 2010;55:1649–60.
6. McGeoch R, Watkins S, Berry C, et al. The index of microcirculatory resistance measured acutely predicts the extent and severity of myocardial infarction in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol Intv 2010;
9. Ahn SG, Lee SH, Lee JH, et al. Efficacy of combination treatment with intracoronary abciximab and aspiration thrombectomy on myocardial perfusion in patients with ST-segment elevation myocardial infarction undergoing primary coronary stenting. Yonsei Med J 2014;55:
4. Hundley WG, Bluemke DA, Finn JP, et al. ACCF/ ACR/AHA/NASCI/SCMR 2010 expert consensus
3:715–22.
606–16.
7. Payne AR, Berry C, Doolin O, et al. Microvas-
10. Fukunaga M, Fujii K, Kawasaki D, et al.
document on cardiovascular magnetic resonance: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J Am Coll Cardiol 2010;55:2614–62.
cular Resistance Predicts Myocardial Salvage and Infarct Characteristics in ST-segment elevation Myocardial Infarction. J Am Heart Assoc 2012; 1:e002246.
Thermodilution-derived coronary blood flow pattern immediately after coronary intervention as a predictor of microcirculatory damage and midterm clinical outcomes in patients with
Rioufol and Finet
JACC VOL. 64, NO. 18, 2014 NOVEMBER 4, 2014:1905–7
ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv 2014;7:149–55. 11. Fearon WF, Shah M, Ng M, et al. Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2008;51: 560–5. 12. Lim HS, Yoon MH, Tahk SJ, et al. Usefulness of the index of microcirculatory resistance for invasively assessing myocardial viability immediately after primary angioplasty for anterior myocardial infarction. Eur Heart J 2009; 30:2854–60.
Coronary Microcirculation in MI
13. Fearon WF, Low AF, Yong AS, et al. Prognostic value of the Index of Microcirculatory Resistance measured after primary percutaneous coronary intervention. Circulation 2013;127:2436–41. 14. Cuculi F, De Maria GL, Meier P, et al. Impact of microvascular obstruction on the assessment of
and infarct size. J Am Coll Cardiol 2000; 35:1162–9. 16. Feldman LJ, Coste P, Furber A, et al. FRench Optimal STenting-2 Invest. Incomplete resolution of ST-segment elevation is a marker of transient microcirculatory dysfunction after stenting for
coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction. J Am Coll Cardiol 2014;64:1894–904.
acute myocardial infarction. Circulation 2003;107: 2684–9.
15. Feldman LJ, Himbert D, Juliard JM, et al. Reperfusion syndrome: relationship of coronary blood flow reserve to left ventricular function
KEY WORDS acute myocardial infarction, index of microvascular resistance, myocardial microcirculation
1907