Coronary physiology revisited
Coronary physiology revisited
J. J. Piek 0
0 Department of Cardiology, Academic Medical Centre , Amsterdam , The Netherlands
Coronary angiography is still the gold standard in the
diagnosis of coronary artery disease, although its limitations
in the assessment of haemodynamic severity of epicardial
stenosis are widely recognised [1, 2]. In the 1990s, these
limitations of angiography led to the introduction of
sensorequipped guidewires measuring pressure and flow to
optimise the diagnostic workup during cardiac catheterisation.
The most frequently used parameter is the fractional flow
reserve (FFR), defined as the ratio of the pressure distal to
a lesion relative to the aorta pressure during maximal
hyperaemia. The concept of FFR assumes a minimal influence of
the microvascular resistance during hyperaemic conditions,
although a large variability of microvascular resistance
exists even in patients with single vessel disease and a normal
left ventricular function . Moreover, this microvascular
resistance is also influenced by numerous other factors like
hypertension, diabetes, left ventricular hypertrophy and/or
diffuse coronary artery disease.
The assessment of coronary flow reserve, defined as the
ratio of the distal hyperaemic flow relative to baseline flow,
may serve as an alternative. However, an accurate
assessment of flow velocity is more cumbersome than FFR
measurement. Moreover, the use of coronary flow reserve has
also been criticised as it is determined by the resistance of
the epicardial narrowing as well as the distal
microvascular resistance and is therefore considered to be less
The FAME trials have shown the usefulness of FFR and
this parameter has emerged as a class I A indication for
clinical decision-making in the absence of documentation
of myocardial ischaemia. However, the use of FFR in
cardiac catheterisation laboratories did not increase as rapidly
as expected, despite its simplicity, which is partly explained
by the time-consuming approach of using intravenous
administration of hyperaemic agents. For this purpose, the
instantaneous wave-free ratio (iFR), which assesses the
diastolic pressure gradient during baseline conditions, was
introduced. The major advantage of this approach is that it
does not require hyperaemia and is therefore more suitable
for daily clinical practice.
Two large clinical trials, DEFINE-FLAIR and
SWEDEHEART, were designed as non-inferiority trials in a direct
comparison between iFR and FFR for patient management
using an iFR cut-off value of 0.89 and an FFR cut-off value
of 0.8 [4, 5]. Both studies came to the same conclusion: iFR
is non-inferior to FFR with respect to clinical outcome.
The expectation is that the simple approach of iFR
measurements will result in a warranted increase in the
number of physiological assessments during cardiac
catheterisation. This is important in view of the observed
alterations in diagnostic workup for patients selected for
coronary angiography. For the guidance of interventions, this
clinical decision-making of coronary intervention should
ideally be based upon an appropriate interpretation of the
patient’s complaints, the results of non-invasive diagnostic
stress tests, as well as the result of intracoronary
For many years now there has been a remarkable lack
of documentation in records of myocardial ischaemia prior
to cardiac catheterisation in daily clinical practice . To
guide coronary interventions in the absence of
documentation, an operator depends upon the interpretation of
complaints of the patients that are not always easy to judge, as
well as the use of intracoronary haemodynamic parameters.
The threshold for coronary angiography has been lowered
even further after the introduction of CT scans as an
alternative for the assessment of coronary artery disease and the
abundance of patients with troponin-T elevation not
associated with an acute coronary syndrome.
Against this background, it becomes more important to
refine the current intracoronary haemodynamic techniques.
Both iFR and FFR are pressure-derived parameters that are
attractive because of their simplicity, but that do not take
into account the complexity of coronary artery disease that
we are confronted with in our daily clinical practice. For
instance, the iFR does not require hyperaemia, but this
parameter is characterised by a wide grey zone (0.86–0.93).
For lesions within this grey zone it is advocated to use
FFR as a next step in the diagnostic workup . It is
debatable whether this is the best approach, as an abnormal
FFR (<0.80) may coincide with a normal coronary flow
reserve (>2.0) because of non-flow limiting lesions (20% of
the total amount of cases). These non-flow limiting lesions
are not causing myocardial ischaemia and the prognosis is
not distinctive from patients with normal haemodynamic
characteristics, i. e. a normal FFR and a normal coronary
flow reserve [8, 9]. Moreover, the use of combined
pressure flow measurements in borderline cases does not only
provide a coronary flow reserve, but it also generates a
hyperaemic stenosis resistance index that is even more specific
than FFR and coronary flow reserve .
The recognised shortcomings of pressure-derived
parameters have led to a revival of flow sensor technology that
is urgently needed to improve current intracoronary
diagnostic techniques. In this respect, it is important to note
that the patient, and not the diagnostic technique, should
be considered as the gold standard. This means that the
patient’s symptoms should improve if the diagnostic
technique indicates that a coronary intervention is justified and
the patient’s outcome should be safe if the test is normal.
The publication of the DEFINE-FLAIR and the
SWEDEHEART study is an essential step forward for the use of
coronary physiology during cardiac catheterisation, but
remember Churchill’s words: “Now, this is not the end. It is
not even the beginning of the end. But it is, perhaps, the
end of the beginning”.
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1. De Bruyne B , Pijls NH , Heyndrickx GR , et al. Pressure-derived fractional flow reserve to assess serial epicardial stenoses: theoretical basis and animal validation . Circulation . 2000 ; 101 ( 15 ): 1840 - 7 .
2. Piek JJ , Boersma E , di Mario C , et al. Angiographical and Doppler flow-derived parameters for assessment of coronary lesion severity and its relation to the result of exercise electrocardiography . DEBATE study group . Doppler Endpoints Balloon Angioplasty Trial Europe. Eur Heart J . 2000 ; 21 ( 6 ): 466 - 74 .
3. Meuwissen M , Chamuleau SAJ , Siebes M , et al. Role of variability in microvascular resistance on fractional flow reserve and coronary blood flow velocity reserve in intermediate coronary lesions . Circulation . 2001 ; 103 ( 2 ): 184 - 7 .
4. Davies JE , Dehbi HM , Al-Lamee R , et al. Use of the instantaneous wave-free ratio or fractional flow reserve in PCI . N Engl J Med . 2017 Epub ahead of print doi:10.1056/nejmoa1700445.
5. Gotberg M , Christiansen EH , Gudmundsdottir I , et al. Instantaneous wave-free ratio versus fractional flow reserve guided intervention (iFR-SWEDEHEART): rationale and design of a multicenter, prospective, registry-based randomized clinical trial . N Engl J Med . 2017 Epub ahead of print.
6. Kern MJ , Lerman A , Bech JW , et al. Physiological assessment of coronary artery disease in the cardiac catheterization laboratory: a scientific statement from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology . Circulation. 2006 ; 114 ( 12 ): 1321 - 41 .
7. Escaned J , Echavarria-Pinto M , Garcia-Garcia HM , et al. Prospective assessment of the diagnostic accuracy of instantaneous wavefree ratio to assess coronary stenosis relevance: results of ADVISE II international, multicenter study (ADenosine Vasodilator Independent Stenosis Evaluation II) . JACC Cardiovasc Interv . 2015 ; 8 ( 6 ): 824 - 33 .
8. Johnson NP , Kirkeeide RL , Gould KL . Is discordance of coronary flow reserve and fractional flow reserve due to methodology or clinically relevant coronary pathophysiology? JACC Cardiovasc Imaging . 2012 ; 5 ( 2 ): 193 - 202 .
9. van de Hoef TP , Echavarria-Pinto M , van Lavieren MA , et al. Diagnostic and prognostic implications of coronary flow capacity: a comprehensive cross-modality physiological concept in ischemic heart disease . JACC Cardiovasc Interv . 2015 ; 8 ( 13 ): 1670 - 80 .
10. Meuwissen M , Siebes M , Chamuleau SA , et al. Hyperemic stenosis resistance index for evaluation of functional coronary lesion severity . Circulation . 2002 ; 106 ( 4 ): 441 - 6 .