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Functional imaging for suspected CHD can help avoid angiography
Initial investigation of patients with suspected coronary heart disease using functional imaging rather than guideline-directed care resulted in significantly
less unnecessary angiography, outcome of the Clinical Evaluation of MAgnetic Resonance imaging in Coronary heart disease 2 (CE-MARC 2) study shows.
J
ohn Greenwood, PhD, of the University of Leeds, UK,
said that the findings could exert an important impact
on referral rates for invasive coronary angiography, and
potentially healthcare costs.
“Rates of invasive angiography are considered too high among
patients with suspected coronary heart disease,” he said. “Our
findings show that both cardiovascular magnetic resonance and
myocardial perfusion scintigraphy significantly reduced rates of
unnecessary angiography compared to guideline-directed care,
with no penalty in terms of major adverse cardiovascular events.
This suggests that functional imaging should be adopted on a
wider basis, even in high-risk patient subgroups.”
CE-MARC 2 included 1202 patients with suspected
coronary heart disease from six UK centres. Patients were
randomised to functional imaging-based investigation with
either cardiovascular magnetic resonance (n=481), myocardial
perfusion scintigraphy (n=481), or guideline-directed inves-
tigation (n=240) based on National Institute for Health and
Care Excellence (NICE) guidelines.
In the latter group, those with a pre-test likelihood of
10–29% (low risk for coronary heart disease based on age,
gender, symptom characteristics, and clinical history) were
scheduled for cardiac computed tomography. Those with a
pre-test likelihood of 30% to 60% (intermediate risk) were
scheduled for myocardial perfusion scintigraphy, and those
with a high pre-test likelihood were sent directly to coronary
angiography.
The primary endpoint was unnecessary coronary angiogra-
phy within 12 months, defined by the absence of significant
stenosis as measured by fractional flow reserve or quantitative
coronary angiography, with secondary endpoints of major ad-
verse cardiovascular events, and positive angiography within
this same time period.
Twenty-two percent of the study population underwent
coronary angiography within 12 months, with unnecessary
angiography performed in 28.8% of the NICE guidelines
group, 7.5% of the cardiovascular magnetic resonance group,
and 7.1% of the myocardial perfusion scintigraphy group.
The adjusted odds ratio of unnecessary angiography for the
cardiovascular magnetic resonance group vs the NICE guide-
lines group was 0.21 (95% confidence interval 0.12–0.34; P <
0.001), with no statistically significant difference between the
cardiovascular magnetic resonance and myocardial perfusion
scintigraphy groups.
Among the three strategies, there was no difference in short-
term major adverse cardiovascular events or posi-
tive angiography rates.
Dr Greenwood noted, “Worldwide, myocardial
perfusion scintigraphy is the most commonly
used test to assess suspected coronary heart
disease, but cardiovascular magnetic resonance
is increasingly recognised as conferring high di-
agnostic accuracy and prognostic value. Though
the results of CE-MARC 2 showed no difference
between the cardiovascular magnetic resonance
and myocardial perfusion scintigraphy strate-
gies in terms of unnecessary angiography rates,
our original, 2012 CE-MARC study showed
that cardiovascular magnetic resonance yielded
higher diagnostic accuracy than myocardial per-
fusion scintigraphy, and, as published in 2016,
as a stronger predictor of risk of major adverse
cardiovascular events.”
Dr Greenwood concluded, “These results show
that broader use of functional imaging (cardiovas-
cular magnetic resonance or myocardial perfusion
scintigraphy), in low-, intermediate-, and high-risk
patient groups, could reduce rates of invasive
angiography that ultimately shows no obstructive
coronary disease. In addition, CE-MARC and CE-
MARC 2 further support cardiovascular magnetic
resonance as an alternative to myocardial perfusion
scintigraphy for the diagnosis and management of
patients with suspected coronary heart disease.”
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Lipoprotein(a) apheresis proves beneficial in refractory angina
Lipoprotein apheresis, a
therapy normally used to fil-
ter excess cholesterol from
the blood of patients with fa-
milial hypercholesterolemia,
may play a role in patients
with refractory angina,
reports a prospective, ran-
domised, sham-controlled,
blinded, crossover study.
T
ina Khan, MRCP, of Impe-
rial College, London, UK,
explained that the extracorpor-
eal treatment resulted in significant
improvement over sham therapy in
patients with refractory angina and
raised levels of lipoprotein(a).
“Angina refractory to both medical
therapy and revascularisation is a de-
bilitating condition that is increasing
in frequency, and there is a pressing
need for novel treatments for these
patients. Such patients continue
to suffer with troublesome angina
despite optimal medical therapy, as
well as surgical and/or percutaneous
coronary revascularisation. Treat-
ment options are limited,” she said.
“Our trial provided the first
evidence that lipoprotein apheresis
leads to improvement among these
patients in the primary endpoint of
myocardial blood flow, as measured
by myocardial perfusion reserve, as
well as the secondary endpoints of
exercise capacity, angina symptoms,
quality of life, and atheroma burden.
This treatment approach could im-
prove the cardiac health and lives of
such patients.”
Lipoprotein(a) is similar in
structure to low density lipoprotein
cholesterol, except for an additional,
attached protein-apolipoprotein(a).
Raised lipoprotein(a) is a strong risk
factor for coronary heart disease and
may be prevalent in patients with
refractory angina.
Studies suggest that elevated
lipoprotein(a) may promote ath-
erosclerosis and reduce myocardial
perfusion, but no effective pharma-
cologic treatment is yet approved to
treat elevated lipoprotein(a). Elevat-
ed lipoprotein(a) is essentially resist-
ant to conventional lipid-lowering
treatment with statins. Dr Khan
and colleagues have now shown
that lipoprotein(a) can effectively be
lowered with lipoprotein apheresis.
The apheresis study included 20
patients with refractory angina and
elevated lipoprotein(a) levels above
500 mg/L. Patients were randomised
to weekly lipoprotein apheresis or a
sham procedure for 3 months, then
crossed over for another 3 months,
with a 1-month washout period be-
tween the two.
The primary outcome, measured
with cardiac magnetic resonance
imaging, was myocardial perfusion
reserve, which is the ratio of myocar-
dial blood flow at stress vs rest after
3 months of lipoprotein apheresis,
compared to baseline.
A significant increase of 0.63 in
myocardial perfusion reserve was
observed after apheresis treatment
vs sham (P < 0.001). Specifically,
myocardial perfusion reserve in-
creased from 1.45 to 1.93 with
apheresis, and did not change sig-
nificantly after sham.
Secondary endpoints of carotid
wall volume and distensibility also
improved after apheresis, as did
exercise capacity, symptoms of
angina, and quality of life scores.
These parameters did not improve
after sham.
Significant symptom improve-
ment was observed after apheresis
but not after sham in four of five
domains in the SeattleAngina Ques-
tionnaire, including:
•
Physical limitation score (median
change of 27.8 vs –4.2)
•
Angina stability score (mean
change of 17.5 vs –3.75)
•
Angina frequency score (mean
change of 35.0 vs –5.0)
•
Quality of life score (mean change
of 25.8 vs 4.6)
In the fifth domain, SeattleAngina
Questionnaire treatment satisfac-
tion score improved slightly, by 6.25,
during apheresis vs 0.0 or no change
during sham administration. Simi-
larly, physical component scores of
quality of life assessed by the Short
Form-36 Questionnaire also im-
proved significantly after apheresis
but not sham administration.
Dr Khan concluded, “Our study
was the first randomised controlled
trial to assess the impact of lipopro-
tein apheresis in patients with refrac-
tory angina and raised lipoprotein(a),
in the absence of significantly raised
low density lipoprotein cholesterol.
“Findings suggest that lipopro-
tein apheresis provides significant
clinical benefit to patients with
refractory angina in the context of
raised lipoprotein(a). The outcome
represents a much needed novel
treatment option for this therapeu-
tically challenging patient cohort.”
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