Clinical characteristics of patients with suspected cardiac chest pain and angiographically normal coronary arteries in a secondary care hospital
Clinical characteristics of patients with suspected cardiac chest pain and angiographically normal coronary arteries in a secondary care hospital
T. S. de Lange 0 1 2
R. Y. G Tijssen 0 1 2
P. Damman 0 1 2
P. F. M. M. van Bergen 0 1 2
0 Heart Center, Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands
1 Department of Cardiology , Westfriesgasthuis, Hoorn , The Netherlands
2 P. F. M. M. van Bergen
Background An important number of patients with suspected cardiac chest pain have non-obstructive coronary artery disease. Our purpose was to describe the clinical characteristics of patients with normal or near-normal coronary arteries in routine cardiological practice in a secondary care hospital. Methods In 2013, consecutive patients referred for invasive coronary angiography with suspected cardiac chest pain were analysed at a single-centre (Westfriesgasthuis, Hoorn, the Netherlands). Coronary arteries were defined as normal or near-normal if they showed no stenosis or only slight wall irregularities on visual assessment. Patients with a final non-cardiac diagnosis for the chest pain were excluded. Results A total of 558 patients were included. Of these, 151 (27%) showed normal or near-normal coronary arteries on visual assessment. This group of patients were significantly more often female (p < 0.001), younger (p < 0.001) and non-diabetic (p = 0.002). Forty percent of hospitalised patients who had normal or near-normal coronary arteries at coronary angiography showed an elevated troponin. Conclusion In routine cardiological practice, around 1 out of 4 patients with suspected cardiac chest pain undergoing invasive angiography had normal or near-normal coronary arteries. We suggest that premenopausal women with suspected cardiac chest pain could be considered for noninvasive coronary imaging as a first step in clinical practice.
Chest pain; Normal coronary arteries; Troponin
Stable angina pectoris and acute coronary syndrome (ACS)
are two clinical manifestations of coronary artery disease
(CAD). In accordance with clinical practice guidelines,
most of these patients are referred for intracoronary
evaluation [1–3]. Previous studies show that approximately 10%
of non-ST-elevation myocardial infarction (non-STEMI)
patients and 30–60% of patients with stable AP have no
CAD [4–8]. Moreover, other studies and registries have
shown that up to 39% of patients with suspected CAD may
have visually normal or near-normal coronary arteries on
invasive coronary angiography [9, 10]. More recently,
noninvasive imaging techniques have confirmed that about half
of patients with a clinical indication for CAD evaluation
had no apparent coronary disease [11–13]. However, recent
data on normal coronary arteries in invasive angiography
in contemporary routine cardiological practice are lacking.
In this paper we describe the clinical characteristics of
consecutive patients with normal coronary arteries at invasive
coronary angiography for suspected cardiac chest pain at
a secondary care centre.
The study population consisted of patients who were
referred for coronary angiography because of suspected
cardiac chest pain between January 1, 2013 and January 1,
2014 at the Westfriesgasthuis, a medium large secondary
care centre in Hoorn, the Netherlands. Patients with STEMI
were excluded because they were directly referred to a
primary PCI centre . Peri-procedural patient
characteristics, laboratory results, ECGs and data from coronary
angiograms were collected retrospectively. This study
complies with the Dutch Medical Research Involving Human
Based on the results of the coronary angiogram, patients
were classified into two groups: 1) patients with visually
normal or only minimal coronary artery stenosis, and 2)
patients with more extensive coronary disease. The extent and
severity of CAD was assessed by routine visual assessment
by the operator. Patients were diagnosed with stable angina,
unstable angina or non-STEMI based on clinical data [1–3].
One-year outcomes included coronary revascularisation by
either PCI or CABG, and survival during follow-up.
Outcomes were collected from electronic patient files.
Continuous variables were expressed as mean ± standard
deviation and categorical data were expressed as numbers
(percentage). Differences between patient groups were
analysed with a chi-square or a Fisher’s exact test for
categorical variables and independent samples t-test for continuous
variables; two-sided probability of less than 0.05 was
considered statistically significant. Multivariate analysis was
performed using binary logistic regression. Data were
analysed using IBM SPSS statistics for Windows version 19.0
(IBM Corp., Armonk NY).
Between January 1, 2013 and January 1, 2014, a total of 817
patients underwent invasive coronary angiography (Fig. 1)
of whom 577 (71%) underwent coronary angiography
because of suspected cardiac chest pain. During one-year
follow-up, 19 patients were excluded because of a definitive
non-coronary diagnosis of their chest pain. Consequently,
558 patients were analysed; 151 patients had normal or
817 patients underwent cardiac
catheterisation in 2013
9 patients with insufficient information available
231 patients with indications other than chest pain prior to
577 patients underwent cardiac
catheterisation because of chest pain
558 patients included
407 patients with more extensive coronary stenosis
151 patients with angiographic visually normal or
nearnormal coronary arteries (study population)
Fig. 1 Flowchart
near-normal coronary arteries, and 407 patients had more
extensive CAD (Fig. 1).
Baseline characteristics and 1-year outcomes of the two
patient groups are shown in Table 1. Patients with
visually normal arteries showed significant differences
compared with patients with more extensive coronary disease
with regard to age (62.6 vs 66.7 years, p < 0.001), female
gender (54% vs 27%, p < 0.001) and diabetes (11% vs
23%, p = 0.002). Consequent multivariate analysis showed
that on coronary angiography lower age, female gender and
absence of diabetes were independent predictors of normal
Table 2 shows the results according to defined
clinical diagnosis in both patient groups. All three diagnostic
categories encompassed a substantial number of patients
with normal or near-normal coronary arteries,
predominantly women. None of the patients in the normal coronary
artery group had a coronary revascularisation procedure
during follow-up versus 30% in the coronary artery
stenosis group. Furthermore, one-year survival rate was 99.3%
in the normal coronary artery group and 95.8% in the group
of patients with coronary stenosis. The cause of death of
the deceased patient in the normal coronary artery group
was non-cardiac disease.
BMI body mass index, CAD coronary artery disease
a Troponin T > 0.013 μg/L with a significant increase in the second value
Patients with unstable AP and non-STEMI were all hospitalised
This study shows that approximately 1 out of 4 patients
with suspected cardiac chest pain in routine cardiological
practice in a secondary care hospital has visually normal
coronary arteries on invasive coronary angiography and that
these patients are younger, more often female and
nondiabetic than patients with more extensive CAD.
Suspected cardiac chest pain andnormal or
nearnormal coronary arteries
Several studies have previously reported on patients with
suspected cardiac chest pain and normal coronary
arteries on invasive coronary angiogram [9, 14–16]. Normal
coronary arteries, showing no apparent CAD, are
associated with a significantly lower 1-year risk of myocardial
infarction (MI) and all-cause mortality compared with
nonobstructive CAD . Our results confirm that the
prognosis is better in patients with minimal CAD than in
patients with more extensive CAD. More recently, studies
using a non-invasive imaging technique such as coronary
computed tomography angiography ormyocardial perfusion
imaging have confirmed both normal coronary arteries and
non-obstructive coronary disease in patients with suspected
CAD, with an impaired prognosis in patients with
increasing severity of coronary disease [13, 17–22].
Possible causes of chest pain in patients with normal
coronary arteries are numerous and include plaque erosion,
coronary microvascular disease, endothelial dysfunction,
myocardial bridging and coronary artery spasm [23–25].
Forty percent of hospitalised patients with normal coronary
arteries in our study population had a clinically significant
rise in troponin, indicating myocardial infarction. Earlier
studies showed that a prolonged episode of coronary artery
spasm can lead to elevated troponin and myocardial
infarction [26–28]. Although coronary spasm is sometimes
believed to be restricted to Asian patients [29–31], the
coronary artery spasm in patients with acute coronary syndrome
study (CASPAR) shows that coronary spasm can be a
frequent cause of ACS in a European population with an
excellent prognosis for survival and coronary events after three
years [32, 33].
Previous studies have shown that chest pain syndromes are
more common in women than in men and are less related to
the presence of atherosclerosis in the large epicardial
coronary arteries [17, 34–37]. Gender-specific factors that affect
the development and prognosis of coronary heart disease are
diverse but are becoming increasingly clear [38, 39]. Our
multivariate analysis confirmed that female gender itself
was independently associated with normal coronary
arteries in our patients with suspected CAD. Yet, most of the
female patients with normal coronary arteries in our
patient population were hospitalised for unstable AP or
nonSTEMI, suggestive of a temporary – but haemodynamically
relevant – coronary obstruction.
Vasospasm of the epicardial arteries, microvascular
coronary dysfunction (non-endothelial dependent), endothelial
dysfunction and higher endothelial shear may all attribute
to the higher prevalence of angina and adverse
cardiovascular events in women compared with men [40–42]. Our data
show that the 1-year prognosis for patients with suspected
CAD and normal coronary arteries is good for both men
Implications for clinical practice
Recent data show that cardiac MRI or Myocardial Perfusion
Imaging (MPI) can help to reduce the use of coronary
angiography in a general population of patients with suspected
CAD . Our data show that younger premenopausal
women with suspected chest pain could be considered for
non-invasive coronary imaging as a first step in the
Strengths and limitations of this study
This study included consecutive patients undergoing
invasive angiography at a non-intervention centre, therefore
no additional intracoronary evaluation such as
intravascular ultrasound (IVUS) or optical coherence tomography
(OCT), could be performed to assess angiographic
nonvisible atherosclerosis and plaque erosion. Neither could
we establish functional coronary disease due to thelack of
a spasm provocation test facility at our hospital.
Also, the introduction of highly sensitive troponin
assays has improved the accuracy of diagnostic testing for
myocardial necrosis and thereby increased the number of
patients referred for additional intracoronary examination,
in particular in women [44–46]. However, this study
reflects a real-life cohort of patients with stable AP or ACS
in a secondary care hospital using establised care protocols
according to the latest clinical practice guidelines.
This study demonstrates a high prevalence of normal or
near-normal coronary arteries in patients with suspected
cardiac chest pain in routine cardiological practice in a
secondary care hospital today. These patients were more often
female, younger or non-diabetic and had excellent 1-year
survival rate and coronary revascularisation rate
Consequently, we suggest that premenopausal females
who have suspected CAD could be considered for
noninvasive cardiac imaging as a first step in clinical practice.
Funding This study was not funded.
Conflict of interest T.S. de Lange, R.Y.G. Tijssen, P. Damman and
P.F.M.M. van Bergen declare that they have no competing interests.
Open Access This article is distributed under the terms of the
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creativecommons.org/licenses/by/4.0/), which permits unrestricted
use, distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
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