Gender-based acute outcome in percutaneous coronary intervention of chronic total coronary occlusion
Gender-based acute outcome in percutaneous coronary intervention of chronic total coronary occlusion
J. E. Guelker 0 1 2 3 4
L. Bansemir 0 1 2 3 4
R. Ott 0 1 2 3 4
K. Kuhr 0 1 2 3 4
B. Koektuerk 0 1 2 3 4
R. G. Turan 0 1 2 3 4
H. G. Klues 0 1 2 3 4
A. Bufe 0 1 2 3 4
0 Institute for Heart and Circulation Research, University Cologne , Cologne , Germany
1 Heart Centre Niederrhein, Department of Cardiology, Helios Clinic Krefeld , Krefeld , Germany
2 University of Witten/Herdecke , Witten , Germany
3 Department of Cardiology, Krankenhaus Porz am Rhein , Cologne , Germany
4 Institute of Medical Statistics , Informatics and Epidemiology , University Hospital of Cologne , Cologne , Germany
Background Percutaneous coronary intervention (PCI) of total chronic coronary occlusion (CTO) still remains a major challenge. Insignificant data are reported in the literature about gender differences in CTO-PCI in the era of new drug-eluting stents. In this study we analysed the impact of gender on procedural characteristics, complications and acute results. Methods Between 2010-2015 we included 780 consecutive patients. They underwent PCI for at least one CTO. Antegrade and retrograde CTO techniques were applied. Results Patients undergoing CTO-PCI were mainly men (84%). Male patients were younger (66.9 years ±10.6 vs. 61.1 years ±10.4; p < 0.001), more often smokers, but less frequently had a history of coronary artery disease (24.4% vs. 32.7%; p = 0.085) compared with female patients. Female patients more often had diabetes mellitus (29.6% vs. 26.7%; p = 0.55) and hypertension (82.7% vs. 80.7%; p = 0.55). There were no differences with respect to the amount of contrast fluid, fluoroscopy time and examination time as well as to the length of the stent or the number of the stents. The stent diameter was slightly smaller in women, which was not surprising because the lumen calibre tends to be smaller in women than in men (3.0 mm (2.5-3) vs. 3.0 mm (3-3.5); p < 0.001). The success rates were 81.0% in women and 80.1% in men. There was no significant interaction between gender and procedural success and complication rates. Conclusions Our retrospective study suggests that women and men have a comparable success rate at a low complication rate after recanalisation of CTO.
Coronary artery disease; Chronic total occlusion; Gender; Acute results
Recanalisation of total chronic coronary occlusion (CTO)
still remains a major challenge in interventional cardiology.
CTO is defined as a complete coronary artery occlusion
lasting longer than three months with thrombolysis in
myocardial infarction (TIMI) flow grade 0 . The prevalence
of CTO has been reported to be up to 30% among
patients with a clinical indication for coronary angiography
. Due to new interventional techniques and the use of
further advanced sophisticated materials, success rates of
CTO recanalisation have increased steadily in recent years.
In experienced hands reopening rates are more than 85%
. Percutaneous coronary intervention (PCI) of CTO is
a beneficial tool in coronary artery intervention; if
significant myocardial ischaemia is present and there are
clinical symptoms due to ischaemia, recanalisation is clearly
indicated. The left ventricular function can be improved,
more invasive therapies such as coronary artery bypass graft
(CABG) surgery can be avoided at lower complication rates
and even the prognosis of the disease can be improved in
suitable cases with a short-term and long-term survival
benefit [4, 5].
Only insignificant data are reported in the literature about
gender differences in CTO-PCI. The impact of gender on
outcome following CTO-PCI is not well defined. Only
outdated data have been published so far. It was reported that
the incidence of major adverse cardiac and cerebrovascular
events (MACCE) was increased in women compared with
men . However, the data were collected between 1998
and 2007 and since then the techniques and materials used
in the recanalisation of CTO have been substantially
extended and improved. We therefore reevaluated the issue of
the impact of gender on procedural characteristics,
complications and acute results following CTO-PCI for a cohort
of 780 patients between 2010 and 2015.
A total of 780 consecutive patients were included in this
study between 2010–2015. They underwent PCI for at least
one CTO in one high-volume centre with two experienced
operators. Indications for inclusion were angina pectoris
and/or a positive functional ischaemia test by magnetic
resonance imaging (MRI) or transthoracic echocardiography in
the territory of the occluded artery of more than 10%. Both
antegrade and retrograde CTO techniques were applied, and
the procedures were performed in a standardised manner.
Of the patients, 63% underwent a first-attempt CTO-PCI.
Without a prior angiogram it proved difficult to
determine the duration of the CTO. Then estimation of the
occlusion duration was based upon the first onset of angina or
dyspnoea. In some cases there was also a history of acute
myocardial infarction in the target vessel territory.
The mean Japanese Chronic Total Occlusion Score
(JCTO Score) was 2.8 and 2.9 respectively proving that
gender-related differences in CTO complexity did not exist. To
prevent thromboembolic complications, heparin was given
during the interventions guided by the activated clotting
time (>250 sec). All procedures were performed via both
the femoral arteries using 7-French guiding catheters; in
the majority of cases bilateral injections of contrast fluid
were given to determine the length of the lesion and the
existence and extent of intercoronary collaterals. Only
drugeluting stents were implanted. After PCI a dual antiplatelet
therapy consisting of 100 mg of aspirin once daily
indefinitely and 75 mg clopidogrel daily for at least 6 months
was continued. An Angio-Seal vascular closure device (St.
Jude Medical, USA) was used after the arterial puncture.
Procedural success was defined as successful
recanalisation of the CTO with residual stenosis <30% and
restoration of TIMI flow grade 3. A composite safety endpoint
summarising severe complications such as cardiovascular
mortality, vessel perforation, cardiac tamponade,
myocardial infarction and stroke was evaluated for each patient.
Continuous data are presented as the mean ± standard
deviation or as the median with the interquartile range;
categorical data are presented as numbers and percentages
unless otherwise specified. We used unpaired t tests for
parametric variables, Mann-Whitney U tests for
nonparametric variables, and Pearson’s chi-square tests for
categorical variables to perform pairwise comparisons by sex
and by PCI success for baseline and procedural
characteristics. The comparisons of patient groups with and without
PCI success were performed for all patients together and
in subgroups by sex. An unadjusted odds ratio (OR, female
vs. male) for success of the event PCI was estimated using
a univariable logistic regression model: a risk-adjusted OR
using a multivariable logistic regression model. Clinically
relevant patient characteristics showing a difference in
pairwise comparisons by sex (p-value <0.05) and remaining in
the model after a backward, stepwise selection procedure
were included in the final model. The variables considered
are given in Table 1.
For logistic regression models, ORs, corresponding 95%
confidence intervals and p-values (Wald test) are given.
All reported p-values are two-sided and p-values <0.05 are
regarded as statistically significant. Because the analyses
were regarded as explorative, we did not adjust for
multiple testing. Statistical analyses were performed using
IBMSPPS Statistics version 23 (Armonk, NY).
A robust back-up of the guiding catheter is a necessary
prerequisite for CTO-PCI. For the left coronary artery an
EBU catheter, for the right coronary artery either a JR4, an
IMA, a Multipurpose or an Amplatz catheter were applied.
The selection of coronary guide wires followed a
standardised concept of a ‘step-up’ guidewire strategy starting with
tapered polymer soft tip and ending up with super-stiff
guidewires (up to 12-g wires). For the selection of
microcatheters it is important that they have a low outer
diameter and allow wire manoeuvrability. Two kinds of
microcatheters were used: the Finecross microcatheter (Terumo,
Japan) for the antegrade approach, and the Corsair (Asahi
Intecc, Japan) microcatheter for the retrograde access.
CTO-PCI was started mostly on the antegrade route.
Bilateral contrast fluid injection allows to visualise the track
in detail, identify potential collaterals and guide the
proTable 1 Baseline and procedural characteristics by sex
Data presented as n (%), mean ± standard deviation or median
BMI body mass index, BMS bare metal stent, COPD chronic
obstructive pulmonary disease, DES drug-eluting stent, LAD left
anterior descending, LCX left circumflex, MI myocardial infarction,
PAD peripheral arterial disease, RCA right coronary artery
at test; bMann-Whitney U test; cPearson’s chi-square test
cess at any stage . At the beginning a soft tipped
tapered hydrophilic wire was used to identify microchannels
for entering and crossing the occlusion. The crossing
process was further supported by contrast fluid injections into
the proximal cap through the distal microcatheter . The
wire stiffness was increased stepwise. If the CTO could not
be crossed using the routine techniques, the parallel wire
technique, the see-saw wire technique, the anchor wire or
anchor balloon technique were applied [9, 10]. If required
the manoeuvres were guided by intravascular ultrasound
(IVUS) to understand the local anatomy and identify the
exact entry point of the CTO. The retrograde approach was
chosen if the antegrade approach failed .
The basis for the retrograde approach is septal and
epicardial coronary collaterals or bypass grafts. There is a huge
variety in the size, extent and anatomical course of the
septal collaterals. They may have a straight and visible
connection to the recipient vessel but in about 50% of the cases,
they do not provide access to the distal CTO segment. Many
collaterals are even angiographically invisible. For a
successful use their diameter and tortuosity are most
important. Techniques used for the retrograde approach were the
standard ‘true’ retrograde wire crossing, the kissing wire
technique, the controlled antegrade and retrograde tracking
(CART), and the reverse CART techniques with or without
a knuckle wire.
With the standard true retrograde technique, the
retrograde wire is advanced through the collaterals and the
lesion and threaded into the antegrade guide so that it could
be trapped in the antegrade guide. If this approach fails, the
kissing wire technique is the next choice; in this technique
the retrograde wire is advanced to the proximal part and
proximal cap within the lesion, then both the antegrade and
the retrograde wire can meet within the CTO lesion.
A further technique is the reverse CART technique. In
reverse CART a small balloon is inflated in the CTO over
an antegrade guidewire to create a subintimal or intimal
disruption and a connection with the retrograde guidewire,
which then facilitates the retrograde guidewire to pass into
the proximal true lumen . Here IVUS guidance using
an antegrade approach is often a helpful tool.
A ‘fully hybrid’ approach, which combines several
approaches such as the antegrade and retrograde, a wire
escalation strategy and a dissection-reentry, was not used in
this study .
Of the 780 patients, 126 (16%) were female and 654
(84%) male. Baseline and procedural characteristics of
both groups undergoing attempted CTO recanalisation are
summarised in Table 1.
Male patients were younger than women (61.1 ± 10.4
years vs. 66.9 ± 10.6 years; p < 0.001). With regard to
cardiovascular risk factors, men were more often smokers
(35.7% vs. 22.4%; p = 0.011), but less often had a history of
coronary artery disease (CAD) compared with female
patients (24.4% vs. 32.7%; p = 0.085) who suffered more from
diabetes mellitus (29.6% vs. 26.7%; p = 0.55) and atrial
hypertension (82.7% vs. 80.7%; p = 0.55). The length of the
occlusion was similar between the two groups (40 mm) but
women frequently had severe calcification of the CTO (69.0
vs. 64.5%; p = 0.33).
Women with a successful CTO recanalisation had a
comparable left ventricular ejection fraction (EF) (60.1 ± 9.6%
vs. 58.3 ± 9.1%; p = 0.39) and family history of CAD (27%
vs. 5%; p = 0.51) to female patients with a failed
procedure. Compared with those with an unsuccessful
intervention, men with a successful CTO-PCI less frequently had
a prior myocardial infarction (49.1% vs. 65.7%; p = 0.002),
a better ejection fraction (58.0 vs. 53.8%; p < 0.001) and
more often had a family history of CAD (26.5% vs. 16.0%;
p = 0.03).
There were no differences with respect to the amount
of contrast medium (250 ml (170–330) vs. 250 (200–350);
p = 0.22), fluoroscopy time (31.5 min (21–43) vs. 31.0 min
(21–46); p = 0.73) and examination time (90 min (60–120)
vs. 90 min (70–120); p = 0.638) as well as to the length
of the stent (63.5 vs. 62 mm; p = 0.5) or the number of
the stents (2 (2–3) vs. 2 (2–3); p = 0.705). The stent
diameter was slightly smaller in women (2.5–3.0 mm vs.
3.0–3.5 mm; p < 0.001) which was not surprising because
Fig. 1 Comparison of female and male patients regarding a success, b complications, c fluoroscopy time, d dose area product (FDP), e amount
of contrast medium, f examination time
Table 3 In-hospital clinical events
Female (n = 126)
Male (n = 654)
CABG coronary artery bypass graft
the lumen calibre tends to be smaller in women than in men
(Table 2; ).
The success rates were comparable in women and men.
A total of 81.0% of the women and 80.1% of the male
patients had a successful intervention, and the unadjusted OR
was 1.054 (95% CI 0.650 to 1.711; p = 0.830; female vs.
male). Age, smoking and ejection fraction were included
into the multivariable analysis. After model selection, only
ejection fraction remained in the model (OR 1.031, 95%
CI 1.013 to 1.049, p = 0.001); and the revealed
risk-adjusted OR for gender was 0.956 (95% CI 0.551 to 1.658,
p = 0.872). There were no differences in the selection of
materials used in women and men. In-hospital complication
rates were very low in both groups (8.4% vs. 8.1%; p = 0.9)
with no difference in statistical significance (Fig. 1). They
included mainly vascular complications such as haematoma
and cardiac tamponade which could be treated with a
pericardiocentesis and without severe consequences (Table 3).
The impact of gender referring to outcome in
cardiovascular diagnostic and therapeutic strategies has so far only been
fragmentarily evaluated. We report gender-based acute
outcome in a large consecutive series of patients undergoing
recanalisation of at least one CTO. Only 16% of the patients
were female but this is consistent with other trials
suggesting women are less likely to undergo treatment of CAD. We
did not find a significant difference in stent length, which
supports the data of Claessen et al. and Miyauchi et al. [6,
In previous PCI trials higher procedural mortality rates,
more strokes and higher vascular complications were
registered in women but newer data based on improved
techniques and advanced materials revealed that these
differences no longer exist [15–17]. Duvernoy et al. demonstrated
that the relationship between female gender and increased
risk of death and MACCE is no longer evident after elective
On the other hand the worse outcome of women after
CABG surgery compared with men makes it necessary
to provide alternatives if medically feasible [18–21]. Den
Ruijter et al. showed that women were more likely to
experience the composite endpoint including cardiovascular
death, myocardial infarction and stroke.
Particularly the fact that women have a higher
operative mortality then men after CABG surgery needs to bring
up new strategies . Blankstein et al. proved that
operative mortality for the entire population was 2.88% (women
4.24% vs. men 2.23%; p < 0.0001) and 22% higher in
women after a complete risk adjustment.
In contrast to these findings, we were able to show that
a complex interventional procedure such as CTO-PCI can
be performed safely in women with feasible acute results.
CTO-PCI not only improves survival and left ventricular
function but also gives freedom from angina pectoris and
reduces the need for CABG . Therefore, our data suggest
that revascularisation of CTO should probably be
considered more often as alternative treatment in women,
whenever it can be performed to avoid surgical treatment and to
achieve a complete revascularisation because we know that
females benefit from complete revascularisation equally to
Women are on average older than men when they first
undergo invasive cardiovascular procedures, presumably
because of the protective effects of oestrogen against coronary
atherosclerosis until menopause . Consistent to
previous studies the women in our study had a higher risk profile
for cardiovascular diseases. Only a minority of patients in
our study were female, which is comparable with the data of
the current literature and might be a hint that the screening
of patients with CAD between men and women is different.
Currently the lack of experienced operators and the low
reimbursement are the main obstacles for a change in
There are several limitations to our study. This is a
retrospective study, and the absolute figures in the section
’successful PCI vs. failed PCI in female patients’ are low,
all data were collected from a single centre. The results of
this study could be influenced by selection criteria, operator
experience, and varying techniques used by the operators.
Furthermore, there is no follow-up beyond the in-hospital
phase and some data concerning the cardiovascular risk,
such as cholesterol, kidney function or a prior stroke are
Our study, which included 780 patients, suggests that
women and men have a comparable success and
complication rate after recanalisation of CTO. These results
are contrary to gender-dependent comparisons of surgical
revascularisation strategies demonstrating a worse early
outcome with higher operative mortality in women
compared with men.
Conflict of interest J.E. Guelker, L. Bansemir, R. Ott, K. Kuhr,
B. Koektuerk, R.G. Turan, H.G. Klues, A. Bufe state that there are no
conflicts of interest.
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