Gender-based acute outcome in percutaneous coronary intervention of chronic total coronary occlusion

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 [1]. The prevalence of CTO has been reported to be up to 30% among patients with a clinical indication for coronary angiography [2]. 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% [3]. 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 Only outdated data have been published so far.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 [6]. 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 (J-CTO 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 drug-eluting 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.

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 the lumen calibre tends to be smaller in women than in men (Table 2; [14]).

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, 24].

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 PCI.

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 [22]. 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 [23]. 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 males [24].

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 [25]. 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 strategy.

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.