Access to side branches with a sharply angulated origin: usefulness of a specific wire for chronic occlusions

Introduction

At times, using intracoronary guides to access sharply angulated lateral branches with a lesion that requires protection when treating bifurcations is extremely difficult. There is not too much information in the medical literature on the number of branches that cannot be accessed, but experienced groups say that the rate is around 3%1. Accessing the lateral branch is usually easy when the angle between the main branch and the lateral branch is < 70°, more difficult with distal bifurcation angles > 70º, and especially difficult with angles > 90°.

Different techniques and devices have been designed such as angulated microcatheters, double-lumen catheters2 or deflectable catheters2 o defectables3,4, which, combined with the use of hydrophilic guidewires allow us to be able to perform procedures. However, even when access has not occurred, the prolapse of the guidewire towards the main branch is a common thing when advancing the guidewire or the microcatheter, especially when dealing with sharp angles and large caliber main branches.

We hereby present a way to conduct this kind of procedure using a specific chronic occlusion guidewire that combines excellent maneuverability with great support in its distal edge to avoid prolapse. Additionally, we will be reviewing the different techniques and devices available today to perform these procedures.

Methods

Between January 2017 and October 2018, we analyzed patients with an indication for percutaneous intervention in their lateral branches or branches requiring a second guidewire when treating a bifurcation whose origin had a ≥ 80° angle through visual assessment. In all cases, the initial strategy was to use one Caravel microcatheter (Asahi, Japan) with the Sion and Fielder XT guidewires followed by the Stride angulated microcatheter (Teleflex, United States) or the Crusade double-lumen microcatheter (Kaneka, Japan).

In those cases where the guidewire advanced successfully with such devices, the Gaia First guidewire (Asahi, Japan) with the Caravel microcatheter was used. This guidewire was picked because of its excellent maneuverability, capacity to maintain the shape of its distal edge and the support granted by its distal segment. The characteristics of the procedures conducted with the Gaia First guidewire as well as the properties of this guide are described here because, in our opinion, they can be of great help in these cases.

Results

During the entire period of the study, 1342 percutaneous coronary interventions (PCIs) were conducted at our center, and in 52 (3.8%) of them, the lesion was found in a lateral branch whose origin had a ≥ 80° angle or was a bifurcation with an oversized lateral branch and the mentioned exit angle. In nine patients we were not able to access the lateral branch using the Sion or the Fielder XT guidewires and straight, angulated, or double-lumen microcatheters; in three cases it was due to the fact that we could not access using the guidewire distal edge, and in the remaining six because the main vessel prolapsed when trying to advance the guidewire or the microcatheter. All procedures were conducted using 6-Fr catheters, eight of them using the radial approach and the remaining one using the femoral approach. Table 1 shows the characteristics of the different cases.

Table 1. Characteristics of patients and lesions

The last step that was successful in all the patients consisted of using the Caravel straight microcatheter and the Gaia First guidewire after modifying the shape of the tip to make it match the angle of the vessel (figure 1). Thanks to its excellent maneuverability and the support granted by its distal edge, this guidewire allows easy access to the vessel and facilitates the advance of the microcatheter so that we can change this guide by another guidewire with a softer tip. No coronary dissections, or vessel occlusions were reported, and all procedures were completed with optimal results.

Figure 1. Modification of the Gaia First guidewire tip.

Video 1 of the supplementary data shows a case with a sharply angulated origin in a dominant circumflex artery of a very high-risk patient with a 25% ejection fraction who suffered from an anterior infarction back in 2002. The left anterior descending artery had a chronic occlusion of 50 mm in length with a scab in its anterior side. The procedure was conducted using the Impella CP ventricular assist device (Abiomed, United States) and the circumflex artery was accessed using the Gaia First guidewire and the aforementioned technique after trying the Sion and Fielder XT guidewires and one angulated microcatheter. Two 2 × 15 mm Resolute Onix stents (Medtronic, United States) were implanted at the beginning of the circumflex artery with optimal angiographic results (video 2 of the supplementary data). The patient was discharged three days after the uneventful implantation of a triple chamber defibrillator.

Figure 2 and figure 3 show two cases with double angulation with unsuccessful access using conventional guidewires; and figure 4 and figure 5, show two cases where the problem was the prolapse of the tip of the guidewire when trying to advance the guidewire or the microcatheter.

Figure 2. Access to the distal anterior descending artery, with a severe lesion, double angulation and diagonal bifurcation in the middle segment. Filed access with conventional guidewires and microcatheters.

Figure 3. Access to the distal circumflex artery with double bifurcation and double angulation in the middle segment. Failed access with conventional guidewires and microcatheters.

Figure 4. Access to the second marginal obtuse artery with double angulation. It was accessed using a conventional guidewire but repeated prolapse occurred when trying to advance the guidewire.

Figure 5. Access to the diagonal with angulated origin. It was accessed using a conventional guidewire but repeated prolapse occurred when trying to advance the guidewire.

Discussion

Accessing sharply angulated lateral branches with intracoronary guidewires can be difficult. To be able to solve this problem, several options5, have been described, among these, shaping the curvature of the tip of the guidewire, using guidewires with hydrophilic or more rigid polymeric coating, the double guidewire technique, inflating the balloon inside the main branch to modify the access, and use microcatheters with different designs (angulated, double-lumen, or deflectable).

The tip of the guidewire should have an adequate shape to facilitate access to the lateral branch. The curves typically used to access bifurcations are basically four: one single curve with a short tip (2-3 mm), one single curve with a long tip (4-6 mm), one single curve without rough angulation, and a double curve6. The latter are the most suitable shapes in cases of sharp angulations.

This study details the use of a guidewire designed for chronic occlusions7 and facilitate access to sharply angulated branches. The Gaia First guidewire, same as it happens with the Gaia Second and Third guidewires was first introduced into the market back in 2014. Seventeen years after its manufacturer, Asahi, would develop the very first prototype of specific guidewires for the management of chronic occlusions, the Miracle guidewire. Its design includes the 400 mm long SLIP-COAT coating that improves maneuverability inside the microcatheter with a distal coil structure of 150 mm, a 0.010” diameter and a load of 1.7 g on the tip. Such a design enables an excellent 1:1 capacity of manipulation which, in turn, helps maneuver the guidewire under optimal conditions. Although it was designed for the management of chronic occlusions, its perfect maneuverability of the tip added to how rigid the 150 mm distal segment is, and its capacity to maintain the shape of the tip make it an excellent guidewire for the access of sharply angulated branches granting the right support for the advancement of the microcatheter. We think it is important to say that this strategy used as a fist choice strategy after the hydrophilic guidewire has failed added to a straight microcatheter, can be very attractive financially since we do not need to use any additional curved, double-lumen, or deflectable microcatheters. However, we should not forget that although no complications were reported in the series described, the number of cases is limited and we always have to bear in mind that, even though it is a guidewire of limited lightweight and excellent maneuverability, it was designed for the management of chronic occlusions, so it should be used with care due to the theoretical risk of dissection or occlusion of the blood vessel.

There are other guidewires specifically designed for this type of lesions such as the Sion Black (Asahi, Japan), but, since this guidewire was not used in the lesions presented in this series, we cannot give any information on how it may behave in cases like the one presented here. Also, it is very difficult to have access to all the guidewires available in the market today and the goal of this study was to give an alternative solution when the first intention guidewires fail.

Another technique is the retrograde access to the lateral branch by giving the lateral branch guidewire much more curvature and trying to access the branch when the guidewire has been removed8. This is a sophisticated technique when using doublelumen microcatheters since we insert one hydrophilic guidewire whose very curved distal edge stands out through the lateral orifice of the microcatheter2,9-12. The idea is almost the same, to advance the double-lumen catheter over the guidewire located in the monorail compartment while the guidewire tries to access the lateral branch located in the coaxial compartment and standing out 5 mm to 10 mm through the lateral orifice and with the curve oriented almost 180º with respect to the main vessel. This way, when removing the microcatheter, we should be able to access the lateral branch using the bent guidewire.

We can also use the Venture deflectable catheter (Teleflex, United States) -compatible with e 6-Fr guidewire catheter- available in coaxial and monorail design, that allows us to use any 0.014” coronary guidewires.4,13. The 8 mm distal tip is radiopaque and it can bend up to 90º rotated with clockwise torque in the catheter proximal area. In order to avoid any traumas, it is advanced towards the lesion over a guidewire in straight position and, once the point of interest has been reached, the tip starts to bend until it reaches the target angle. This deflection capability added to the possibility of turning the tip of the catheter in a circumferential plane, allows us to direct the guidewire and, once it has passed, rotate it in the counterclockwise direction to make the catheter return to its straight position and then be able to remove it.3. The rate of success when accessing lateral branches is said to be close to 80%-85%3,4, and the rigidity of the tip requires being extremely careful to limit the possibility of traumatizing the vessel. A few cases of destructured guidewire due to over-manipulation have been reported.

Finally, it has also been suggested that we should inflate a balloon inside the bifurcation in order to change the plaque and allow access to the branch14, but this solution should only be used when the other solutions have failed because, although it is easy to do, previous dilatations can cause changes in the plaque and eventually lead to occluding the branch15.

Conclusions

Accessing sharply angulated lateral branches is very hard to do with the guidewire, at times, because the access site will not allow it, or due to posterior prolapse towards the main vessel. On top of angulated, double-lumen, or deflectable microcatheters with routine guidewires, these procedures can be performed easily using a specific guidewire for the management of chronic occlusions that combines the excellent maneuverability of the tip and support of the distal edge which facilitates the advancement of the straight microcatheter to later change the guidewire for another guidewire with a softer distal edge.

Conflicts of interests

No conflicts of interest declared whatsoever.

References

Introduction

Percutaneous coronary intervention (PCI) is the treatment of choice for the management of ST-segment elevation myocardial infarction (STEMI). First-generation drug-eluting stents (DES) reduced restenosis and the need for reinterventions compared to bare-metal stents (BMS)1,2. However, the higher incidence rates of late thrombosis3, mortality and infarction4 ueled controversy over the implementation of these devices in patients with STEMI, a population with an identified increased risk of stent thrombosis5.

Second-generation DES with thinner struts, biocompatible poly-mers, and thromboresistant properties proved to be safe and more effective than first-generation DES and traditional BMS, particularly with significant reductions in angiographic restenosis and unplanned revascularizations of the target injury or culprit artery.6. The actual clinical guidelines for the management of STEMI recommend the use of new-generation DES7.

In a combined analysis of the EXAMINATION and COMFORTABLEAMI clinical trials that compared new-generation DES versus BMS, the use of a DES was associated with increased safety and efficacy at 1 year8. In the 2-year follow-up of patients included in the COMFORTABLE-AMI trial, the use of DES was associated with a reduction in a composite of all-cause mortality, follow-up myocardial infarction, and new revascularizations9. The results of the 5-year follow-up of the EXAMINATION10, that compared an everolimus-eluting stent to a BMS showed that the new-generation DES was associated with more survival and less myocardial infarctions at follow-up6.

Our goal was to analyze the long-term prognostic impact of newgeneration DES in a real-world population of patients with STEMI.

Methods

Study population

This is a retrospective observational study that included (n = 1499) all consecutive patients admitted due to STEMI who underwent primary percutaneous interventions (PCI) at our center between January 2008 and December 2015. The patients who were not implanted with a stent during the percutaneous coronary intervention (PCI) (n = 131) and those implanted with a bioabsorbable scaffold (n = 11) were excluded. In 24.9% of patients (n = 374), the PCI was conducted with DES implantation in the infarctrelated artery.

The PCI was conducted following the guidelines from the European Society of Cardiology7,11 and the decision to implant a DES or a BMS was left to the attending interventional cardiologist clinical criteria. Antiplatelet therapy consisted of acetylsalicylic acid and a P2Y₁₂ inhibitor (clopidogrel during the early years and ticagrelor, and prasugrel more recently).

Demographic, clinical, echocardiographic, coronary angiography and laboratory data were collected by cardiologists in a computerized database. Both the material used during the PCI and the characteristics of the procedure were included at the time of the PCI by the specialist in hemodynamics and the attending operator. The structured follow-up was conducted using the IANUS electronic health record system (the only one available and mandatory in Galicia, Spain). Events were independently adjudicated by 2 independent cardiologists and when they disagreed, by a third cardiologist.

Definitions

The diagnoses of STEMI and myocardial infarction were established based on the actual clinical guidelines7,12. Ischemia time was defined as the time elapsed between symptom onset and reperfusion (the passage of the guide wire through the culprit artery during PCI). Target vessel revascularization and target lesion revascularization were defined following the ARC (Academic Research Consortium) criteria13.

Major adverse cardiovascular events (MACE) included all-cause mortality, acute myocardial infarction, heart failure requiring hospitalization and new, unplanned revascularizations. Following the recommendations from the ARC for the study of stent prognosis, a composite goal of major patient-oriented composite endpoint (POCE) of death from any cause, any myocardial infarctions or new unplanned revascularization was included13. The deviceoriented composite endpoint (DOCE) included cardiac death, target vessel myocardial infarction and ischemia-driven target lesion revascularization. Definite stent thrombosis was considered as angiographically proven thrombosis.

Study objectives

The main objective of this study was to compare the long-term prognosis of revascularization with DES vs BMS in consecutive patients admitted due to STEMI who underwent PCI. The clinical outcomes were assessed based on all-cause mortality, a composite of MACE, POCE, and DOCE endpoints, and on each component separately. The median follow-up was 1015 days, and the interquartile range (IQR), 400-1800 days.

Statistical analysis

The differences in the descriptive analysis were assessed using the difference of means Student t test and the chi-square test of comparison of proportions, depending on whether the variable was continuous or categorical. To minimize the bias involved when studying the prognostic effect of the DES versus the BMS implant from an observational point of view, a propensity score matching analysis was performed. The variables included in the model were age, sex, body mass index, arterial hypertension, diabetes, dyslipidemia, smoking, ischemic heart disease, time of ischemia, infarct location, culprit artery involved in the infarction, use of glycoprotein IIb/IIIa inhibitors, number of diseased vessels, the glomerular filtration rate, the creatinine levels at admission, the peak troponin I levels, hemoglobin, glucose, heart rate, systolic blood pressure, Killip class, left ventricular ejection fraction, GRACE score, CRUSADE score, and year of inclusion in the analysis. An analysis of the variance inflation factor showed no issues of multicollinearity in the variables used (variance inflation factor 1.56 and no variable > 4). The caliper used was 0.25, and the sensitivity-specificity ratio obtained was high (75% area under the curve). No variable had a strong bias, being the average bias, 3.3%. After propensity score matching, no statistically significant differences were seen in any of the variables studied.

The graphs figure 1 and figure 2 show the Nelson-Aalen estimate of the cumulative hazard function, and the differences were assessed using the log-rank test. The hazard ratio was calculated using the univariate Cox regression analaysis.

Statistical analysis was performed using the STATA 14 and SPSS 22.0 statistical packages.

Figure 1. Cumulative incidence curves for survival. BMS, baremetal stent; DES, drug-eluting stent.

Figure 2. Cumulative incidence curves for POCE and MACE-free survival. BMS, bare-metal stent; DES, drug-eluting stent; MACE, major adverse cardiovascular events; POCE, patient-oriented combined endpoint.

Results

Baseline characteristics

The overall study cohort included 1357 patients; 983 patients received BMS and 374 received DES. The patients in the DES group were younger, more frequently males, with a higher body mass index and CRUSADE scores of higher hemorrhagic risk. The patients revascularized with BMS usually had anterior wall infarctions, lower hemoglobin levels, and poor renal function. The total length of the implanted stents was higher in the DES group, and the diameter of the stents was larger in patients with BMS. There were no significant differences in other cardiovascular risk factors, time of ischemia, peak troponin levels, hemodynamic status, Killip class at admission, left ventricular ejection fraction, GRACE score, number of lesions treated, number of stents used, or pharmacological treatment at discharge, with the exception of antiplatelet therapy (table 1).

The propensity score-matched cohort study consisted of 262 patients of each pair and showed no significant differences in any of the aforementioned variables (table 1).

Table 1. Baseline characteristics of the overall cohort and the propensity score matched cohort

Events at follow-up

The events at follow-up are shown on table 2. The overall mortality rate was 16.9% (n = 205). In the overall study cohort, the DES implant was closely associated with lower risk of death from any cause (6.9% vs 12.2%; log-rank test, P < .001); the combined MACE and POCE were also less common in patients treated with DES. No differences were seen in the DOCE, cardiovascular mortality, myocardial infarction, target vessel myocardial infarction, target vessel revascularization, target lesion revascularization or revascularization by another vessel. No differences were seen in definite stent thrombosis at follow-up either.

Table 2. Adverse events during follow-up

In the propensity score-matched cohort study, patients who received a DES had a significantly lower all-cause mortality rate (6.7% vs 18.3%; log-rank test, P < .001) and lower incidence rates of MACE and POCE at follow-up (16.8% vs 25.6%, log-rank test, P = .049; 12.6% vs 22.5%, log-rank test, P = .017, respectively). Target vessel revascularization (4.6% vs 8.4%) and target lesion revascularization (4.6% vs 7.6%) tended to drop but were not statistically significant. The DOCE was numerically lower in the DES group. No differences were seen in cardiovascular mortality, myocardial infarction, target myocardial infarction or revascularization by another vessel. Survival curves revealed that both groups diverged over time compared to the beginning of the follow-up, and the differences were significant after five years of follow-up(figure 1). The cumulative incidence curves for MACE and POCE (figure 2) show a similar pattern, although the differences were statistically significant after six years of follow-up in both of them. Finally, no significant differences were observed in the rate of definite stent thrombosis showing both groups low rates of 2.7% in the BMS group and 1.9% in the DES group (log-rank test, P = .686).

Discussion

The results of this study show that in a real-world population of consecutive patients with STEMI who underwent PCI, the use of new-generation DES was associated with a lower overall mortality rate and long-term MACE and POCE and no differences in the incidence rate of definite stent thrombosis. The protective effect of DES was maintained in analyses of the cohort grouped by propensity score matching, where both subgroups had similar distributions of covariates.

Our results indicate that the use of new-generation DES in PCI in patients with STEMI is associated with a prognostic benefit compared with BMS, indicative that they may be the first-choice approach in these patients, which is consistent with the actual recommendations of the clinical practice guidelines11.

In our study, we saw a reduction in all-cause mortality in the group of revascularized patients with DES, with no differences in cardiovascular mortality. When it comes to reducing the overall mortality rate the protective effect of DES cannot be established directly; however, these findings are consistent with the long-term results of former studies10. It is known that the luminal loss of BMS is greater than that of DES14. An explanation for this difference in the overall mortality rate may have to do with a higher rate of subclinical restenosis in patients with BMS that could be causing silent ischemia, a reduced ejection fraction and/or a lower coronary flow reserve, which in the event of intercurrent events such as infections, bleeding or cancer, among others, could lead to worse prognosis. The NORSTENT study15, a large multicenter trial of 9013 patients randomized to receive new-generation DES or BMS, showed no differences in the composite primary endpoint of allcause mortality or new nonfatal myocardial infarction after 6 years of follow-up. In this study, no differences were found in the overall mortality rate. The population had a lower risk profile compared to our registry: less than one-third of the patients were admitted due to STEMI, and patients with prior percutaneous revascularization, life expectancy below 5 years, on anticoagulant therapy and with bifurcation lesions were excluded. Despite the fact that no differences were found in the primary endpoint, the DES proved their effectiveness which was associated with a reduced need for new revascularizations (16.5% vs 19.8%; P < .001) and target lesion revascularizations (5.6% vs 10.2%; P < .001). Likely due to the small sample size of our study, we saw a statistically nonsignificant tendency towards less target lesion revascularizations and target vessel revascularizations in patients who received DES.

The reduction of POCE in our registry had a similar pattern to the one observed in the 5-year follow-up of the EXAMINATION trial10, where the differences favorable to the DES grew progressively bigger during follow-up, being statistically significant from the third year onwards. In the EXAMINATION trial, DES also lowered the follow-up DOCE, being the differences statistically significant after the 3-year follow-up10. In our registry the rate of DOCE was similar to that of the EXAMINATION trial at 2 years (≈ 9%); in any case, we only found a numerical reduction of the DOCE, probably due to the lack of statistical power.

The long-term evidence available of DES vs BMS is very limited; most clinical trials that compare BMS to first-generation DES conducted <2 year-follow-up studies16-22 yet usually they showed a greater efficacy of DES at the cost of less new revascularizations of the target lesion, with no differences in other clinical events or survival. Only 2 clinical trials, the EXAMINATION18 and the COMFORTABLE-AMI, have compared second-generation DESs vs BMS in patients with STEMI, and in both cases a 1-year follow-up was conducted: in the COMFORTABLE-AMI trial, the use of biolimus-eluting stents (BioMatrix; Biosensors Europe SA, Morges, Switzerland) was associated with less new infarctions based on the culprit vessel and ischemia-guided target vessel revascularizations.23. Similarly, in the EXAMINATION study, the use of an everolimus-eluting stent (Xience V; Abbott Vascular, Santa Clara, CA, United States) was associated with lower target vessel revascularizations and target lesion revascularization rates.18. In a combined analysis of both studies, the use of DES reduced the POCE which, in turn, led to less target lesion revascularization and a lower risk of infarct-related artery new infarctions.8. The late catch-up phenomenon (ie, thrombosis or restenosis 1 year after stent implantation) has been described for first-generation DES, which has raised concerns about their long-term efficacy and safety24,25. Compared to BMS, that show maximum intimal hyperplasia at 6 months26, first-generation DES show progressive luminal loss after 2 years of angiographic follow-up27. Some studies suggest that this effect is also present in new-generation DES28. Our results and those from the long-term EXAMINATION study support the hypothesis that the clinical effectiveness of newgeneration DES in terms of increased survival and decreased MACE and POCE is seen during long-term follow-up studies.

Finally, the safety of new-generation DES when it comes to their low rate of definite stent thrombosis, with no differences from BMS being reported, is consistent with what some clinical trials have published on new DES in patients with STEMI8,10,15. On the timing of stent thrombosis, it is remarkable that there was no very late stent thrombosis among patients who received DES.

Limitations

This was a retrospective observational and nonrandomized study with consecutive inclusion of patients conducted in a single center. Thus, it is the limitations inherent to this type of study that need to be taken into consideration.

To avoid bias and to control the effects of possible confounding factors, propensity score adjustment was conducted; however, the effects of the confounding factors that were not analyzed cannot be precluded. Due to the lack of data on treatment modifications during follow-up, we cannot rule out the possibility that the observed differences may be influenced, at least partially, by treatment. Finally, the existence of the effect of heterogeneity among the different types of DES cannot be precluded either.

Conclusions

According to our registry, in a real-world population of patients, the implementation of new-generation DES compared to BMS was associated with increased survival rates at long-term follow-up, reductions of MACE and POCE and no differences in definite stent thrombosis.

Funding

This research has been funded by The MAPFRE Foundation.

Conflicts of interests

The authors declared no conflicts of interest whatsoever.

References