Original Contribution

Clinical and Angiographic Outcomes After Drug-Eluting Stent Implantation With Triple-Kissing-Balloon Technique for Left Main Trifurcation Lesion: Comparison of Single-Stent and Multi-Stent Procedures

Shunsuke Kubo, MD;  Kazushige Kadota, MD, PhD;  Mahmoud Sabbah, MD;  Suguru Otsuru, MD; Daiji Hasegawa, MD;  Seiji Habara, MD;  Takeshi Tada, MD, PhD;  Hiroyuki Tanaka, MD;  Yasushi Fuku, MD; Harumi Katoh, MD, PhD;  Tsuyoshi Goto, MD;  Kazuaki Mitsudo, MD

Shunsuke Kubo, MD;  Kazushige Kadota, MD, PhD;  Mahmoud Sabbah, MD;  Suguru Otsuru, MD; Daiji Hasegawa, MD;  Seiji Habara, MD;  Takeshi Tada, MD, PhD;  Hiroyuki Tanaka, MD;  Yasushi Fuku, MD; Harumi Katoh, MD, PhD;  Tsuyoshi Goto, MD;  Kazuaki Mitsudo, MD

Abstract: Objectives. This study evaluated clinical and angiographic outcomes after drug-eluting stent (DES) implantation with triple-kissing-balloon technique (triple-KBT) for left main (LM) trifurcation lesions and compared them between single-stent and multi-stent procedures. Background. The triple-KBT is a challenging strategy to treat LM trifurcation lesions with both single-stent and multi-stent procedures, and its outcomes after DES implantation were unknown. Methods. We evaluated 72 patients who underwent triple-KBT after DES implantation for LM trifurcation lesions from April 2005 to October 2012, and compared the clinical and angiographic outcomes between 45 patients in the single-stent group and 27 patients in the multi-stent group. Patients with 2 or 3 stents implanted were included in the multi-stent group. Results. Procedural success was obtained in 93.1% of all patients, with no in-hospital death, myocardial infarction, and target lesion revascularization (TLR). The median follow-up duration was 838 days. The incidence of all-cause death at 3 years was 8.6%, and there was no significant difference between the single-stent and multi-stent groups (8.0% vs 9.7%; P=.82). There were no patients with myocardial infarction or stent thrombosis. The incidence of TLR at 3 years was 14.5%, and it was significantly higher in the multi-stent group (31.3%) than in the single-stent group (4.6%; P=.01). No incidence of TLR was observed beyond 1 year in both groups. Conclusion. DES implantation with triple-KBT was a safe and feasible technique for LM trifurcation lesion. The favorable clinical outcomes could be achieved by single-stent procedure compared with multi-stent procedure. 

J INVASIVE CARDIOL 2014;26(11):571-578

Key words: percutaneous coronary intervention, drug-eluting stent, left main trifurcation lesion, kissing-balloon technique

________________________________________

Percutaneous coronary intervention (PCI) for left main (LM) bifurcation lesions has been performed more frequently as indications for drug-eluting stent (DES) have expanded.1,2 However, LM trifurcation lesions remain a challenging field for interventional cardiologists due to the complexity of the lesion and PCI procedure. PCI for LM trifurcation lesions is infrequent, and the optimal technique remains unclear. After PCI for LM bifurcation lesions, short-term and long-term outcomes, particularly with double-stent procedures, tend to be less favorable when compared to those after PCI for LM ostium or shaft lesions.3-5 When bifurcation stenting is performed, kissing-balloon technique (KBT) plays an important role in optimization of stent apposition, improvement of side-branch (SB) access, and prevention of SB occlusion.6-9 In several case reports of PCI for LM trifurcation lesions, triple-KBT was reported to be necessary to obtain optimal clinical and angiographic results.10-12 Although triple-KBT could be a promising technique, there are no data available to support triple-KBT after DES implantation for LM trifurcation lesions. Furthermore, the impact of stenting strategy on the clinical and angiographic outcomes after DES implantation with triple-KBT for LM trifurcation lesions is unknown.

In this study, we investigated the clinical and angiographic outcomes of triple-KBT after DES implantation for LM trifurcation lesions and compared them between single-stent and multi-stent procedures.

Methods

Study population. From April 2005 to October 2012, a total of 1113 consecutive patients underwent DES implantation of the distal LM coronary artery with KBT at Kurashiki Central Hospital. Among these patients, we enrolled 72 consecutive patients who had undergone triple-KBT after DES implantation for distal LM trifurcation lesions, including both protected and unprotected LM coronary artery lesions. Forty-five patients were treated with the single-stent procedure (single-stent group), and 27 with the multi-stent procedure including double-stent and triple-stent implantation (multi-stent group). All patients provided informed consent for the procedure and subsequent data collection.

The main branch (MB) was defined as the biggest branch with the largest perfusion. The branch with the narrowest angle from the distal MB was defined as SB1, and the other as SB2. The side branch size was ≥2.25 mm at baseline angiography or after predilatation. Distal LM trifurcation lesions were classified by angiographic assessment according to the modified Medina classification (Figure 1).12,13 

Treatment strategy. PCI was performed with a 7 or 8 Fr guiding catheter. Predilatation of the SB was dependent on the operator’s discretion. Stenting was performed across the trifurcation, and proximal optimization technique (POT) with a non-compliant balloon was recommended after stenting. The double-stent procedure, consisting of V-stenting, T-stenting, and culotte stenting, was considered in patients with significant stenosis or residual dissection of SBs. Rewiring to the SB1 and SB2 was performed using a double-lumen multifunctional probing microcatheter (Crusade; Kaneka Corporation) with an effective structure for bifurcation lesions. The wire protruding from the end of the monorail lumen can stabilize the microcatheter, and the other wire protruding from the side hole in the over-the-wire lumen can be directed toward the ostium of the intended branch.14 The recommended steps for rewiring to the SB and the subsequent triple-KBT in this study are shown in Figure 2. During kissing-balloon dilatation, inflation by non-compliant balloon was strongly recommended at the MB. Intravascular ultrasound (IVUS) and debulking devices were used at the operator’s discretion. PCI for LM trifurcation lesions was performed by six experienced operators in this study. Figures 3A and 3B represent two cases treated with triple-KBT after single-stent or double-stent procedures and POT. Procedural success was defined as a composite of the following: residual diameter stenosis <30% of stented branches, thrombolysis in myocardial infarction (TIMI) flow grade 3 in all branches, and in-hospital death/myocardial infarction (MI)/target lesion revascularization (TLR)/stroke-free outcomes. Before the procedure, patients were given loading doses of aspirin (200 mg) and ticlopidine (400 mg) or clopidogrel (300 mg) unless they had previously received antiplatelet therapy. After the procedure, patients were maintained on aspirin (100 mg once daily) for life and ticlopidine (200 mg twice daily) or clopidogrel (75 mg once daily) for at least 12 months.

Clinical follow-up. We collected clinical data on all-cause death, cardiac death, non-fatal MI, stent thrombosis, TLR, and target trifurcation revascularization (TTR). Clinical information was obtained either from a review of the hospital records or by telephone interviews with the patients, family members, or primary care physicians. Stent thrombosis was defined on the basis of the Academic Research Consortium definitions.15 MI was defined as ischemic symptoms and/or ischemic changes on an electrocardiogram plus elevation of creatine kinase levels to twice the upper limit of normal, together with a rise in creatine kinase-MB fraction. TLR was defined as either repeat PCI or coronary artery bypass grafting due to restenosis or thrombosis of the target lesion within 5 mm of the proximal and distal edge segments and the ostium of each SB. TTR was defined as either repeat PCI or coronary artery bypass grafting due to restenosis within 5 mm proximal or distal of the carina of trifurcation.12

Angiographic follow-up. According to the institutional protocol, follow-up coronary angiography was scheduled at 3, 8, and 20 months after the index PCI. Among these angiographic data, patients who had undergone follow-up angiography at 8 months after PCI were included in the angiographic analysis. Furthermore, patients who had undergone unscheduled follow-up angiography within 1 year for clinical reasons were also included in the angiographic analysis. Quantitative coronary angiographic analysis was performed using QCA-CMS (Medis Medical Imaging Systems). All angiograms were analyzed in a random sequence by two experienced observers who were blinded to the clinical characteristics of the patients. Angiographic measurements were obtained in multiple views following intracoronary nitrate injections. Reference diameter, minimum luminal diameter (MLD), and diameter stenosis were measured before and after intervention. In-stent restenosis was defined as percent diameter stenosis (%DS) of >50% by quantitative coronary analysis. SYNTAX scores, based on diagnostic angiograms obtained before PCI, were retrospectively calculated by two experienced interventional cardiologists blinded to the clinical data (SYNTAX score calculator available online at http://www.syntaxscore.com). In patients who had undergone coronary artery bypass grafting, the SYNTAX score was calculated presuming occlusion of bypass grafts.

Statistical analysis. Data were expressed as mean ± standard deviation (SD) for continuous variables. Values were reported as numbers with relative percentages or standard deviations. Continuous values were compared using unpaired Student’s t-test or Mann-Whitney U-test on the basis of distribution. Categorical variables were compared using a chi-square test or Fisher’s exact test. A P-value of <.05 was considered statistically significant. The cumulative incidence of clinical events was estimated by the Kaplan-Meier method, and differences were assessed using the log-rank test. IBM SPSS statistical software (version 20, IBM Corporation) was used for all statistical calculations.

Results

Baseline patient characteristics are shown in Table 1. The mean age was 67.7 ± 12.1 years, and the mean left ventricular ejection fraction was 55.5 ± 11.8%, with no significant difference between the 2 groups. The prevalence of acute coronary syndrome at clinical presentation was significantly higher in the multi-stent group (25.9%) than in the single-stent group (4.3%; P=.01). There were 4 patients (5.6%) with protected LM trifurcation lesion and 68 patients (94.4%) with unprotected LM trifurcation lesion. Table 2 shows the lesion and procedural characteristics. A 7 Fr guiding catheter was used in 62 patients (86.1%). The stenting techniques used in the double-stent group were culotte stenting in 22 patients, provisional T-stenting in 9 patients, V-stenting in 2 patients, and modified T-stenting in 1 patient. In the multi-stent group, 7 patients underwent triple-stent implantation with a combination of culotte and provisional T-stentings. Rewiring to the SB was performed using a double-lumen multifunctional probing microcatheter in all patients. The prevalence of a true trifurcation lesion was 44.4% of all patients, and it was significantly higher in the multi-stent group (74.1%) than in the single-stent group (26.7%; P<.001). The mean SYNTAX score of all patients was 32.4 ± 11.5, and there was no significant difference between the single-stent and multi-stent groups (30.6 ± 12.0 vs 35.4 ± 10.2, respectively; P=.09). IVUS-guided PCI was performed in 77.8% of all patients (80.0% in the single-stent group vs 74.1% in the multi-stent group; P=.45). POT was performed in 46.7% of the single-stent group and in 33.3% of the multi-stent group (P=.33). There was no significant difference between the two groups in terms of mean stent size and mean stent length of the MB. The balloon sizes of the MB and SB1 during triple-KBT were similar between the 2 groups, whereas the balloon size of the SB2 was larger in the multi-stent group (2.92 ± 0.51 mm) than in the single-stent group (2.59 ± 0.43 mm; P<.01).

Procedural success was obtained in 67 patients (93.1%), and there was no incidence of in-hospital death, MI, stent thrombosis, or TLR in any patient. In 5 patients (4 in the single-stent group and 1 in the multi-stent group) with no procedural success, postprocedural diameter stenosis of the MB was >30%, but not a significant stenosis. After the procedure, significant residual stenosis of the SB1 remained in 2 patients, but occlusion of the SB did not occur in any patients. There were no patients who needed mechanical support during PCI. Follow-up coronary angiography was performed in 65 patients (90.2%; 41 in the single-stent group and 24 in the multi-stent group). Serial angiographic results are shown in Table 3. Angiographic data for the MB were similar between the 2 groups. The reference diameter of the SB2 was significantly larger in the multi-stent group (2.67 ± 0.46 mm vs 3.07 ± 0.44 mm; P<.01). The multi-stent group had more severe stenosis in baseline angiography of both SB1 and SB2 than the single-stent group, whereas postprocedural stenosis was better in the multi-stent group. In follow-up angiography, no significant difference was observed in the binary restenosis rate between the single-stent and multi-stent groups in the MB (9.8% vs 4.2%; P=.64), SB1 (29.3% vs 41.7%; P=.42), and SB2 (22.0% vs 25.0%; P=.77). Late lumen loss was also similar between the two groups in the MB (0.49 ± 0.72 mm vs 0.50 ± 0.73 mm; P=.70), SB1 (0.47 ± 0.46 mm vs 0.45 ± 0.48 mm; P=.42), and SB2 (0.35 ± 0.65 mm vs 0.63 ± 0.80 mm; P=.12).

The median clinical follow-up duration was 838 days (interquartile range [IQR], 519-1100 days). The cumulative incidence of all-cause death at 3 years was 8.6% in all patients, and there was no significant difference between the single-stent and multi-stent groups (8.0% vs 9.7%; P=.82) (Table 4 and Figure 4A). Two deceased patients from the multi-stent group underwent double-stent implantation during the procedure. Among 5 patients who died during the study period, cardiac death occurred in 2 patients (1 patient due to congestive heart disease and 1 patient due to sudden death during hemodialysis). There were no patients with MI or stent thrombosis during the study follow-up period. The incidence of TLR at 3 years was 14.5% in all patients and was significantly higher in the multi-stent group (31.3%) than in the single-stent group (4.6%; P=.01) (Figure 4B). Patients with target lesion coronary artery bypass grafting were not observed. Among 10 patients who underwent TLR, 4 patients with multi-stent procedure had unstable angina, 1 patient with single-stent procedure had effort angina, 1 patient with multi-stent procedure had silent ischemia detected by non-invasive tests, and 1 patient with single-stent procedure and 3 patients  with multi-stent procedure had restenosis at 8-month follow-up angiography. TLR was performed within 1 year after the initial procedure in all cases, and no case of TLR was observed beyond 1 year. Among the multi-stent group, the cumulative incidence of TLR was 43.9% (n = 3) in patients with triple-stent implantation and 27.4% (n = 5) in patients with double-stent implantation (P=.36). Furthermore, the incidence of TTR at 3 years was also significantly higher in the multi-stent group (23.8%) than in the single-stent group (2.3%; P=.01). Among 32 patients with true trifurcation lesion (12 in the single-stent group and 20 in the multi-stent group), the incidence of TLR was 8.3% (1 patient) in the single-stent group and 30.9% (6 patients) in the multi-stent group (P=.16). 

Discussion

The main findings in this study were as follows: (1) triple-KBT after DES implantation for LM trifurcation lesions is a safe and feasible technique with a high procedural success rate and favorable hard clinical outcomes; (2) the TLR rate at 3 years after DES implantation with triple-KBT for LM trifurcation lesions was significantly lower in the single-stent procedure than in the multi-stent procedure; and (3) there was no incidence of TLR beyond 1 year in both single-stent and multi-stent groups.

Clinical and angiographic outcomes after PCI for LM trifurcation lesion have been reported in some small studies.12,16-18 Triple-KBT was performed in a portion of these studies. Triple-KBT is technically more complex than double-KBT because rewiring of the SB must be performed twice after DES implantation. Previous studies showed that rewiring through the stent strut cell closest to the carina provides optimal scaffolding of the SB ostium.19,20 In this study, using a double-lumen multifunctional probing microcatheter may have made rewiring through the distal cell effective. Furthermore, the selective use of POT (41.7%) and a high rate of IVUS guidance (77.8%) were observed in this study. POT was reported to improve MB stent apposition and facilitate safe SB rewiring to a distal stent strut.21 A previous study showed IVUS-guided PCI to be associated with favorable outcomes for the LM coronary artery.22 These factors may be responsible for our results of no procedural complications and no in-hospital adverse events. In contrast, the residual diameter stenosis of SB in our study tended to be high compared with a previous study.12 This may have occurred because we avoided additional stenting for residual stenosis of SB with favorable TIMI flow after MB stenting with KBT.

The clinical outcomes during the follow-up period were favorable, with a low incidence of cardiac death and no incidence of MI or stent thrombosis. Furthermore, the TLR rate at 3 years was 14.5%, which was comparable to stenting for LM distal bifurcation lesions.4,5 Previous studies of PCI for LM trifurcation lesions reported TLR rates ranging between 19% and 32% within 2-3 years after the procedure.12,16-18 Although our study did not show a comparison between groups with and without triple-KBT for LM trifurcation lesions, it showed that triple-KBT after DES implantation was safe and effective for LM trifurcation lesions. 

Among the LM bifurcation and trifurcation lesions, the double-stent procedure was reported to be associated with a higher TLR rate than the single-stent procedure.5,23,24 In the current study, TLR rate was much lower in the single-stent group than in the multi-stent group. Of note, the incidence of TLR at 3 years was only 4.6% in the single-stent group with triple-KBT. Furthermore, even in true trifurcation lesions, the TLR rate of the single-stent procedure with triple-KBT was 8.3%. These results showed that the single-stent procedure with triple-KBT was a recommended technique for LM trifurcation lesions. However, some cases need double- or triple-stent implantation, considering the large perfusion area of SB, SB bailout, and the large plaque burden of the carina. In this study, the TLR rate at 3 years following the multi-stent procedure was 31.3%. Therefore, this strategy has the significant limitation of a high TLR rate. For LM trifurcation lesions requiring multiple stenting, further investigation of the procedural technique is necessary. Regarding the follow-up angiographic results, there were no significant differences between the single-stent and multi-stent groups. The stenosis and perfusion area of the combined MB, SB1, and SB2 have an effect on the TLR rate; therefore, the angiographic results of each branch may not necessarily reflect the incidence of TLR in this study. Late TLR after DES implantation has emerged as a clinical problem.25 However, no TLR was observed beyond 1 year after DES implantation with triple-KBT in this study, particularly in the multi-stent group. We speculate that when performing triple-KBT in cases requiring stenting of both left anterior descending artery and left circumflex artery, suboptimal dilatation of stents caused by balloon dilatation of the non-stented branch may lead to early TLR in the multi-stent group. Nonetheless, our study could be important to clarify the long-term safety and efficacy of DES implantation with triple-KBT for LM trifurcation lesions.

Study limitations. The current study had several important limitations. First, this was a retrospective, observational, and single-center study. Second, selection of treatment strategies for LM trifurcation lesions was not randomized and was dependent on the operator’s discretion; therefore, selection bias with regard to treatment strategy may have influenced the study results. Third, comparisons between patient subgroups may not have had adequate statistical power to detect significant differences due to the limited number of patients with LM trifurcation lesion. Finally, we did not compare triple-KBT to double-KBT or non-KBT for LM trifurcation lesions to claim a clinical and angiographic advantage.

Conclusion

DES implantation with triple-KBT is a safe and feasible technique for LM trifurcation lesion. When using triple-KBT for LM trifurcation lesions, favorable clinical outcomes could be achieved by single-stent procedure compared with multi-stent procedure.

References

  1. Chieffo A, Stankovic G, Bonizzoni E, et al. Early and mid-term results of drug-eluting stent implantation in unprotected left main. Circulation. 2005;111(6):791-795.
  2. Park SJ, Kim YH, Lee BK, et al. Sirolimus-eluting stent implantation for unprotected left main coronary artery stenosis: comparison with bare metal stent implantation. J Am Coll Cardiol. 2005;45(3):351-356.
  3. Chieffo A, Park SJ, Valgimigli M, et al. Favorable long-term outcome after drug-eluting stent implantation in non-bifurcation lesions that involve unprotected left main coronary artery: a multicenter registry. Circulation. 2007;116(2):158-162.
  4. Palmerini T, Sangiorgi D, Marzocchi A, et al. Ostial and midshaft lesions vs bifurcation lesions in 1111 patients with unprotected left main coronary artery stenosis treated with drug-eluting stents: results of the survey from the Italian Society of Invasive Cardiology. Eur Heart J. 2009;30(17):2087-2094.
  5. Toyofuku M, Kimura T, Morimoto T, et al. Three-year outcomes after sirolimus-eluting stent implantation for unprotected left main coronary artery disease: insights from the j-Cypher registry. Circulation. 2009;120(19):1866-1874.
  6. Ge L, Airoldi F, Iakovou I, et al. Clinical and angiographic outcome after implantation of drug-eluting stents in bifurcation lesions with the crush stent technique: importance of final kissing balloon post-dilation. J Am Coll Cardiol. 2005;46(4):613-620.
  7. Gwon HC, Hahn JY, Koo BK, et al. Final kissing ballooning and long-term clinical outcomes in coronary bifurcation lesions treated with single-stent technique: results from the COBIS registry. Heart. 2012;98(3):225-231.
  8. Sgueglia GA, Chevalier B. Kissing balloon inflation in percutaneous coronary interventions. JACC Cardiovasc Interv. 2012;5(8):803-811.
  9. Hariki H, Shinke T, Otake H, et al. Potential benefit of final kissing balloon inflation after single stenting for the treatment of bifurcation lesions--insights from optical coherence tomography observations. Circ J. 2013;77(5):1193-1201. Epub 2013 Feb 27.
  10. Lindsey RL, Jr., Saporito J, Kleist PC, et al. Triple balloon-on-a-wire or “menage a trois” coronary angioplasty. Cathet Cardiovasc Diagn. 1993;28(1):76-79.
  11. El-Jack SS, Pornratanarangsi S, Ormiston JA, et al. Stenting coronary trifurcation lesions: is “menage a trois” the solution? Catheter Cardiovasc Interv. 2006;67(3):372-376.
  12. Tamburino C, Tomasello SD, Capodanno D, et al. Long-term follow-up after drug eluting stent implantation in left main trifurcations. EuroIntervention. 2009;5(4):432-437.
  13. Medina A, Suarez de Lezo J, Pan M. [A new classification of coronary bifurcation lesions]. Rev Esp Cardiol. 2006;59(2):183.
  14. Chiu CA. Recanalization of difficult bifurcation lesions using adjunctive double-lumen microcatheter support: two case reports. J Invasive Cardiol. 2010;22(6):E99-E103.
  15. Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007;115(17):2344-2351.
  16. Sheiban I, Gerasimou A, Bollati M, et al. Early and long-term results of percutaneous coronary intervention for unprotected left main trifurcation disease. Catheter Cardiovasc Interv. 2009;73(1):25-31.
  17. Furuichi S, Sangiorgi GM, Palloshi A, et al. Drug-eluting stent implantation in coronary trifurcation lesions. J Invasive Cardiol. 2007;19(4):157-162.
  18. Shammas NW, Shammas GA, Jerin M, et al. Treatment of left main coronary trifurcation lesions with the paclitaxel drug-eluting stent: mid-term outcomes from a tertiary medical center. J Invasive Cardiol. 2009;21(7):321-325.
  19. Ormiston JA, Webster MW, El Jack S, et al. Drug-eluting stents for coronary bifurcations: bench testing of provisional side-branch strategies. Catheter Cardiovasc Interv. 2006;67(1):49-55.
  20. Di Mario C, Iakovou I, van der Giessen WJ, et al. Optical coherence tomography for guidance in bifurcation lesion treatment. EuroIntervention. 2010;6 Suppl J:J99-J106.
  21. Stankovic G, Lefevre T, Chieffo A, et al. Consensus from the 7th European Bifurcation Club meeting. EuroIntervention. 2013;9(1):36-45.
  22. Park SJ, Kim YH, Park DW, et al. Impact of intravascular ultrasound guidance on long-term mortality in stenting for unprotected left main coronary artery stenosis. Circ Cardiovasc Interv. 2009;2(3):167-177. Epub 2009 Apr 21.
  23. Palmerini T, Marzocchi A, Tamburino C, et al. Impact of bifurcation technique on 2-year clinical outcomes in 773 patients with distal unprotected left main coronary artery stenosis treated with drug-eluting stents. Circ Cardiovasc Interv. 2008;1(3):185-192.
  24. Chen SL, Ye F, Zhang JJ, et al. Prediction of clinical outcomes in patients with unprotected left main trifurcation lesions treated by drug-eluting stents: importance of double-stent technique and SYNTAX score. J Interv Cardiol. 2010;23(4):352-357.
  25. Kimura T, Morimoto T, Nakagawa Y, et al. Very late stent thrombosis and late target lesion revascularization after sirolimus-eluting stent implantation: five-year outcome of the j-Cypher Registry. Circulation. 2012;125(4):584-591.

______________________________________

From the Department of Cardiology, Kurashiki Central Hospital, Kurashiki, Japan.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted September 23, 2013, provisional acceptance given January 6, 2014, final version accepted March 8, 2014.

Address for correspondence: Shunsuke Kubo, MD, Department of Cardiology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki 710-8602, Japan. Email: daba-kuboshun101@hotmail.co.jp

/sites/invasivecardiology.com/files/wm%20571-578%20Kubo%20JIC%20Nov%202014.pdf