Introduction
Plain-old balloon angioplasty (POBA) was introduced in the 1980 s, but is of limited use today due to high restenosis rates (30–50 %) and possible complications of acute and subacute vessel closure [
1]. Thus, bare metal stents (BMS) were developed to overcome these limitations at the expense of in-stent restenosis due to intimal hyperplasia. Newer generation drug-eluting stents (DES) proved to effectively suppress neointimal proliferation and delayed restenosis rates are now only 5–15 % [
2]. However, a foreign body and local hypersensitivity reactions seem to play a pivotal role for the development of restenosis and late stent thrombosis after stenting [
3,
4]. Also, positive vessel remodeling is hindered by a persistent metallic cage and preserving vasomotion after angioplasty is of growing interest.
So far, DCB angioplasty has proven its value in the interventional treatment of de novo stenosis in small coronary vessels, in-stent restenosis or for angioplasty of the side branch in bifurcation stenosis [
5‐
14]. However, there is still limited data and reluctance to treat stenoses in native coronaries of any size with this interventional strategy due to the fear of periprocedural and subacute complications with unfavorable outcome and potential need for bail-out stenting. DCB angioplasty requires only 4 weeks of dual antiplatelet therapy (DAPT), which is a considerable advantage since bleeding complications after PCI have a negative impact on clinical outcomes, and are of health-economical interest.
Discussion
The main findings of this prospective study are: (1) DCB-only angioplasty in all-comers is effective and safe with no subacute vessel closure and low MACE rate (4.7 % at 6-months) with only 4 weeks of DAPT, (2) a trend toward positive vessel remodeling with late lumen enlargement is seen at 6-month invasive f/u, (3) conversion rate to bail-out stenting under FFR guidance is very low (6 %), (4) clinically silent type A and B dissections are mostly healed at f/u, (5) angiography is unreliable for a correct diagnosis of small residual dissections.
Evidence for DCB-only angioplasty as a primary interventional strategy is growing. So far, published data are stemming from mainly retrospective registries and case reports [
14,
19‐
22]. One serial, prospective study using IVUS and FFR analyzed only 27 from 48 initially treated patients [
23]. To the best of our knowledge, this is the first prospective, officially registered study with a dedicated, predefined procedural protocol that investigates the feasibility of elective DCB-only PCI in all-comers and provides a nearly completed 6-month invasive and clinical f/u in all patients. Earlier studies of DCB-only angioplasty of de novo stenoses showed a high conversion rate to stenting (11.9–32.8 %), or investigated a preselected study population [
20,
21,
23]. Contrary, bail-out stenting in our study was necessary only in 6 % of cases.
DCB angioplasty leads to lumen enlargement at 6-month invasive f/u in many patients expressed as overall LLL of −0.13 ± 0.44 mm (Online Resource: Figs. 3a–c). Our results on positive vessel remodeling are in agreement with previous studies also showing luminal gain at variable f/u times (Scheller 2013: LLL −0.25 to −0.18 mm; Kleber 2015: late lumen increase in 69 % of the lesion, Her 2016: LLL: −0.12 ± 0.30 mm; Shin 2015: LLL 0.05 ± 0.27 mm; Ann 2016: LLL 0.02 ± 0.27 mm) [
14,
19,
21‐
23]. Only the Valentine´s II trial showed a LLL of 0.38 ± 0.39 mm at 6–9 months f/u. However, this might underline the necessity of adequate lesion preparation since predilation in the Valentine´s II trial was conducted in only 85 %, and DCB diameters were significantly smaller despite comparable RLDs. Contrary to the consensus on DCB treatment, the mean
b/
a ratio of 1.27 in this study was considerably higher than recommended (0.8–1.0), but is in line with values reported by other studies (1.15–1.18). Thus, oversizing seems of crucial importance to achieve sufficient acute and long-term results [
14,
21,
22].
Post-interventional FFR is less well evaluated, but pressure gradient measurements proved to be a useful and reliable tool to guide immediate results of angioplasty [
24,
25]. In our study, we used a cut-off of >0.8 for post-interventional FFR, which one might find unusually low to accept final angioplasty results. FFR values <0.95 post-stenting are associated with adverse long-term results [
24]. However, to the best of our knowledge, cut-off values for FFR after a DCB-only procedure have never been investigated yet. Also, given the higher acute lumen gain after stent implantation, and the expected late lumen enlargement after DCB-only angioplasty, one must not extrapolate data from publications investigating stent results. In this light, clinical and angiographic data in our study seem reassuring for FFR values > 0.8 after DCB-only, but this hypothesis needs confirmation in further studies with longer follow-up times.
Polymers in DES platforms are associated with disadvantageous vessel wall effects, while DCB are polymer-free. DCB angioplasty allows uniform distribution of the antiproliferative drug to the vessel wall, and significantly higher paclitaxel-concentrations are used compared to paclitaxel-eluting stents [
26,
27]. However, properties of DCB´s should not be understood as “class effects” [
28]. Current evidence for vessel wall expansion is the strongest for paclitaxel and is histologically proven as media wall thinning and cell necrosis in addition to inhibition of smooth muscle cells [
18,
29‐
31]. Out of the available paclitaxel-coated balloons, the Sequent Please™ DCB used in this study has been best investigated. This is of importance since vessel wall effects of paclitaxel are known to be dose-dependent [
32,
33].
We found no aneurysm formation at the stenotic site at f/u, which confirms another study that specifically investigated the incidence of focal coronary artery aneurysm after DCB angioplasty [
34].
Plaque regression might also account for the specific effects of positive vessel remodeling. A small, serial IVUS study found no change of mean plaque area 9 months after DCB angioplasty but a significant decrease of atheroma volume [
23]. The mentioned study also found plaque modulation since out of nine initially observed TCFA’s only five TCFA’s were seen at f/u, which the authors interpreted as a result of cap thickening and transformation to pathological intimal thickening [
23]. In line with this observation, we did not find any TCFA’s at 6-month f/u within the treated segment using OCT, which is more reliable in determining TCFAs than IVUS [
35].
Another focus of our study was the evaluation of dissections as a result of angioplasty and its impact on midterm outcomes. By applying the mentioned procedural precautions and intracoronary pressure monitoring, bail-out stenting was grossly preventable. From the only small residual dissections seen at baseline, most dissections were completely healed at f/u, which is in line with a previously published study [
36]. Interestingly, angiography is largely misleading in evaluation of small dissections of NHLBI type A, and no real association between dimensions of dissection investigated by OCT and angiography was found.
Novel interventional approaches for the therapy of stable stenosis try to eliminate the necessity for a permanent foreign body since it has been shown that in-stent restenosis is at least partly caused by local hypersensitivity reactions and neoatherosclerosis in response to the metal material, the polymer or the antiproliferative drug [
37]. Lately, bioresorbable vascular scaffolds (BVS) are in the focus of interest. Interestingly, for both “metallic free” concepts of BVS and DCB-only angioplasty, late lumen enlargement has been shown, which is contrary to the well-known vessel response after POBA, BMS or DES implantation resulting always in late lumen loss [
38,
39]. Also, restoration of vasomotion after angioplasty is advantageous and might maintain positive long-term outcomes including relief of angina symptoms [
39,
40]. However, prolonged DAPT for 12 months is needed after BVS implantation. Also, rates of acute and late scaffold thrombosis are not negligible, and seem to be higher compared to newer generation DES [
41]. Degradation of the ABSORB™ BVS, which is currently the best investigated scaffold, is with >2 years rather slow and the optimal degradation rate of vascular scaffolds remains to be determined [
39]. Contrarily, duration of DAPT after DCB-only angioplasty is with 4 weeks only minimal and reports on acute vessel closure after PCI are very rare. Thus, DCB angioplasty as a stand-alone procedure might be a promising trade-off between POBA, DES, and BVS. On the other hand, it has been shown that BVS has the capacity to “seal” underlying coronary plaques [
39,
42]. Whether or not this translates into a favorable long-term course remains nevertheless unclear. Changes in coronary plaques after a DCB-only procedure need to be further investigated, before definitive conclusions and clinical recommendations comparing both concepts can be formulated.
Clinical implications
FFR-guided DCB-only PCI using the Sequent Please balloon is feasible, safe, and effective irrespective of vessel size. Small, non-flow-limiting dissections type A and B with normal FFR values >0.80 do not require stenting and show favorable clinical outcomes. Operator’s training including lesion preparation, choice of balloon size, inflation time and pressure, and evaluation of dissections is necessary to successfully apply a DCB-only strategy as stand-alone procedure and to achieve good clinical outcomes.
Limitations
This study has a relatively small sample size and was intended as a feasibility study to prove the concept of an elective FFR-guided DCB-only angioplasty. Thus, our study is not a randomized trial comparing DCB-only PCI to another study intervention. Since we did not perform OCT at baseline, plaque regression and dissection healing could not be recorded and further serial OCT studies specifically focusing on this aspect are needed.