Characteristics of recurrent in-stent restenosis after second- and third-generation drug-eluting stent implantation.

BACKGROUND: In second- and third-generation drug-eluting stent (DES) era, in-stent restenosis (ISR) is not commonly seen. However, a few patients still need repeat revascularizations for recurrent ISR even after second- and third-generation DES implantation. METHODS: From January 2012 to March 2017, 2339 lesions underwent second- and third-generation DES (Nobori, Promus Element, Resolute Integrity, Xience, Ultimaster and Synergy) implantation, of which 95 lesions (4.1%) underwent revascularization for first ISR. All lesions were divided into two groups of recurrent ISR group and non-recurrent ISR group. After successful optical coherence tomography (OCT) guided revascularization for all lesions, we investigated characteristics of recurrent ISR, and 2 years follow-up were completed. RESULTS: The mean age was 70.8 ± 11.7 years, and 73.2% were males. Among 56 DES-ISR lesions which were assessed by OCT, recurrent ISR was seen in 33.9% (N = 19) at 2 years follow-up after revascularization for first ISR. Serum low-density lipoprotein-cholesterol (LDL-C) level was higher in recurrent ISR group compared with non-recurrent ISR group (114.1 ± 53.9 mg/dl vs. 90.9 ± 27.8 mg/dl, P = 0.04) and heterogeneous tissue pattern was more frequently found in recurrent ISR group compared with non-recurrent ISR group (63.2% vs. 27.0%, P = 0.03). Multivariate analysis identified a heterogeneous tissue pattern (odds ratio 3.71; 95% confidence interval 1.09-12.59; P = 0.03) as an independent predictor of recurrent restenosis. CONCLUSION: Recurrent ISR of second- and third-generation DES was associated with heterogeneous tissue pattern of first ISR, and high LDL-C level was associated with recurrence.

In-stent restenosis assessed with frequency domain optical coherence tomography shows smooth coronary arterial healing process in second-generation drug-eluting stents.

INTRODUCTION: The pathophysiology and mechanism of in-stent restenosis (ISR) after implantation of second-generation drug-eluting stents (DESs) are not fully clear. We compared the morphological characteristics of ISR between first- and second-generation DESs using frequency domain optical coherence tomography (OCT). METHODS: Patients who underwent follow-up coronary angiography (CAG) after first-generation (CYPHER™ and TAXUS™) and second-generation (Nobori®, PROMUS Element™, Resolute Integrity and XIENCE) DES implantations were examined. ISR was defined as lesions of over 50% diameter stenosis at follow-up CAG. Frequency domain OCT was performed at the time of revascularisation of ISR. Tissue morphology was assessed at minimum lumen area. OCT images of DESs at both early (≤ 1 year) and late (> 1 year) phase follow-up were compared. RESULTS: On qualitative OCT assessment, the ratios of homogeneous, layered, heterogeneous without-attenuation and heterogeneous with-attenuation morphologies were 57.1%, 17.1%, 20.0% and 5.7%, respectively, for second-generation DES ISR (n = 35), and 16.7%, 25.0%, 25.0% and 33.3%, respectively, for first-generation DES ISR (n = 36). At late phase follow-up, homogeneous morphology was significantly more common for second-generation DES ISR compared to first-generation DES ISR (first-generation: 8.0% vs. second-generation: 50.0%; p < 0.01) while heterogeneous with-attenuation morphology was significantly more common for first-generation DES ISR (first-generation: 44.0% vs. second-generation: 5.6%; p < 0.01). CONCLUSION: Homogeneous tissue morphology was more frequently found for second-generation than first-generation DES ISR, especially in the late phase. This suggested that neointimal hyperplasia was the main mechanism in second-generation DES ISR, and that the neointima was stabilised, much like in bare metal stent implantation.

Association of morphologic characteristics on optical coherence tomography and angiographic progression patterns of late restenosis after drug-eluting stent implantation.

OBJECTIVES: To gain insight into the pathophysiology of late drug-eluting stent (DES) restenosis. BACKGROUND: Restenosis of DES has a different time course from that of bare metal stents. METHODS: Patients who underwent follow-up coronary angiography (CAG) twice (six to nine months and 18 to 24 months) after DES implantation were examined using optical coherence tomography (OCT). All lesions with target lesion revascularization at first follow-up were excluded. Late catch-up was defined as lesions that progressed from less than 50% diameter stenosis (DS) at the first CAG to more than 50% DS at the second CAG. Lesions with the late catch-up were further divided into two groups; lesions with jump-up (less than 25% DS at the first CAG) and lesions with gradual progression (25-50% DS at the first CAG). RESULTS: Of the 25 patients who had late ISR, 23 patients (10 jump-up/13 gradual progression) were examined with OCT at late follow-up and enrolled in this study. In the qualitative OCT assessment, each ratio of homogeneous, layered, heterogeneous with or without attenuation tissue morphologies were in jump-up group, and gradual progression group were 0% and 15%, 0% and 23%, and 60% and 8%, and 40% and 54%, respectively. All of jump-up group showed heterogeneous restenotic tissue, while 62% of gradual progression group showed heterogeneous restenotic tissue (P = .04). CONCLUSIONS: These findings suggest different pathophysiology of the late catch-up after DES implantation between the jump-up and gradual progression groups.

Simple balloon dilation for drug-eluting in-stent restenosis: an optical coherent tomography analysis.

BACKGROUND: Although drug-eluting stent (DES) has significantly reduced restenosis, the treatment of DES-in-stent restenosis (ISR) remains a challenge with high restenosis rate. METHODS: We examined whether morphologic appearance of restenosis tissue by optical coherent tomography (OCT) had an impact on outcomes after balloon angioplasty for DES-ISR. The morphologic appearance of restenosis tissue was qualitatively assessed for tissue structures such as homogeneous, layered, and heterogeneous patterns. RESULTS: Using OCT, 50 patients with DES-ISR were divided into 2 groups: 25 lesions with homogeneous or layered patterns (homo/layered group) and 25 lesions with heterogeneous patterns (hetero group). Acute gain was larger in the hetero group (1.33 ± 0.41 mm vs. 1.06 ± 0.32 mm in the homo/layered group, P = 0.03). On intravascular ultrasound analysis, post-procedural percent neointimal area was smaller in the hetero group (27.4 ± 9.2% vs. 34.0 ± 11.2% in the homo/layered group, P = 0.05). Angiographic follow-up was performed in 37 lesions (74%). Follow-up minimal lumen diameter was larger in the hetero group (1.75 ± 0.89 mm vs. 1.01 ± 0.81 mm in the homo/layered group, P = 0.04). Target lesion revascularization rates tended to be lower in the hetero group (20% vs. 43% in the homo/layered group, P = 0.12). CONCLUSIONS: Balloon angioplasty was more effective for DES-ISR with heterogeneous tissue appearance than DES-ISR with homogeneous/layered tissue appearance. OCT assessment of DES-ISR morphology may be a useful adjunct in determining clinical strategies. Simple balloon dilatation is a possible treatment strategy for DES-ISR lesions with a heterogeneous appearance on OCT images.

Late regression of Cypher in-stent restenosis.

We encountered a case of late regression after sirolimus-eluting stent restenosis. We report this case with intravascular ultrasound imaging demonstrating an intraluminal echolucent tissue, which looks like a black hole.

Regulation of K(ATP) channels by P(2Y) purinoceptors coupled to PIP(2) metabolism in guinea pig ventricular cells.

We used patch-clamp techniques to elucidate the regulatory mechanisms of ATP-sensitive K(+) (K(ATP)) channels by stimulation of P(2) purinoceptors in guinea pig ventricular myocytes. Extracellular ATP at 0.1 mM transiently inhibited by 90.5 +/- 5.0% the whole cell K(ATP) channel current evoked by a reduction in intracellular ATP concentration to 0.5 mM and exposure to 30 microM pinacidil. ADP and AMP (both 1 mM) also decreased the current by 42.8 +/- 9.3% and 9.4 +/- 4.8%, respectively, but adenosine did not, even at 10 mM. ATP-induced channel inhibition was hardly observed in the presence of 0.2 mM suramin, 0.2 mM guanosine 5'-O-(2-thiodiphosphate), or 0.1 mM compound 48/80, whereas it was not influenced by the presence of 0.1 microM staurosporine or 10 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid in the pipette. In the presence of 10 microM wortmannin or the absence of ATP in the cytosol, the ATP-induced channel inhibition was irreversible. Phosphatidylinositol 4,5-bisphosphate (PIP(2)) at 0.1 mM in the outside-out patch pipette prevented ATP-induced channel inhibition. The half-maximal internal ATP concentrations for inhibition of channel activity determined in inside-out membrane patches were 13.8 microM in the presence and 1.12 mM in the absence of 0.1 mM ATP at the external side. It is concluded that activity of K(ATP) channels is modulated by extracellular ATP by a mechanism involving P(2Y) purinoceptors coupled to GTP-binding proteins associated with reduction of the sarcolemmal PIP(2) concentration via stimulation of phospholipase C.