The Tryton® dedicated bifurcation stent: Five-year clinical outcomes.

AIMS: We report the first 5 year clinical follow-up data for the Tryton® bifurcation stent. METHODS AND RESULTS: Clinical outcomes at five years were collected from 8 centres. Non-hierarchical Major Adverse Cardiovascular Events (MACE) and Major Adverse Cerebrovascular and Cardiovascular Events (MACCE) were collected. Diabetic and non-diabetic populations were compared, along with small (≤2.5 mm) vs large (>2.5 mm) side branch size. 173 patients with a follow up rate of 98% at 5 years were analysed. Non-hierarchical MACE was low at 9.8%, consisting of cardiac death of 1.2% (n = 2) and MI of 1.7% (n = 3). Target lesion revascularization (TLR) rate was 6.9% (n = 12). Non-hierarchical MACCE was also low, with major bleeding in 2.3% (n = 4) and strokes in 1.7% (n = 3) of patients. There was only 1 case (0.6%) of stent thrombosis that was definite and occurred very late (782 days). All-cause mortality was low, with 8.7% combined cardiac and non-cardiac death (n = 15). Diabetic patients had significantly higher event rates, but there was no difference in events with lesion stratification by side branch size. CONCLUSIONS: The Tryton® Side-Branch Stent has a non-hierarchical MACE of 9.8% and MACCE of 13.9% at 5 years. The TLR was 6.9% with only 1 case of stent thrombosis recorded.

Potentially increased incidence of scaffold thrombosis in patients treated with Absorb BVS who terminated DAPT before 18 months.

AIMS: The aim of this study was to investigate the impact of dual antiplatelet therapy (DAPT) termination on late and very late scaffold thrombosis (ScT) in patients treated with the Absorb bioresorbable vascular scaffold (BVS). METHODS AND RESULTS: Data from the registries of three centres were pooled (808 patients). To investigate the effect of DAPT termination on ScT after a minimum of six months, we selected a subgroup ("DAPT study cohort" with 685 patients) with known DAPT status >6 months and excluded the use of oral anticoagulants and early ScT. In this cohort, definite/probable ScT incidence for the period on DAPT was compared to ScT incidence after DAPT termination. ScT incidence was 0.83 ScT/100 py with 95% confidence interval (CI): 0.34-1.98. After DAPT termination, the incidence was higher (1.77/100 py; 95% CI: 0.66-4.72), compared to the incidence on DAPT (0.26/100 py, 95% CI: 0.04-1.86; p=0.12) and increased within the month after DAPT termination (6.57/100 py, 95% CI: 2.12-20.38; p=0.01). No very late ScT occurred in patients who continued on DAPT for a minimum of 18 months. CONCLUSIONS: The incidence of late and very late definite/probable ScT was acceptable. The incidence was low while on DAPT but potentially higher when DAPT was terminated before 18 months.

Integrated Biomarker and Imaging Study 3 (IBIS-3) to assess the ability of rosuvastatin to decrease necrotic core in coronary arteries.

AIMS: Statins are highly effective in reducing major adverse clinical events, but the direct effects on coronary plaque composition remain debatable. Our aim was to mechanistically evaluate the treatment effect of high-intensity statin therapy on compositional coronary plaque changes. METHODS AND RESULTS: The third Integrated Biomarker and Imaging Study (IBIS-3) was a prospective, investigator-initiated, single-centre study. Serial radiofrequency intravascular ultrasound (RF-IVUS) measurements of a predefined non-stenotic segment in a non-culprit coronary artery were performed to evaluate the effect of rosuvastatin (intended dose: 40 mg daily) on necrotic core (NC) volume in patients with stable angina or acute coronary syndrome. Changes in lipid core burden index (LCBI) were evaluated through serial near-infrared spectroscopy (NIRS) imaging in a subset. Serial RF-IVUS (and NIRS) data of a median segment of 41 mm (interquartile range: 32 to 49 mm) were complete in 164 (103) patients. Follow-up measurements were performed at six and 12 months in 30 (26) and 134 (77) patients, respectively. Mean levels of low-density lipoprotein cholesterol decreased by 30%, from 2.49 mmol/l to 1.73 mmol/l at the end of follow-up. High-dose rosuvastatin therapy resulted in a non-significant change of -1.4 mm3 (95% CI: -3.0, 0.1) in NC volume during follow-up (p=0.074). The change in NC percentage of total plaque volume was -1.4% (95% CI: -2.4 to -0.4; p=0.006). A neutral effect was also observed on LCBI. Indications of significant regression of NC volume and LCBI in the highest baseline quartiles were observed, which should cautiously be regarded as hypothesis-generating. CONCLUSIONS: High-intensity rosuvastatin therapy during one year resulted in a neutral effect on NC and LCBI within non-stenotic, non-culprit coronary segments with a relatively low atheroma burden. This study has been registered in The Netherlands Trial Register (NTR) nr. 2872.

Long-term results of BVS implantation: a focus on safety and efficacy of the bioresorbable technology.

The everolimus eluting bioresorbable vascular scaffold (BVS) represents a novel technology and a novel paradigm for treatment of coronary artery disease, with the potential of improving the long-term clinical outcomes after complete bioresorption. The increasing amount of clinical data is adding in a gradual understanding of the appropriate implantation technique, but long-term results after BVS implantation are sparse. In addition, concern related to a possible increased rate of scaffold thrombosis has recently risen. The present article reviews the current status of knowledge on bioresorbable vascular scaffold from the preclinical phase and the first-in-man experience to the recently reported large randomized trials. Challenging subsets are discussed as well as possible factors impacting on the occurrence of thrombotic events, particularly focusing on clinical outcomes reported in the longest follow-ups currently available.

Predictors of subjective health status 10 years post-PCI.

BACKGROUND: Subjective health status is an increasingly important parameter to assess the effect of percutaneous coronary intervention (PCI) in clinical practice. Aim of this study was to determine medical and psychosocial predictors of poor subjective health status over a 10 years' post-PCI period. METHODS: We included a series of consecutive PCI patients (n = 573) as part of the RESEARCH registry, a Dutch single-center retrospective cohort study. RESULTS: These patients completed the 36-item Short-Form Health Survey (SF-36) at baseline and 10 years post-PCI. We found 6 predictors of poor subjective health status 10 years post-PCI: SF-36 at baseline, age, previous PCI, obesity, acute myocardial infarction as indication for PCI, and diabetes mellitus (arranged from most to least numbers of sub domains). CONCLUSIONS: SF-36 scores at baseline, age, and previous PCI were significant predictors of subjective health status 10 years post-PCI. Specifically, the SF-36 score at baseline was an important predictor. Thus assessment of subjective health status at baseline is useful as an indicator to predict long-term subjective health status. Subjective health status becomes better by optimal medical treatment, cardiac rehabilitation and psychosocial support. This is the first study determining predictors of subjective health status 10 years post-PCI.

Long-term invasive follow-up of the everolimus-eluting bioresorbable vascular scaffold: five-year results of multiple invasive imaging modalities.

AIMS: Invasive imaging modalities have shown restoration of vasomotion, prevention of restenosis and, most importantly, increase in lumen area between six months and two years after first-generation everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) implantation. Our aim was to assess whether these positive findings were sustained in the long term. METHODS AND RESULTS: Patients included in the ABSORB cohort A from the Thoraxcenter Rotterdam cohort underwent coronary catheterisation including angiography, intravascular ultrasound (IVUS), virtual histology, optical coherence tomography (OCT) and vasomotion testing at five years. Eight out of 16 patients underwent catheterisation and scaffold assessment with multiple imaging modalities. A trend towards an increase in minimum luminal diameter was observed between two and five years by angiography (1.95±0.37 mm vs. 2.14±0.38 mm; p=0.09). IVUS data showed an increase in mean lumen area at five years (6.96±1.13 mm2) compared to six months (6.17±0.74 mm2; p=0.06) and two years (6.56±1.16 mm2; p=0.12), primarily due to a persistent reduction in plaque area size between six months and five years (9.17±1.86 mm2 vs. 7.57±1.63 mm2; p=0.03). The necrotic core area was reduced at five years compared to post-procedural results. In OCT, an increase in mean and minimal luminal area was observed. Moreover, no scaffold struts could be identified and a smooth endoluminal lining was observed. The scaffolded coronary segment did not show signs of endothelial dysfunction with acetylcholine testing. CONCLUSIONS: At five years, the Absorb BVS is no longer discernible by any invasive imaging method and endothelial function is restored. Late luminal enlargement persists up to five years of follow-up without adaptive vessel remodelling.

Comparison of long-term outcomes in STEMI and NSTE-ACS after coronary stent placement: an analysis in a real world BMS and DES population.

BACKGROUND/OBJECTIVES: The prognostic difference between STEMI and NSTE-ACS after coronary stent placement remains unclear. We aimed to compare the short- and long-term event rates in patients presenting with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) after percutaneous coronary intervention (PCI) with either bare-metal stents (BMS) or drug-eluting stents (DES). METHODS: Between 2000 and 2005 a total of 1749 STEMI and 1921 NSTE-ACS patients received either a BMS or DES in consecutive real world cohorts. Descriptive statistics and multivariate survival analyses were applied to compare the event rates in STEMI and NSTE-ACS during 4 years follow-up. RESULTS: NSTE-ACS patients had significantly higher clinical and angiographic risk profiles at baseline and were treated with less optimal medical therapy during follow-up. At 4 years follow-up, all-cause mortality was significantly higher in STEMI compared to NSTE-ACS after coronary stent placement (17.4% vs. 14.3%; HR 1.60, 95% CI 1.24-2.07). In a landmark analysis no difference was seen in all-cause mortality among STEMI en NSTE-ACS between 1 month and 4 years follow-up (HR 1.10, 95% CI 0.81-1.51). Cardiac death was more prevalent in STEMI patients, while the 4-year cumulative incidences of any myocardial infarction, any coronary revascularization, target lesion revascularization and definite stent thrombosis were similar in both ACS groups. CONCLUSIONS: Patients presenting with STEMI have a worse long-term prognosis compared to NSTE-ACS after coronary stent placement, due to higher short-term death rates. However, after the first month STEMI and NSTE-ACS patients have a comparable long-term survival.

Beta blocker therapy is associated with reduced depressive symptoms 12 months post percutaneous coronary intervention.

BACKGROUND: Beta blocker therapy may induce depressive symptoms, although current evidence is conflicting. We examined the association between beta blocker therapy and depressive symptoms in percutaneous coronary intervention (PCI) patients and the extent to which there is a dose-response relationship between beta blocker dose and depressive symptoms. METHODS: Patients treated with PCI (N=685) completed the depression scale of the Hospital Anxiety and Depression Scale 1 and 12 months post PCI. Information about type and dose of beta blocker use was extracted from medical records. RESULTS: Of all patients, 68% (466/685) were on beta blocker therapy at baseline. In adjusted analysis, beta blocker use at 1 month post PCI (OR: 0.82; 95% CI: 0.53-1.26) was not significantly associated with depressive symptoms. At 12 months post PCI, there was a significant relationship between beta blocker use and depressive symptoms (OR: 0.51; 95% CI: 0.31-0.84), with beta blocker therapy associated with a 49% risk reduction in depressive symptoms. There was a dose-response relationship between beta blocker dose and depressive symptoms 12 months post PCI, with the risk reduction in depressive symptoms in relation to a low dose being 36% (OR: 0.64; 95% CI: 0.37-1.10) and 58% (OR: 0.42; 95% CI: 0.24-0.76) in relation to a high dose. CONCLUSIONS: Patients treated with beta blocker therapy were less likely to experience depressive symptoms 12 months post PCI, with there being a dose-response relationship with a higher dose providing a more pronounced protective effect.

Analysis of 1 year virtual histology changes in coronary plaque located behind the struts of the everolimus eluting bioresorbable vascular scaffold.

Serial intravascular ultrasound virtual histology (IVUS-VH) after implantation of metallic stents has been unable to show any changes in the composition of the scaffolded plaque overtime. The everolimus-eluting ABSORB scaffold potentially allows for the formation of new fibrotic tissue on the scaffolded coronary plaque during bioresorption. We examined the 12 month IVUS-VH changes in composition of the plaque behind the struts (PBS) following the implantation of the ABSORB scaffold. Using IVUS-VH and dedicated software, the composition of the PBS was analyzed in all patients from the ABSORB Cohort B2 trial, who were imaged with a commercially available IVUS-VH console (s5i system, Volcano Corporation, Rancho Cordova, CA, USA), immediately post-ABSORB implantation and at 12 month follow-up. Paired IVUS-VH data, recorded with s5i system, were available in 17 patients (18 lesions). The analysis demonstrated an increase in mean PBS area (2.39 ± 1.85 mm(2) vs. 2.76 ± 1.79 mm(2), P = 0.078) and a reduction in the mean lumen area (6.37 ± 0.90 mm(2) vs. 5.98 ± 0.97 mm(2), P = 0.006). Conversely, a significant decrease of 16 and 30% in necrotic core (NC) and dense calcium (DC) content, respectively, were evident (median % NC from 43.24 to 36.06%, P = 0.016; median % DC from 20.28 to 11.36%, P = 0.002). Serial IVUS-VH analyses of plaque located behind the ABSORB struts at 12-month demonstrated an increase in plaque area with a decrease in its NC and DC content. Larger studies are required to investigate the clinical impact of these findings.

The impact of patient and lesion complexity on clinical and angiographic outcomes after revascularization with zotarolimus- and everolimus-eluting stents: a substudy of the RESOLUTE All Comers Trial (a randomized comparison of a zotarolimus-eluting stent with an everolimus-eluting stent for percutaneous coronary intervention).

OBJECTIVES: The aim of this study was to investigate the impact of patient and lesion complexity on outcomes with newer-generation zotarolimus-eluting stents (ZES) and everolimus-eluting stents (EES). BACKGROUND: Clinical and angiographic outcomes of newer-generation stents have not been described among complex patients. METHODS: Patients enrolled in the RESOLUTE All Comers trial (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) were stratified into "complex" and "simple." RESULTS: Of 2,292 patients, 1,520 (66.3%) were complex and treated with ZES (n = 764) or EES (n = 756). Event rates were higher among complex patients, and results did not differ between ZES and EES, regardless of complexity. At 1 year, target lesion failure was 8.9% in ZES- and 9.7% in EES-treated complex patients (p = 0.66) and 6.8% in ZES- and 5.7% in EES-treated simple patients (p = 0.55). Rates of cardiac death (1.3% vs. 2.2%, p = 0.24), target-vessel myocardial infarction (4.3% vs. 4.4%, p = 0.90), and clinically indicated target lesion revascularization (4.4% vs. 4.0%, p = 0.80) were similar for both stent types among complex patients. Definite or probable stent thrombosis occurred in 20 (1.3%) complex patients with no difference between ZES (1.7%) and EES (0.9%, p = 0.26). Angiographic follow-up showed similar results for ZES and EES in terms of in-stent percentage diameter stenosis (22.2 ± 15.4% vs. 21.4 ± 15.8%, p = 0.67) and in-segment binary restenosis (6.6% vs. 8.0%, p = 0.82) in the complex group. CONCLUSIONS: In this all-comers randomized trial, major adverse cardiovascular events were more frequent among complex than simple patients. The newer-generation ZES and EES proved to be safe and effective, regardless of complexity, with similar clinical and angiographic outcomes for both stent types through 1 year. (RESOLUTE-III All Comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention; NCT00617084).

Relation between plaque type and dissections at the edges after stent implantation: an optical coherence tomography study.

BACKGROUND: Stent implantation can create vessel damage such as edge dissections. The objectives were i) to evaluate the frequency of edge dissections after stenting visible by intracoronary optical coherence tomography (OCT) in comparison with angiography. ii) to assess with OCT the plaque type left at the stent edges after implantation, and iii) to study whether there is an association between plaque type and dissections at stent edges. METHODS: Seventy-three consecutive patients (80 vessels) with OCT post-stent implantation were included in the study. By OCT, plaque type at stent edges and presence of edge dissection were assessed. Angiograms were analyzed by two independent observers to assess the presence of edge dissections. RESULTS: Distal and proximal edges were visible by OCT in 72/80 and 45/80 vessels respectively. OCT and angiography agreed in the detection of 7 dissections at distal edge (κ=0.32) and 1 dissection at proximal edge (κ=0.22). Plaque type at distal edge was: fibrotic 55.6%, fibrocalcific 22.2%, fibroatheroma 15.3% and thin-cap fibroatheroma (TCFA) 6.9%. At proximal edge plaque type was: fibrotic 31.1%, fibrocalcific 33.3%, fibroatheroma 28.9% and TCFA 6.7%. In the distal edge, presence of edge dissection was significantly more frequent when the plaque type at the edge was fibrocalcific (43.8%) or lipid rich (37.5%) than when the plaque was fibrous (10%) p=0.009. CONCLUSIONS: OCT showed higher sensitivity compared to angiography for the identification of edge dissections. A high proportion of patients showed lipid-rich plaques at stent edges. Plaque type at the stent edges has impact on the presence of edge dissections.

The use of MSCT for the evaluation of the aortic root before transcutaneous aortic valve implantation: the Rotterdam approach.

AIMS: Whereas transthoracic echocardiography is the modality of choice for the diagnosis of severe aortic stenosis and cine-fluoroscopy is used to guide the implantation of the TAVI prosthesis, we believe that multislice computer tomography (MSCT) is the modality of choice for evaluation of the aortic root with a view to selecting patients with suitable anatomy and to guide sizing. We aim to describe an anatomical approach for the step by step interrogation of a 3D MSCT dataset to obtain the measurements of the aortic root required for patient selection, sizing and selection of the optimal angulation of the C-arm during the implantation procedure. METHODS AND RESULTS: The landmarks used to anatomically define the aortic annulus and structures of the aortic root may be used to define the same structures for measurement on a 3D MSCT dataset by setting up orthogonal cut-planes including one axial to the aortic annulus. This allows true axial diameter measurements and also enables us to define the valve plane. CONCLUSIONS: Measurement on the axial images avoids incorrect diameter measurements that do not pass through the central axis.

Optical coherence tomography in patients with acute coronary syndrome.

Optical coherence tomography (OCT) is a novel invasive imaging technology that allows in vivo assessment of the coronary wall with high resolution (approximately 15 micron). OCT offers a number of specific diagnostic features to study culprit lesions in patients suffering from acute coronary syndrome (ACS). Clinical OCT studies in patients presenting with ACS were able to confirm post mortem histopathology findings and shed light on the dynamic nature of atherosclerotic plaque formation, modification and rupture. OCT confirmed in vivo that the incidence of target lesion and remote TCFA varies with the clinical syndrome of the patients, being most pronounced in patients with acute myocardial infarction as compared to patients with stable angina. In culprit lesions where rupture of a fibrous cap has been documented, the fibrous cap thickness was in the range of 50 micron and macrophage density was elevated. Encouraging small scale clinical studies evaluated treatment effects in this population. OCT was used to demonstrate statin effects on fibrous cap thickness or the effects of different stent designs. The markedly improved image quality and user-friendliness of the second generation, Fourier-domain OCT, will allow large scale clinical application and thus, will increase our understanding of the pathophysiology and the prevention of ACS.

Three dimensional evaluation of the aortic annulus using multislice computer tomography: are manufacturer's guidelines for sizing for percutaneous aortic valve replacement helpful?

AIMS: To evaluate the effects of applying current sizing guidelines to different multislice computer tomography (MSCT) aortic annulus measurements on Corevalve (CRS) size selection. METHODS AND RESULTS: Multislice computer tomography annulus diameters [minimum: D(min); maximum: D(max); mean: D(mean) = (D(min) + D(max))/2; mean from circumference: D(circ); mean from surface area: D(CSA)] were measured in 75 patients referred for percutaneous valve replacement. Fifty patients subsequently received a CRS (26 mm: n = 22; 29 mm: n = 28). D(min) and D(max) differed substantially [mean difference (95% CI) = 6.5 mm (5.7-7.2), P < 0.001]. If D(min) were used for sizing 26% of 75 patients would be ineligible (annulus too small in 23%, too large in 3%), 48% would receive a 26 mm and 12% a 29 mm CRS. If D(max) were used, 39% would be ineligible (all annuli too large), 4% would receive a 26 mm, and 52% a 29 mm CRS. Using D(mean), D(circ), or D(CSA) most patients would receive a 29 mm CRS and 11, 16, and 9% would be ineligible. In 50 patients who received a CRS operator choice corresponded best with sizing based on D(CSA) and D(mean) (76%, 74%), but undersizing occurred in 20 and 22% of which half were ineligible (annulus too large). CONCLUSION: Eligibility varied substantially depending on the sizing criterion. In clinical practice both under- and oversizing were common. Industry guidelines should recognize the oval shape of the aortic annulus.

Geometry and degree of apposition of the CoreValve ReValving system with multislice computed tomography after implantation in patients with aortic stenosis.

OBJECTIVES: Using multislice computed tomography (MSCT), we sought to evaluate the geometry and apposition of the CoreValve ReValving System (CRS, Medtronic, Luxembourgh, Luxembourgh) in patients with aortic stenosis. BACKGROUND: There are no data on the durability of percutaneous aortic valve replacement. Geometric factors may affect durability. METHODS: Thirty patients had MSCT at a median 1.5 months (interquartile range [IQR] 0 to 7 months) after percutaneous aortic valve replacement. Axial dimensions and apposition of the CRS were evaluated at 4 levels: 1) the ventricular end; 2) the nadir; 3) central coaptation of the CRS leaflets; and 4) commissures. Orthogonal smallest and largest diameters and cross-sectional surface area were measured at each level. RESULTS: The CRS (26-mm: n = 14, 29-mm: n = 16) was implanted at 8.5 mm (IQR 5.2 to 11.0 mm) below the noncoronary sinus. None of the CRS frames reached nominal dimensions. The difference between measured and nominal cross-sectional surface area at the ventricular end was 1.6 cm(2) (IQR 0.9 to 2.6 cm(2)) and 0.5 cm(2) (IQR 0.2 to 0.7 cm(2)) at central coaptation. At the level of central coaptation the CRS was undersized relative to the native annulus by 24% (IQR 15% to 29%). The difference between the orthogonal smallest and largest diameters (degree of deformation) at the ventricular end was 4.4 mm (IQR 3.3 to 6.4 mm) and it decreased progressively toward the outflow. Incomplete apposition of the CRS frame was present in 62% of patients at the ventricular end and was ubiquitous at the central coaptation and higher. CONCLUSIONS: Dual-source MSCT demonstrated incomplete and nonuniform expansion of the CRS frame, but the functionally important mid-segment was well expanded and almost symmetrical. Undersizing and incomplete apposition were seen in the majority of patients.