Abluminal Neointimal Healing by Optical Coherence Tomography Assessment After Drug-Eluting Stent Implantation on Organized Recanalized Thrombus.

Six-month PCI follow-up results of left anterior descending (LAD) and circumflex (CX) drug-eluting stent implantation are presented. Angiography showed patent LAD and CX stents. However, OCT revealed almost all abluminal cavities were completely filled, which the authors surmise was due to a neointimal healing process.

Optimal P2Y12 Inhibitor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Network Meta-Analysis.

OBJECTIVES: The study sought to compare the clinical efficacy and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PPCI). BACKGROUND: Limited data exist regarding the comparative efficacy and safety of P2Y12 inhibitors in STEMI patients undergoing PPCI. METHODS: Clinical trials enrolling STEMI patients were identified and relevant data was extracted. Major adverse cardiovascular events (MACE) were defined as the composite of all cause mortality, MI, and target vessel revascularization. Network meta-analysis was performed using Bayesian methods. RESULTS: A total of 37 studies with 88,402 STEMI patients and 5,077 MACE were analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that prasugrel was associated with: lower MACE than clopidogrel (standard dose odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.50 to 0.69; high-dose OR: 0.60, 95% CI: 0.51 to 0.71; upstream OR: 0.79, 95% CI: 0.66 to 0.94), and ticagrelor (standard dose OR: 0.69, 95% CI: 0.56 to 0.84; upstream OR: 0.72, 95% CI: 0.50 to 1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower stroke risk than standard clopidogrel and standard or upstream ticagrelor; and lower stent thrombosis than standard or upstream clopidogrel. At 1-year (10 studies, n = 40,333) prasugrel was associated with lower mortality and MACE than other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies where patients received bivalirudin, drug-eluting stents, and but not glycoprotein IIb/IIIa inhibitor. CONCLUSIONS: In STEMI patients undergoing PPCI, prasugrel and ticagrelor are more efficacious than clopidogrel; in addition, prasugrel was superior to ticagrelor particularly in conjunction with bivalirudin and drug-eluting stents.

Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial).

Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow-up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT-AF.

Causes, assessment, and treatment of stent thrombosis--intravascular imaging insights.

Stent thrombosis is a rare, but serious, complication of percutaneous coronary intervention and is associated with severe morbidity and mortality. In addition to clinical and pathological studies, intravascular imaging has advanced our understanding of the mechanisms underlying stent thrombosis. In particular, intravascular imaging has been used to study stent underexpansion, malapposition, uncovered struts, and neoatherosclerosis as risk factors for stent thrombosis. Intravascular ultrasonography and optical coherence tomography can be used to guide stent implantation and minimize the risk of stent thrombosis. Additionally, optical coherence tomography offers the unique potential to tailor treatment of stent thrombosis to address the specific mechanism underlying the thrombotic event. Bioresorbable stent technologies have been introduced with the goal of further reducing the incidence of stent thrombosis, and intravascular imaging has had an integral role in the development and assessment of these new devices. In this Review, we present insights gained through intravascular imaging into the causes of stent thrombosis, and the potential utility of intravascular imaging in the optimization of stent deployment and treatment of stent thrombosis events.

Optical coherence tomography assessment and quantification of intracoronary thrombus: Status and perspectives.

Coronary angiography is the "golden standard" imaging technique in interventional cardiology and it is still widely used to guide interventions. A major drawback of this technique, however, is that it is inaccurate in the evaluation and quantification of intracoronary thrombus burden, a critical prognosticator and predictor of intraprocedural complications in acute coronary syndromes. The introduction of optical coherence tomography (OCT) holds the promise of overcoming this important limitation, as near-infrared light is uniquely sensitive to hemoglobin, the pigment of red blood cells trapped in the thrombus. This narrative review will focus on the use of OCT for the assessment, evaluation and quantification of intracoronary thrombosis.

Intra-coronary thrombus evolution during acute coronary syndrome: regression assessment by serial optical coherence tomography analyses.

AIMS: We investigated the feasibility of thrombus quantification by frequency-domain optical coherence tomography (FD-OCT) methods in patients with highly thrombotic acute coronary syndrome (ACS) treated by deferred stenting strategy. METHODS AND RESULTS: Patients were suitable for inclusion if they presented (i) an ACS that was successfully revascularized by manual thrombo-aspiration and (ii) a large residual thrombus on coronary angiography and initial FD-OCT analysis. These patients underwent a second procedure including FD-OCT analysis after several days of optimal antithrombotic therapy. Serial area measurements within the athero-thrombotic culprit lesion were performed to evaluate the OCT-thrombus score, volume, and length. Sixteen patients (88% men/age = 59.3 ± 4.1 years/94% STEMI) were included in the study. The mean delay between OCT analyses was 3.9 ± 0.3 day. No adverse event was observed during this interval. We observed a reduction of thrombus burden between the two analyses, as assessed by the significant reductions in OCT-thrombus score (22.3 ± 2.6 vs. 10.3 ± 1.3, P < 0.001), OCT-thrombus volume (9.6 ± 2.3 vs. 3.6 ± 0.9 mm(3), P = 0.003), and OCT-thrombus length (11.1 ± 1.4 vs. 7.4 ± 0.8 mm, P = 0.01). The percentages of OCT-thrombus score and volume reduction were highly correlated with the inter-OCT analyses delay (respectively ρ = 0.65 and ρ = 0.84, P < 0.01 for both). CONCLUSION: FD-OCT assessment of thrombus volume in selected ACS patients is feasible, safe, and could allow clot regression monitoring in vivo.

Mechanisms of atherothrombosis and vascular response to primary percutaneous coronary intervention in women versus men with acute myocardial infarction: results of the OCTAVIA study.

OBJECTIVES: This study sought to assess in vivo sex differences in the pathophysiology of ST-segment elevation myocardial infarction (STEMI) and vascular response to primary percutaneous coronary intervention (PCI). BACKGROUND: There is no consensus on whether differences in the pathophysiology of STEMI and response to primary PCI between women and men reflect biological factors as opposed to differences in age. METHODS: In this prospective, multicenter study, 140 age-matched men and women with STEMI undergoing primary PCI with everolimus-eluting stent were investigated with intravascular optical coherence tomography, histopathology-immunohistochemistry of thrombus aspirates, and serum biomarkers. Primary endpoints were the percentages of culprit plaque rupture at baseline and everolimus-eluting stent strut coverage at 9-month follow-up as determined by optical coherence tomography. RESULTS: Men and women had similar rates of plaque rupture (50.0% vs. 48.4%; risk ratio [RR]: 1.03; 95% confidence interval [CI]: 0.73 to 1.47; p = 0.56). Nonruptured/eroded plaques comprised 25% of all cases (p = 0.86 in men vs. women). There were no sex differences in composition of aspirated thrombus and immune and inflammatory serum biomarkers. At 9 months, women had similar strut coverage (90.9% vs. 92.5%; difference in medians: RR: 0.2%; 95% CI: -0.4% to 1.3%; p = 0.89) and amount of in-stent neointimal obstruction (10.3% vs. 10.6%; p = 0.76) as men did. There were no sex differences in clinical outcome either at 30-day or 1-year follow-up. CONCLUSIONS: In patients presenting with STEMI undergoing primary PCI, no differences in culprit plaque morphology and factors associated with coronary thrombosis were observed between age-matched men and women. Women also showed similar vascular healing response to everolimus-eluting stents as men did. (Optical Coherence Tomography Assessment of Gender Diversity In Primary Angioplasty: The OCTAVIA Trial [OCTAVIA]; NCT01377207).

Assessment of plasma aminothiol levels and the association with recurrent atherothrombotic events in patients hospitalized for an acute coronary syndrome: a prospective study.

BACKGROUND: The aminothiols homocysteine and, to a lesser extent, cysteine have been associated with adverse cardiovascular outcome, whereas glutathione, as an antioxidant, may protect against atherosclerosis and thrombosis. Potentially, the combined assessment of these aminothiols may provide a more accurate association with future cardiovascular outcome. We evaluated the association between recurrent atherothrombotic events and the concentration of total plasma cysteine, homocysteine, and glutathione and their combination. METHODS: Respective aminothiols were measured by high-performance liquid chromatography in blood plasma of consecutive first-day survivors admitted for an acute coronary syndrome between April 2002 and January 2004. The combined score was calculated using the combination of the individual aminothiols. The end point was the composite of cardiovascular death, myocardial infarction, and/or stroke. RESULTS: A cohort of 375 consecutive patients (median age 66 years, 66% male) were followed for a median duration of 2.7 years. The end point occurred in 82 patients (22%). In univariate analyses, all aminothiols were significantly associated with the composite end point. After correction for possible confounders, only cysteine and glutathione remained significantly associated. The strongest association with the end point was observed for the combined score (adjusted hazard ratio, 1.40 per standard deviation increase; p=0.005). CONCLUSIONS: Although homocysteine is generally considered the aminothiol of interest with respect to cardiovascular disease, in our prospective study, only cysteine and glutathione appeared independently associated with recurrent atherothrombotic events. Moreover, we showed that an imbalance in the combination of aminothiols could be of more importance than investigating the individual metabolites.

First serial assessment at 6 months and 2 years of the second generation of absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study.

BACKGROUND: Nonserial observations have shown this bioresorbable scaffold to have no signs of area reduction at 6 months and recovery of vasomotion at 1 year. Serial observations at 6 months and 2 years have to confirm the absence of late restenosis or unfavorable imaging outcomes. METHODS AND RESULTS: The ABSORB trial is a multicenter single-arm trial assessing the safety and performance of an everolimus-eluting bioresorbable vascular scaffold. Forty-five patients underwent serial invasive imaging, such as quantitative coronary angiography, intravascular ultrasound, and optical coherence tomography at 6 and 24 months of follow-up. From 6 to 24 months, late luminal loss increased from 0.16±0.18 to 0.27±0.20 mm on quantitative coronary angiography, with an increase in neointima of 0.68±0.43 mm(2) on optical coherence tomography and 0.17±0.26 mm(2) on intravascular ultrasound. Struts still recognizable on optical coherence tomography at 2 years showed 99% of neointimal coverage with optical and ultrasonic signs of bioresorption accompanied by increase in mean scaffold area compared with baseline (0.54±1.09 mm(2) on intravascular ultrasound, P=0.003 and 0.77±1.33 m(2) on optical coherence tomography, P=0.016). Two-year major adverse cardiac event rate was 6.8% without any scaffold thrombosis. CONCLUSIONS: This serial analysis of the second generation of the everolimus-eluting bioresorbable vascular scaffold confirmed, at medium term, the safety and efficacy of the new device. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856856.

Quantitative optical frequency domain imaging assessment of in-stent structures in patients with ST-segment elevation myocardial infarction: impact of imaging sampling rate.

BACKGROUND: The impact of the sampling rate (SR) of optical frequency domain imaging (OFDI) on quantitative assessment of in-stent structures (ISS) such as plaque prolapse and thrombus remains unexplored. METHODS AND RESULTS: OFDI after stenting was performed in ST-segment elevation myocardial infarction (STEMI) patients using a TERUMO OFDI system (Terumo Europe, Leuven, Belgium) with 160 frames/s and pullback speed of 20 mm/s. A total of 126 stented segments were analyzed. ISS were classified as either attached or non-attached to stent area boundaries. The volume, mean area and largest area of ISS were assessed according to 4 frequencies of SR, corresponding to distances between the analyzed frames of 0.125, 0.25, 0.50 and 1.0 mm. ISS volume was calculated by integrating cross-sectional ISS areas multiplied by each sampling distance using the disk summation method. The volume and mean area of ISS became significantly larger, while the largest area became significantly smaller as sampling distance became larger (1.11 mm(2) for 0.125 mm vs. 1.00 mm(2) for 1.0 mm, P for trend=0.036). In addition, variance of difference was positively associated with increasing width of sampling distance. CONCLUSIONS: Quantification of ISS is significantly influenced by the applied frequency of SR. This should be taken into account when designing future OFDI studies in which quantitative assessment of ISS is critical for the evaluation of STEMI patients.

Real-time assessment of cardiac perfusion, coronary angiography, and acute intravascular thrombi using dual-channel near-infrared fluorescence imaging.

OBJECTIVES: We have developed an image-guided surgical system based on invisible near-infrared fluorescent light. Presently, the only clinically available near-infrared fluorophore is indocyanine green, which fluoresces at approximately 800 nm and is used for coronary angiography. Our objective was to determine whether methylene blue, already US Food and Drug Administration approved for other indications, has useful near-infrared fluorescence properties for image-guided cardiac surgery. METHODS: The optical properties of methylene blue were measured after dissolution in 100% serum. Biodistribution and clearance were quantified in organs and tissue after intravenous bolus injection of 2 mg/kg methylene blue in 3 rats. Coronary arteriography and cardiac perfusion were imaged in real time after intravenous bolus injection of 1 mg/kg methylene blue in 5 pigs with coronary obstructions. Coronary angiography and acute thrombi were assessed by using 800-nm fluorophores, indocyanine green, and IR-786-labeled platelets, respectively. RESULTS: The peak absorbance and emission of methylene blue as a near-infrared fluorophore occur at 667 nm and 686 nm, respectively. After intravenous injection, methylene blue provides highly sensitive coronary angiography. A lipophilic cation, methylene blue is extracted rapidly into tissue, with myocardium displaying unusually high uptake. Methylene blue permits real-time visualization and quantitative assessment of myocardial perfusion. Because of absent spectral overlap, use of 2 independent fluorophores in our imaging system permits simultaneous quantification of perfusion, venous drainage, and/or intravascular thrombi. CONCLUSIONS: Methylene blue is an effective near-infrared fluorophore that provides direct visualization of coronary arteriography and cardiac perfusion. In conjunction with approximately 800-nm near-infrared fluorophores, important functional assessments during cardiac surgery are also possible.

Coronary stent assessment with 64-slice multislice computed tomography: a literature review.

Coronary in-stent restenosis (ISR) and thrombosis cause recurrent cardiac ischemia, require repeat investigations, and have significant clinical and financial implications. As coronary stenting becomes widespread, the number of patients with recurrent ischemia is increasing. ISR and thrombosis occur in up to 10 and 0.8%, respectively, of patients with drug-eluting stents. A noninvasive investigation for symptomatic stented patients is required to identify stent thrombosis, ISR, and de novo lesions in native coronary arteries. The difficulties in using computed tomography to image high-density materials adjacent to moving calcified vessels have been reduced with advances in spatial and temporal resolution and reconstruction software. This review examines the advantages and disadvantages of 64-slice multislice computed tomography for coronary stent evaluation, explaining the diagnostic difficulties and outlining techniques to optimize diagnostic accuracy.

Angiographic, ultrasonic, and angioscopic assessment of the coronary artery wall and lumen area configuration after directional atherectomy: the mechanism revisited.

The purpose of the present study was to use the complementary information of angiography, intravascular ultrasound, and intracoronary angioscopy before and after directional atherectomy to characterize the postatherectomy appearance of vessel wall contours and the mechanism of lumen enlargement. Directional coronary atherectomy aims at debulking rather than dilating a coronary artery lesion. The selective removal of the plaque may potentially minimize the vessel wall damage and lead to subsequent better late outcome. Whether plaque removal is the main mechanism of action has only to be assessed indirectly by angiography and warrants further investigation with detailed analysis of luminal changes and vessel wall damage by ultrasound and direct visualization with angioscopy. Twenty-six patients have been investigated by quantitative angiography, intravascular ultrasound, and intracoronary angioscopy (n = 19) before and after atherectomy. In addition, all retrieved specimens were microscopically examined. Ultrasound imaging showed an increase in lumen area from 1.95 +/- 0.70 mm2 to 7.86 +/- 2.16 mm2 at atherectomy. The achieved gain mainly resulted from plaque removal because plaque plus media area decreased from 18.16 +/- 4.47 mm2 to 13.13 +/- 3.10 mm2. Vessel wall stretching (i.e., change in external elastic lamina area) accounted for only 15% of lumen area gain. Luminal gain was higher in noncalcified (6.52 +/- 2.12 mm2) lesions than in lesions containing deeply located calcium (5.19 +/- 0.99 mm2) and lowest in superficially calcified lesions (5.41 +/- 2.41 mm2). Ultrasound imaging identified an atherectomy byte in 85% of the cases, whereas angioscopy revealed such a crevice in 74%. The complementary use of the three techniques revealed an underestimation of the presence of dissection/tear and new thrombus by angiography (10% and 4%) and ultrasound imaging (12% and 0%) compared with angioscopy (26% and 21%). The combined use of angiography, ultrasound, and angioscopy reveals that the postatherectomy luminal lining is not as regular and smooth as that seen by angiography. Luminal enlargement with atherectomy is achieved by plaque excision rather than arterial expansion.

Part XII: Assessment of serial lesions in the proximal right coronary artery following intracoronary thrombolysis.

Assessment of angiographically serial coronary lesions at the time of diagnostic catheterization remains a difficult clinical problem. Doppler flow velocity data is easily obtainable and allows physiologic interrogation of the distal coronary microcirculation, but has limitations in the detection of some flow-limiting stenoses. In cases of serial lesions or distal arterial disease, particularly after thrombolysis, flow velocity data may be insufficient to identify the hemodynamic significance of the coronary lesions. Translesional pressure measurements may be combined with flow velocity data to support an appropriate physiologically based therapeutic approach.