Comparison of endothelial shear stress between ultrathin strut bioresorbable polymer drug-eluting stent vs durable-polymer drug-eluting stent post-stent implantation: An optical coherence tomography substudy from BIOFLOW II.

BACKGROUND: Recent clinical data indicate a different performance of biodegradable polymer (BP)-drug eluting stent (DES) compared to durable polymer (DP)-DES. Whether this can be explained by a beneficial impact of BP-DES stent design on the local hemodynamic forces distribution remains unclear. OBJECTIVES: To compare endothelial shear stress (ESS) distribution after implantation of ultrathin (us) BP-DES and DP-DES and examine the association between ESS and neointimal thickness (NIT) distribution in the two devices at 9 months follow up. METHODS AND RESULTS: We retrospectively identified patients from the BIOFLOW II trial that had undergone OCT imaging. OCT data were utilized to reconstruct the surface of the stented segment at baseline and 9 months follow-up, simulate blood flow, and measure ESS and NIT in the stented segment. The patients were divided into 3 groups depending on whether DP-DES (N = 8, n = 56,160 sectors), BP-DES with a stent diameter of >3 mm (strut thickness of 80 µm, N = 6, n = 36,504 sectors), or BP-DES with a stent diameter of ≤3 mm (strut thickness of 60 µm, N = 8, n = 50,040 sectors) were used for treatment. The ESS, and NIT distribution and the association of these two variables were estimated and compared among the 3 groups. RESULTS: In the DP-DES group mean NIT was 0.18 ± 0.17 mm and ESS 1.68 ± 1.66 Pa; for the BP-DES ≤3 mm group the NIT was 0.17 ± 0.11 mm and ESS 1.49 ± 1.24 Pa and for the BP-DES >3 mm group 0.20 ± 0.23 mm and 1.42 ± 1.24 Pa respectively (p < 0.001 for both NIT and ESS comparisons across groups). A negative correlation between NIT and baseline ESS was found, the correlation coefficient for all the stented segments was -0.33, p < 0.001. CONCLUSION: In this OCT sub-study of the BIOFLOW II trial, the NIT was statistically different between groups of patients treated with BP-DES and DP-DES. In addition, regions of low ESS were associated with increased NIT in all studied devices.

Temporal changes in coronary plaque as assessed by an artificial intelligence-based optical coherence tomography: from the first-in-human trial on DREAMS 3G scaffold.

AIMS: The aim of the study is to assess the impact of the baseline plaque composition on the DREAMS 3G luminal late loss and to compare the serial plaque changes between baseline and 6 and 12 months (M) follow-up. METHODS AND RESULTS: A total of 116 patients were enrolled in the BIOMAG-I trial. Patients were imaged with optical coherence tomography (OCT) pre- and post-DREAMS 3G implantation and at 6 and 12 M. OCTPlus software uses artificial intelligence to assess composition (i.e. lipid, calcium, and fibrous tissue) of the plaque. The differences between the OCT-derived minimum lumen area (MLA) post-percutaneous coronary intervention and 12 M were grouped into three terciles. Patients with larger MLA differences at 12 M (P = 0.0003) had significantly larger content of fibrous tissue at baseline. There was a reduction of 24.8% and 20.9% in lipid area, both P < 0.001, between the pre-DREAMS 3G OCT and the 6 and 12 M follow-up. Conversely, the fibrous tissue increased by 48.4% and 36.0% at 6 and 12 M follow-up, both P < 0.001. CONCLUSION: The larger the fibrous tissue in the lesion at baseline, the larger the luminal loss seen at 6 and 12 M. Following the implantation of DREAMS 3G, favourable healing of the vessel coronary wall occurs as shown by a decrease in the lipid area and an increase in fibrous tissue.

Comparison of Angiographic and Intravascular Ultrasound Vessel Measurements in Infra-Popliteal Endovascular Interventions: The Below-the-Knee Calibration Study.

BACKGROUND: Endovascular revascularization (ER) via percutaneous transluminal angioplasty (PTA) and stenting are viable options for revascularization in below-the-knee (BTK) peripheral arterial disease. Two-dimensional angiography has been the standard of practice for estimating vessel size and selecting treatment devices during ER. However, in other vascular territories, intravascular ultrasound (IVUS) offers better visualization of the lumen dimensions. PURPOSE: To compare angiographic and intravascular ultrasound reference vessel (lumen) measurements in below-the-knee peripheral artery interventions. METHODS: Twenty consecutive patients were enrolled in the BTK Calibration study from 2 sites in the United States and Australia. Patients with at least one diseased segment in a native infra-popliteal artery (below-the-knee) and a clinical indication for endovascular therapy (EVT) were included with no limitations with regard to vessel diameter or lesion length. Digital subtraction angiography and IVUS imaging were collected pre- and post-PTA and images were sent to an independent core lab for standardized quantitative analysis of the normal-looking reference vessel dimensions when available. The results were presented as least square means with 95% confidence intervals and a p-value of <0.05 was considered significant. RESULTS: The overall (N = 19) mean reference vessel diameter for QVA was 2.98 ± 1.24 mm vs. 3.47 ± 0.72 mm for IVUS (mean difference was -0.50 mm, (95% CI: -0.80, -0.20; p = 0.14). As expected, in the proximal segments (N = 12), the mean reference vessel diameters were larger: for QVA, it was 3.17 ± 1.34 mm vs. 3.55 ± 0.76 mm in IVUS, (mean difference was -0.38 mm, (95% CI: -0.79, 0.03; p = 0.40); while in the distal segments (N = 7), mean reference vessel diameters were smaller: for QVA, it was 2.64 ± 1.06 mm vs. 3.33 ± 0.67 mm in IVUS, (mean difference was -0.69 mm, (95% CI: -1.04, 0.34; p = 0.17). We observed a greater degree of acute gain in cases where the treatment balloon size correlated with the IVUS measured reference size. CONCLUSION: Angiography underestimates infrapopliteal reference vessel lumen size even when quantitatively assessed. Adjunctive IVUS imaging use in guiding BTK procedures could help ensure adequate sizing and possibly impact immediate post-procedure indices.

Human vs. machine vs. core lab for the assessment of coronary atherosclerosis with lumen and vessel contour segmentation with intravascular ultrasound.

A machine learning (ML) algorithm for automatic segmentation of intravascular ultrasound was previously validated. It has the potential to improve efficiency, accuracy and precision of coronary vessel segmentation compared to manual segmentation by interventional cardiology experts. The aim of this study is to compare the performance of human readers to the machine and against the readings from a Core Laboratory. This is a post-hoc, cross-sectional analysis of the IBIS-4 study. Forty frames were randomly selected and analyzed by 10 readers of varying expertise two separate times, 1 week apart. Their measurements of lumen, vessel, plaque areas, and plaque burden were performed in an offline software. Among humans, the intra-observer variability was not statistically significant. For the total 80 frames, inter-observer variability between human readers, the ML algorithm and Core Laboratory for lumen area, vessel area, plaque area and plaque burden were not statistically different. For lumen area, however, relative differences between the human readers and the Core Lab ranged from 0.26 to 12.61%. For vessel area, they ranged from 1.25 to 9.54%. Efficiency between the ML algorithm and the readers differed notably. Humans spent 47 min on average to complete the analyses, while the ML algorithm took on average less than 1 min. The overall lumen, vessel and plaque means analyzed by humans and the proposed ML algorithm are similar to those of the Core Lab. Machines, however, are more time efficient. It is warranted to consider use of the ML algorithm in clinical practice.

Comparison of Quantitative Flow Ratio and Invasive Physiology Indices in a Diverse Population at a Tertiary United States Hospital.

BACKGROUND: Quantitative flow ratio (QFR) is a technology to evaluate the coronary stenosis significance on 3-dimensional quantitative coronary angiography. The aim of this study is to evaluate and compare the QFR versus fractional flow reserve (FFR) and/or instantaneous free-wave ratio (iFR) in a US population with a fair African American population representation. METHODS AND RESULTS: This was a retrospective, observational and single-center study that enrolled 100 patients who underwent coronary angiography. The diagnostic performance of QFR in terms of sensitivity was 0.80 (95%CI 0.64-0.97) and specificity was 0.95 (95% CI 0.90-1.00), the positive predictive value (PPV) was 0.83 (0.68-0.98), while the negative predictive value (NPV) was 0.94 (0.88-0.99). The overall accuracy was 0.91 and area under the curve (AUC) was 0.92 (95% CI 0.87-0.97). The R-squared was 0.54 and the Bland-Altman plot showed a bias of 0.0016 (SD 0.063) and limits of agreement (LOA): Upper LOA 0.13 and Lower LOA -0.12. In African Americans (n = 33), accuracy, AUC, sensitivity, specificity (94%; 0.90 [0.80-1.00]; 0.90 [0.71-1.00]; 0.96 [0.87-1.00], respectively) were better than those for the overall population. CONCLUSIONS: In a US-based representative population, vessel QFR accuracy and agreement with FFR as reference is high. Diagnostic performance of QFR in African Americans is also excellent.

Optical Coherence Tomography based treatment approach for patients with Acute Coronary Syndrome.

INTRODUCTION: Areas covered:In this review, we outline the underlying causes of acute coronary syndrome (ACS) as evaluated by optical coherence tomography (OCT). We report both the definitions of each mechanism and its frequency as reported in the literature to date. Finally, we present an algorithm based on the findings in the review that gives an outlined approach to perform intervention on ACS patients.Expert opinion:Although the most common and most accepted intervention in ACS cases is stent implantation, data suggest a stentless approach in cases of plaque erosion, which generally occurs in younger patients presenting with an acute coronary syndrome that have TIMI flow of 2/3 and either a small or large burden of thrombus and underlying stenosis of less than 50%.

Comparison of Patterns of Coronary Artery Disease in Patients With Heart Failure by Cardiac Amyloidosis Status.

BACKGROUND/PURPOSE: The aim of this study is to characterize the pattern and the severity of coronary artery lesions in cardiac amyloidosis. METHODS: We retrospectively compared patients with heart failure who tested positive (i.e., biopsy or gene tests - HF/CA+) against those who tested negative (HF/CA-) for cardiac amyloidosis. Groups were compared demographically and angiographically for qualitative and quantitative variables to determine patterns of involvement in the major epicardial coronary vessels. RESULTS: The study included 110 heart failure patients, of whom 55 patients (88 lesions) were in the HF/CA+ group, and 55 patients (66 lesions) were HF/CA-. Despite the advanced age of HF/CA+ patients (74.5 ± 11.0 years vs. 54.1 ± 15.0 years; p = 0.05), no severe calcification was found in the HF/CA+ group (0.0% vs. 4.5%; p = 0.018). The HF/CA+ group also had fewer ostial lesions (3.4% vs. 15.1%; p = 0.0095) and a higher, albeit not significant, Thrombolysis in Myocardial Infarction frame count (30.4 ± 12.6 vs. 26.6 ± 11 frames; p = 0.06). In the HF/CA+ group, men had a significant number of tandem lesions compared to women (14.5% vs 0.0%, p = 0.02). CONCLUSIONS: Overall, heart failure patients with cardiac amyloidosis were older but were found to have less calcified lesions, less ostial involvement, and a reduced anterograde coronary blood flow. This is the first report examining coronary lesions in heart failure patients with cardiac amyloidosis.

A novel riboswitch classification based on imbalanced sequences achieved by machine learning.

Riboswitch, a part of regulatory mRNA (50-250nt in length), has two main classes: aptamer and expression platform. One of the main challenges raised during the classification of riboswitch is imbalanced data. That is a circumstance in which the records of a sequences of one group are very small compared to the others. Such circumstances lead classifier to ignore minority group and emphasize on majority ones, which results in a skewed classification. We considered sixteen riboswitch families, to be in accord with recent riboswitch classification work, that contain imbalanced sequences. The sequences were split into training and test set using a newly developed pipeline. From 5460 k-mers (k value 1 to 6) produced, 156 features were calculated based on CfsSubsetEval and BestFirst function found in WEKA 3.8. Statistically tested result was significantly difference between balanced and imbalanced sequences (p < 0.05). Besides, each algorithm also showed a significant difference in sensitivity, specificity, accuracy, and macro F-score when used in both groups (p < 0.05). Several k-mers clustered from heat map were discovered to have biological functions and motifs at the different positions like interior loops, terminal loops and helices. They were validated to have a biological function and some are riboswitch motifs. The analysis has discovered the importance of solving the challenges of majority bias analysis and overfitting. Presented results were generalized evaluation of both balanced and imbalanced models, which implies their ability of classifying, to classify novel riboswitches. The Python source code is available at https://github.com/Seasonsling/riboswitch.

Impact of two formulas to calculate percentage diameter stenosis of coronary lesions: from stenosis models (phantom lesion model) to actual clinical lesions.

Percentage diameter stenosis (%DS) by angiography is still commonly used to determine luminal obstruction of coronary artery disease (CAD) lesions. While visual estimation of %DS is widespread, because of high inter-operator variability, quantitative coronary arteriography (QCA) analysis is the gold standard. There are two %DS formulas: %DS1 averages the proximal and distal reference vessel diameter (RVD); %DS2 interpolates the RVD. This study aims to evaluate the difference between %DS assessed by QCA in two datasets, phantom lesion models and CAD patients. Ten phantom lesion models (PLMs) and 354 CAD lesions from the FIRST trial were assessed by QCA. In the latter, two scenarios were assessed: Scenario A (worst view), the most common approach in the clinical setting; and Scenario B (average of two complementary views), the standard core-laboratory analysis. In the PLMs, %DS1 and %DS2 mean ± standard deviation (median) was 58.5 ± 21.7 (61.6) and 58.7 ± 21.6 (61.8), respectively, with a signed difference of - 0.2% ± 0.3% (- 0.1%). In Scenario A, the mean %DS1 was 43.8 ± 9.1 (43.3) and 44.0 ± 9.1 (42 .9) in %DS2. In Scenario B, the mean %DS1 was 45.3 ± 8.8 (45.1) and 45.5 ± 9.0 (45.1) in %DS2. The signed difference was - 0.2% ± 2.4% (0.0%) and - 0.2% ± 2.1% (0.0%) in Scenario A and B, respectively. These differences between formulas ranged from - 1.2 to 0.5% for the phantom cases compared to - 17.7% to 7.7% in Scenario A and to - 15.5% to 7.1% in Scenario B. Although the overall means of the formulas provide similar results, significant lesion-level differences are observed. The use of the worst view versus the average of two views provided similar results.

Effect of Statin Therapy on Fibrous Cap Thickness in Coronary Plaque on Optical Coherence Tomography　- Review and Meta-Analysis.

BACKGROUND: Statin therapy has been shown to result in coronary plaque regression, but the relationship between statin use and stabilization of coronary plaque has not been elucidated. We conducted a systematic review and meta-analysis to evaluate the effect of statin therapy on fibrous cap thickness (FCT) on optical coherence tomography (OCT).Methods and Results:Nine OCT studies (6 randomized controlled trials and 3 observational studies) were enrolled with a total of 341 patients (390 lesions). Arms of the studies were grouped according to statin type and/or dose. Random effects meta-analysis was used to estimate a pooled mean change in FCT from baseline to follow-up. The overall effect mean FCT change was 67.7 µm (95% CI: 51.4-84.1, I2=95.0%, P<0.001). All statin groups had an increase in FCT, but the magnitude of the increase differed according to the statin. Two homogeneous subgroups with I2=0 were identified: mean FCT change was 27.8 µm (for subgroup atorvastatin 5 mg and rosuvastatin), and 61.9 µm (for subgroup atorvastatin 20 mg, fluvastatin 30 mg, and pitavastatin 4 mg). On meta-regression modeling, statin therapy alone explained most of the change in FCT. CONCLUSIONS: Statin therapy induced a significant increase in FCT as assessed on OCT, independent of coronary risk factors and other medications.

Effects of Cangrelor as Adjunct Therapy to Percutaneous Coronary Intervention.

Percutaneous coronary intervention (PCI) in patients with angiographic evidence of intracoronary thrombus is associated with in-hospital and 30-day adverse clinical outcomes. Cangrelor, a direct, rapid-onset acting intravenous P2Y12 receptor inhibitor, has been proved to be effective by reducing peri-PCI ischemic complications in subjects who underwent PCI. This study aimed to assess the angiographic and in-hospital clinical outcomes in all-comer patients receiving cangrelor immediately before PCI at a tertiary care center. The study analyzed consecutive unselected subjects treated with cangrelor at the time the decision was made to proceed with PCI. At the end of the procedure, all patients were transitioned to oral antiplatelet therapy. The target lesion angiographic assessment of Thrombolysis in myocardial infarction flow grade (TIMI-Flow), TIMI-thrombus grade (TIMI-Thrombus), myocardial blush grade, and TIMI-myocardial perfusion grade (TMPG) was performed before and post-PCI. Clinical events were recorded during the procedure and at discharge. In total, 223 patients (244 lesions) were included in the analysis (106, 97, and 20 patientswith TIMI-Flow 0/1, TIMI-Flow 2/3, and cardiogenic shock, respectively). The overall mean age was 63 ± 12 years, 70% men and 38% with diabetes mellitus. Acute myocardial infarction was the main presentation (72%). The use of cangrelor improved TIMI-Flow, MGB, TMPG, and TIMI-Thrombus in patients with initial TIMI-Flow 0 to 2. Major bleeding rate was 2.0%. In conclusion, cangrelor was effective and safe in restoring TIMI-Flow 3, reducing thrombus burden and improving myocardial blush grade and TMPG when administered to unselected subjects who underwent PCI. Therefore, cangrelor should be considered in patients presenting with intracoronary thrombus before intervention.

Clinical outcomes of complete revascularization using either angiography-guided or fractional flow reserve-guided drug-eluting stent implantation in non-culprit vessels in ST elevation myocardial infarction patients: insights from a study based on a systematic review and meta-analysis.

Current guidelines recommend that percutaneous coronary intervention (PCI) should be restricted to the culprit vessel in ST elevation myocardial infarction (STEMI) patients with multi-vessel disease (MVD) and without cardiogenic shock. However, newer data suggests that performing complete revascularization (CR) in MVD patients may lead to better outcomes compared to intervention in the culprit vessel only. The aim of this meta-analysis is to examine the available data to determine if CR (using either angio- or fractional flow reserve guidance-FFR) following primary PCI in STEMI patients without cardiogenic shock impacts clinical outcomes. Meta-analysis was performed by conducting a literature search of PubMed from January 2004 to July 2017. Pooled estimates of outcomes, presented as odds ratios (OR) [95% confidence intervals], were generated using random-effect models. A total of 9 studies (3317 patients) were included. CR showed a significant MACE reduction (OR 0.49, 95% CI 0.36-0.66, p < 0.001); All-cause mortality (OR 0.69, 95% CI 0.48-0.98, p = 0.04) and repeat revascularization (OR 0.38, 95% CI 0.28-0.51, p < 0.001) at ≥ 12 months follow-up. The FFR-guiding CR group presented a MACE reduction (odds ratio 0.52, 95% CI 0.30-0.90, p = 0.02) due to a decrease of repeat revascularization (OR 0.41, 95% CI 0.21-0.80, p = 0.009). Overall, performing complete revascularization in STEMI patients showed a MACE reduction, all-cause death and repeat revascularization. Compared to culprit-only revascularization, treating multi-vessel disease in STEMI patients using FFR guidance is associated with decreased incidence of MACE, due to a decreased rate of revascularization.

Optical coherence tomography-guided percutaneous coronary intervention compared with other imaging guidance: a meta-analysis.

The use of optical coherence tomography (OCT) in PCI guidance is limited perhaps by the lack of adequately powered studies which compare its efficacy and outcomes to the other more popular imaging modalities. We therefore performed a meta-analysis to compare clinical outcomes following OCT-guided PCI with the other imaging modalities in two separate comparisons. We abstracted data from randomized control trials and observational comparative studies focusing on OCT versus either angiography- or IVUS-guided PCI outcomes identified following a systematic search (April 2006 and May 2017). This meta-analysis included a total of 2781 patients; OCT-guidance versus Angiography guidance (n = 1753) and OCT-guidance versus IVUS-guidance (n = 1028). Pooled estimates of outcomes, presented as odds ratios (OR) [95% confidence intervals], were generated with random-effect models. OCT guidance showed lower rates of MACE (OR 0.70 [0.49, 1.00] p = 0.05) and cardiac deaths (OR 0.40 [0.18, 0.90] p = 0.03) compared to Angiography-guidance alone but no statistical significant results for myocardial infarction (OR 0.70 [0.42, 1.16] p = 0.17), stent thrombosis (OR 1.17 [0.40, 3.43] p = 0.77) and target lesion revascularizations (OR 1.07 [0.48, 2.38] p = 0.86).No statistical significance was observed in the OCT versus IVUS comparison; MACE (OR 0.89 [0.46, 1.73] p = 0.73), cardiac deaths (OR 0.56 [0.12, 2.70] p = 0.47), MI (OR 0.56 [0.12, 2.70] p = 0.47), ST (OR 0.43 [0.06, 2.95] p = 0.39), and TLR(OR 0.99 [0.45, 2.18] p = 0.99). OCT-guided PCI in comparison with angiography-guided was associated with reduction in adverse events for the composite of cardiac deaths, myocardial infarction and repeat revascularizations. There was no statistically significant difference in clinical outcomes observed in the comparison between OCT- and IVUS-guidance.

Intravascular ultrasound assessment of the effect of laser energy on the arterial wall during the treatment of femoro-popliteal lesions: a CliRpath excimer laser system to enlarge lumen openings (CELLO) registry study.

The CliRpath Excimer Laser System to Enlarge Lumen Openings (CELLO) registry included patients treated with modified excimer laser catheters for the endovascular treatment of peripheral artery disease affecting the superficial femoral artery (SFA) and proximal popliteal artery. The aim of this study was to assess, via intravascular ultrasound (IVUS) the dissections in the vessel wall following treatment with the laser catheters. IVUS grayscale images from the CELLO registry were systematically reviewed for dissections in the treated vessel segments by two investigators. Images from 33 patients; 66 pullbacks (1867 IVUS frames in 2 phases), were successfully matched frame-to-frame to evaluate identical segments of the treated vessels in the two phases; post-2 mm Turbo-Elite laser pilot channel creation and post Turbo-Booster laser atherectomy. Dissections were categorized as; (1) intimal, (2) medial, (3) intramural hematoma, and (4) adventitial according to the ACC Clinical Expert Consensus Document classification of dissections. An average of 57 frames was evaluated per pullback, giving a total of 3734 frames (1867 matched for pre-ablation (post channel creation) and post-ablation phases). Treatments with the modified Excimer laser catheters resulted in a significant increase in lumen area of 5.5 ± 3.2-mm2 (95% CI 4.3-6.8, p < 0.0001) and reduction in plaque plus media volume of -10.6 ± 36.0 mm3 (95% CI -25.8 to 4.6, p = 0.1619) whilst giving rise to mainly intramural hematoma formations post Turbo-Booster laser treatment in 55% of frames assessed and 24% medial dissections with less than 1% adventitial disruption. The Excimer laser based Turbo-Booster treatment of peripheral artery lesions resulted in significant plaque debulking and increased lumen diameter with negligible degree of adventitial layer injury.