Development and Validation of a Protein Risk Score for Mortality in Heart Failure : A Community Cohort Study.

BACKGROUND: Heart failure (HF) is a complex clinical syndrome with high mortality. Current risk stratification approaches lack precision. High-throughput proteomics could improve risk prediction. Its use in clinical practice to guide the management of patients with HF depends on validation and evidence of clinical benefit. OBJECTIVE: To develop and validate a protein risk score for mortality in patients with HF. DESIGN: Community-based cohort. SETTING: Southeast Minnesota. PARTICIPANTS: Patients with HF enrolled between 2003 and 2012 and followed through 2021. MEASUREMENTS: A total of 7289 plasma proteins in 1351 patients with HF were measured using the SomaScan Assay (SomaLogic). A protein risk score was derived using least absolute shrinkage and selection operator regression and temporal validation in patients enrolled between 2003 and 2007 (development cohort) and 2008 and 2012 (validation cohort). Multivariable Cox regression was used to examine the association between the protein risk score and mortality. The performance of the protein risk score to predict 5-year mortality risk was assessed using calibration plots, decision curves, and relative utility analyses and compared with a clinical model, including the Meta-Analysis Global Group in Chronic Heart Failure mortality risk score and N-terminal pro-B-type natriuretic peptide. RESULTS: The development (n = 855; median age, 78 years; 50% women; 29% with ejection fraction <40%) and validation cohorts (n = 496; median age, 76 years; 45% women; 33% with ejection fraction <40%) were mostly similar. In the development cohort, 38 unique proteins were selected for the protein risk score. Independent of ejection fraction, the protein risk score demonstrated good calibration, reclassified mortality risk particularly at the extremes of the risk distribution, and showed greater clinical utility compared with the clinical model. LIMITATION: Participants were predominantly of European ancestry, potentially limiting the generalizability of the findings to different patient populations. CONCLUSION: Validation of the protein risk score demonstrated good calibration and evidence of predicted benefits to stratify the risk for death in HF superior to that of clinical methods. Further studies are needed to prospectively evaluate the score's performance in diverse populations and determine risk thresholds for interventions. PRIMARY FUNDING SOURCE: Division of Intramural Research at the National Heart, Lung, and Blood Institute of the National Institutes of Health.

Proteomics for heart failure risk stratification: a systematic review.

BACKGROUND: Heart failure (HF) is a complex clinical syndrome with persistently high mortality. High-throughput proteomic technologies offer new opportunities to improve HF risk stratification, but their contribution remains to be clearly defined. We aimed to systematically review prognostic studies using high-throughput proteomics to identify protein signatures associated with HF mortality. METHODS: We searched four databases and two clinical trial registries for articles published from 2012 to 2023. HF proteomics studies measuring high numbers of proteins using aptamer or antibody-based affinity platforms on human plasma or serum with outcomes of all-cause or cardiovascular death were included. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. A third reviewer resolved conflicts. We assessed the risk of bias using the Risk Of Bias In Non-randomized Studies-of Exposure tool. RESULTS: Out of 5131 unique articles identified, nine articles were included in the review. The nine studies were observational; three used the aptamer platform, and six used the antibody platform. We found considerable heterogeneity across studies in measurement panels, HF definitions, ejection fraction categorization, follow-up duration, and outcome definitions, and a lack of risk estimates for most protein associations. Hence, we proceeded with a systematic review rather than a meta-analysis. In two comparable aptamer studies in patients with HF with reduced ejection fraction, 21 proteins were identified in common for the association with all-cause death. Among these, one protein, WAP four-disulfide core domain protein 2 was also reported in an antibody study on HFrEF and for the association with CV death. We proposed standardized reporting criteria to facilitate the interpretation of future studies. CONCLUSIONS: In this systematic review of nine studies evaluating the association of proteomics with mortality in HF, we identified a limited number of proteins common across several studies. Heterogeneity across studies compromised drawing broad inferences, underscoring the importance of standardized approaches to reporting.

Optical coherence tomography assessment of acute thrombogenicity at bifurcation sites using different stenting techniques: A porcine arteriovenous shunt study.

OBJECTIVES: We aimed to compare bare-metal stents (BMS), durable-polymer everolimus-eluting stents (DP-EES), and abluminal biodegradable-polymer sirolimus-eluting stents (ABP-SES) in the bifurcation model setup. BACKGROUND: The mechanism of thrombogenicity, which differs among second-generation stents implanted using double-kissing (DK) crush or culotte stenting techniques, remains unclear. We have shown previously that setting up a porcine arteriovenous shunt model is feasible and useful to assess thrombogenicity at vessel bifurcation points. METHODS: Six porcine shunt models were prepared for the comparison between DK crush and culotte stenting techniques using BMS, DP-EES, and ABP-SES. Intracoronary imaging with high-resolution optical coherence tomography (OCT) was performed to evaluate the thrombogenicity in different stent types in the bifurcation stenting model and was evaluated by a core lab. RESULTS: Culotte stenting demonstrated more thrombogenicity at the proximal main branch (MB) with DP-EES, side branch (SB) with BMS, and the bifurcation site irrespective of the stent type, while DK crush technique exhibited thrombogenicity only at SB with BMS and ABP-SES. OCT analysis revealed malapposition of DP-EES in the proximal MB with culotte stenting. Stent expansion was generally larger in ABP-SES than BMS and DP-EES. CONCLUSIONS: The study provides hypothesis-generating findings in distinct thrombogenicity of bifurcation stenting with DP- or ABP-coated drug-eluting stents.

First in-human evaluation of a novel intravascular ultrasound and optical coherence tomography system for intracoronary imaging.

AIMS: We evaluated the first in-human performance of a novel hybrid imaging catheter that permits simultaneous and co-registered acquisition of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) images. METHODS AND RESULTS: A total of 17 patients undergoing planned percutaneous coronary intervention (PCI) were imaged between August 2018 and August 2019. Eleven patients with both pre- and post-PCI IVUS and OCT images were included in the offline image analysis. IVUS and OCT images were analyzed separately then together with co-registered images for pre-stent findings, and only separately for post-stent findings. A total of 926 frames were analyzed (218 pre-PCI, 708 post-PCI). There was substantial agreement to detect calcific plaque between co-registered IVUS-OCT and standalone IVUS (Kappa 0.72 [0.65-0.79]) and standalone OCT (Kappa 0.75 [0.68-0.81]) while standalone imaging modalities showed lower agreement to detect lipidic and fibrotic plaques compared with co-registered IVUS-OCT. There were more frames with stent underexpansion on IVUS than OCT [72 (28.7%) vs. 58 (23.1%), respectively, p = 0.039]. Detection rates of incomplete stent apposition (present on 20 OCT frames vs. 2 IVUS frames, p < 0.001) and tissue protrusion (40 vs. 27 frames, p < 0.001) were higher on OCT than IVUS. One stent edge dissection was detected in the image analysis and was seen on OCT but not IVUS. All 177 frames with image artifacts contained at least one co-registered imaging modality with interpretable diagnostic content. There were no study device-related adverse events. CONCLUSIONS: Hybrid image acquisition was safe. The availability of both IVUS and OCT changed image interpretation compared to either modality alone, suggesting a complementary role of these two techniques.

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.

Association of Statins With Nonculprit Coronary Lesions and Adverse Events (from the LRP Study).

Intravascular ultrasound and near-infrared spectroscopy can identify vulnerable coronary atherosclerotic plaques. In this LRP (Lipid-Rich Plaque) substudy, we evaluated the association of statins with nonculprit lesion arterial wall lipidic content and subsequent nonculprit major adverse cardiac events. Patients from the LRP study with known statin use were included. We divided the patients into 2 cohorts-"statin therapy" and "statin-naïve"-upon presentation and then described the intravascular ultrasound and near-infrared spectroscopy analysis based on maximum 4-mm lipid core burden index (maxLCBI4mm). At 2-year follow-up, the patients' clinical events were assessed based on their statin regimen change upon discharge. Finally, patients were stratified by statin intensity based on discharge regimen. Among the 1,526 patients, 1,120 were on a statin versus 396 who were statin-naive upon presentation. Patients on a statin at baseline had a statistically higher rate of cardiovascular risk factors, patients who were statin-naive were more likely to present with an acute coronary syndrome, and the maxLCBI4mm did not differ between the 2 groups (315.67 ± 181.36 vs 325.55 ± 192.16; p = 0.359). These findings were consistent in a secondary analysis evaluating statin intensity. Patients who were switched from no statin to a statin had improved outcomes (nonculprit major adverse cardiac events) compared with patients who were on a statin at baseline without change. In conclusion, despite having a higher burden of nonlipid-related cardiac co-morbidities, patients on a statin at baseline had similar maxLCBI4mm with patients who were statin-naive, regardless of intensity. Initiating a statin at discharge provides the most benefit for events related to nonculprit lesions.

Disparities among Black and White patients in plaque burden and composition and long-term impact.

BACKGROUND: Black patients presenting to the catheterization laboratory have more risk factors and worse long-term outcomes. This sub-analysis of the Lipid Rich Plaque (LRP) study quantifies the plaque burden and composition of Black vs White patients and associated outcomes. METHODS: Patients with a singular, self-reported race presenting for cardiac catheterization were enrolled if near-infrared spectroscopy/intravascular ultrasound (NIRS-IVUS) imaging of non-stented, non-culprit (NC) vessels was performed. Lipidic content was quantified at the 4-mm region with maximum Lipid Core Burden Index (maxLCBI4mm). NC major adverse cardiac events (NC-MACE) were defined as: cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization, and hospital readmission for angina with >20 % disease progression through 2 years. RESULTS: Among 1346 patients with a singular, self-reported race, 182 were Black. Black vs White patients were more likely to be female, had higher rates of traditional risk factors, and were more likely to present acutely. Both patients and segments were more likely to have maxLCBI4mm > 400 (46.7 % vs 30.6 %, p < 0.001, respectively; 15.5 % vs 8.9 %, p < 0.001, respectively). Vessel size and plaque burden were larger for Black vs White patients. At 2 years, maxLCBI4mm > 400 and Black race were independently predictive of NC-MACE (hazard ratio [HR] maxLCBI4mm > 400: 2.37 [95 % confidence interval (CI) 1.50-3.76, p < 0.001], Black race: 2.8 [95 % CI 1.27-3.42, p = 0.004], pinteraction = 0.137). CONCLUSIONS: Compared to White patients, Black patients had more lipid-rich plaques with greater plaque burden. Both high lipidic burden and Black race were independently predictive of NC-MACE within 2 years. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02033694, NCT02033694.

Physiologic and compositional coronary artery disease extension in patients with takotsubo syndrome assessed using artificial intelligence: an optical coherence tomography study.

BACKGROUND: Takotsubo syndrome (TTS) is an acute and reversible ventricular motion abnormality without epicardial coronary obstruction. Optical flow ratio (OFR) is an approach to evaluate the coronary stenosis significance based on three-dimensional optical coherence tomography (3D-OCT). The aim of this study is to utilize OCT and an artificial intelligence plaque characterization model to show the prevalence and composition of atherosclerotic disease in coronary vessels of patients with TTS. METHODS: This is a retrospective and observational study which enrolled patients with TTS who underwent coronary angiography and OCT examination. OCT images were analyzed for tissue characterization and OFR computation using a novel artificial intelligence algorithm. RESULTS: A total of 37 patients and 49 vessels were studied. All patients were imaged in the left anterior descending coronary artery (LAD) and about two-thirds were also imaged in the left circumflex coronary artery (LCX). Most patients were women ( n = 35), and apical was the most common takotsubo type. Tissue composition analysis yielded the following overall plaque types: fibrous (67.1%), lipid (15.5%), and calcium (3.77%). The mean OFR for LAD and LCX was 0.97 ± 0.04 and 0.98 ± 0.02, respectively. CONCLUSION: Utilizing automatic plaque characterization on OCT images by artificial intelligence, we found that TTS patients have coronary artery disease (i.e. presence of lipid, calcified, or fibrous tissue). The advent of artificial intelligence methods may allow for large-scale studies of patients with TTS.

Impact of Baseline Imaging of Non-Culprit Coronary Lesions on Adverse Events: Insight From LRP Study.

BACKGROUND/PURPOSE: Intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) can identify vulnerable coronary atherosclerotic plaques. We aimed to compare the presence or absence of baseline intravascular imaging of non-culprit lesions and their subsequent adverse events. METHODS/MATERIALS: We identified patients from the Lipid Rich Plaque (LRP) study who had a non-culprit-lesion adverse event and divided them into 2 cohorts: those with lesions detected with NIRS-IVUS imaging at baseline and those with lesions not imaged at baseline. RESULTS: Overall, 73 patients had an adverse event (99 coronary segments) during the 24-month follow-up period. Among them, 41 patients (56.2%) had a non-culprit-lesion adverse event related to a coronary segment imaged at baseline, and 32 patients (43.8%) had a non-culprit-lesion adverse event adjudicated to a segment that was not scanned at baseline. Angiographic core laboratory analysis suggested that unscanned lesions were more often in the right coronary artery (~50%); branches of the left coronary artery, i.e., diagonal or left obtuse marginal arteries (~20%); smaller vessels; or more tortuous vessels; and less often in the left anterior descending or distal locations. There was a weak trend for acute severe events (adjudicated myocardial infarction and acute coronary syndrome) in patients with lesions not scanned at baseline (50.0% versus 36.6%, p = 0.250). CONCLUSIONS: In patients with follow-up non-culprit-lesion adverse events, nearly half were not imaged with NIRS-IVUS at baseline. Because events related to non-imaged lesions were at least as severe as events related to imaged lesions, future clinical trials and clinical protocols should be designed to minimize this issue. CLINICAL TRIAL REGISTRATION: The Lipid-Rich Plaque Study (LRP), https://clinicaltrials.gov/ct2/show/NCT02033694, NCT02033694.

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.

Predicting future left anterior descending artery events from non-culprit lesions: insights from the Lipid-Rich Plaque study.

AIMS: The left anterior descending (LAD) artery is the most frequently affected site by coronary artery disease. The prospective Lipid Rich Plaque (LRP) study, which enrolled patients undergoing imaging of non-culprits followed over 2 years, reported the successful identification of coronary segments at risk of future events based on near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) lipid signals. We aimed to characterize the plaque events involving the LAD vs. non-LAD segments. METHODS AND RESULTS: LRP enrolled 1563 patients from 2014 to 2016. All adjudicated plaque events defined by the composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization by coronary bypass or percutaneous coronary intervention, and rehospitalization for angina with >20% stenosis progression and reported as non-culprit lesion-related major adverse cardiac events (NC-MACE) were classified by NIRS-IVUS maxLCBI4 mm (maximum 4-mm Lipid Core Burden Index) ≤400 or >400 and association with high-risk-plaque characteristics, plaque burden ≥70%, and minimum lumen area (MLA) ≤4 mm2. Fifty-seven events were recorded with more lipid-rich plaques in the LAD vs. left circumflex and right coronary artery; 12.5% vs. 10.4% vs. 11.3%, P = 0.097. Unequivocally, a maxLCBI4 mm >400 in the LAD was more predictive of NC-MACE [hazard ratio (HR) 4.32, 95% confidence interval (CI) (1.93-9.69); P = 0.0004] vs. [HR 2.56, 95% CI (1.06-6.17); P = 0.0354] in non-LAD segments. MLA ≤4 mm2 within the maxLCBI4 mm was significantly higher in the LAD (34.1% vs. 25.9% vs. 13.7%, P < 0.001). CONCLUSION: Non-culprit lipid-rich segments in the LAD were more frequently associated with plaque-level events. LAD NIRS-IVUS screening may help identify patients requiring intensive surveillance and medical treatment.

Comparison of plaque distribution and wire-free functional assessment in patients with stable angina and non-ST elevation myocardial infarction: an optical coherence tomography and quantitative flow ratio study.

BACKGROUND: Data comparing plaque characteristics and wire-free physiological assessment in the target vessel in patients with stable angina versus acute coronary syndrome are sparse. Therefore, we investigated the difference in plaque distribution between stable angina and non-ST-elevation myocardial infarction (NSTEMI) and explored the relationship between target vessel vulnerability by optical coherence tomography (OCT) and wire-free functional assessment with quantitative flow ratio (QFR). METHODS: Patients with stable angina (n = 25) and NSTEMI (n = 24) were in the final prospective study cohort from the DECODE study (ClinicalTrials.gov, NCT02335086). All 5480 OCT frames in the region of interest were analyzed to study plaque morphology in the target vessel. QFR was analyzed from baseline coronary angiography before percutaneous coronary intervention. Vulnerable vessel score (VVS) was calculated from each plaque, and vessel QFR was then compared. RESULTS: Out of all frames, thin-cap fibroatheroma was common with NSTEMI compared to stable angina (10.9 versus 6.3%, P < 0.01), while fibrous plaque was more commonly seen with stable angina compared to NSTEMI (19.7 versus 14.4%, P < 0.01). Calcified plaque was similar in both clinical settings (approximately 6%). Regression analysis showed that segments with normal vessel walls were located significantly farther from the other plaque types. Longitudinal distances for plaque-type in NSTEMI were numerically greater than those for stable angina; however, the mean difference was less than 10 mm. The VVS had a significant inverse linear correlation with QFR (r = -0.34, P = 0.009). CONCLUSIONS: The plaque distribution by OCT between stable angina and NSTEMI was similar. Target vessel vulnerability was greater in patients with lower QFR value.

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.

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.

Ultra-Short Term Evaluation of Coronary Vessel Wall Changes in Reference Segments Adjacent to Culprit Lesions in ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Culprit lesions of ST-segment elevation myocardial infarction (STEMI) patients are friable, soft, and prone to disruption during primary percutaneous coronary intervention (pPCI). The presence of dissections in reference vessel segments (RVSs), adjacent to stented culprit lesions, and dynamic luminal changes in proximal or distal RVSs have not yet been investigated. We therefore sought to assess the healing patterns of edge dissections and the changes of lumen area at RVSs within 1 week post stent implantation in patients with STEMI. METHODS: In the MATRIX trial (ClinicalTrials.gov NCT01433627), optical coherence tomography (OCT) was performed at the end of pPCI and within 1 week during staged PCI. The RVS dissection was defined as: type 1 = flap; type 2 = cavity; type 3 = double barrel; and type 4 = fissure. We compared separately the fate of residual dissection and luminal area/dimension by OCT in the target vessel between pPCI and staged PCI, including 1-year clinical outcomes. RESULTS: Out of 151 patients, 46 patients had dissections in 50 RVSs and did not experience worse clinical outcome. Dissections were 44% type 1, 28% type 2, 12% type 3, and 16% type 4. Overall, 18% of the dissections healed. The mean lumen area of the RVS enlarged in 82 patients (59%) from pPCI to staged PCI. Compared with the proximal RVS, there was a significant increase in the lumen diameter at the distal RVS (0.06 ± 0.25 mm vs -0.01 ± 0.21 mm; P=.01). CONCLUSION: Dissections occur frequently after pPCI. One-fifth of them heal within 1 week and do not seem to negatively impact clinical outcomes. Distal RVS lumen area increased compared with proximal RVS, likely reflecting a different vasoconstriction pattern over time.

Impact of Endothelial Shear Stress on Absorption Process of Resorbable Magnesium Scaffold: A BIOSOLVE-II Substudy.

BACKGROUND/PURPOSE: Local hemodynamic forces such as endothelial shear stress (ESS) may have an influence on appropriate neointimal healing, vessel remodeling, and struts' absorption process following second-generation drug-eluting resorbable magnesium scaffold (RMS, Magmaris, Biotronik AG, Buelach, Switzerland) placement. The aim of this study was to investigate the impact of ESS assessed by optical coherence tomography (OCT)-based computational fluid dynamic (CFD) simulations on absorption process and coronary lumen dimension after Magmaris implantation. METHODS AND RESULTS: A total of 22 patients who were enrolled in the BIOSOLVE-II trial and underwent serial OCT assessment immediately after Magmaris implantation and at 6- and 12-month follow-up were included. We evaluated qualitative OCT findings frame by frame, and CFD simulations were performed to calculate the ESS at 3-dimensional (3D) reconstructed arteries. For quantitative calculation, the average ESS within each 1-mm section was classified into three groups: low (<1.0 Pa), intermediate (1.0-2.5 Pa), or high (>2.5 Pa). A significant difference of percentage remnants of scaffold was observed among the 3 groups at 12-month follow-up (P = 0.001) but not at 6-month follow-up. Low-ESS segment at baseline resulted in a greater lumen change of -1.857 ± 1.902 mm2 at 1 year compared to -1.277 ± 1.562 mm2 in the intermediate-ESS segment (P = 0.017) and - 0.709 ± 1.213 mm2 in the high-ESS segment (P = 0.001). CONCLUSION: After Magmaris implantation, the presence of higher ESS might be associated with slower strut absorption process but less luminal loss.

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%.

Impact of optical coherence tomography findings on clinical outcomes in ST-segment elevation myocardial infarction patients: a MATRIX (Minimizing Adverse Hemorrhagic Events by Trans-radial Access Site and angioX) OCT sub-study.

PURPOSE: To investigate the association of the degree of stent expansion, as assessed by optical coherence tomography (OCT), following stent implantation, and clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients. METHODS: STEMI patients from the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) OCT study were selected; Clinical outcomes were collected through 1 year. Stent expansion index is a minimum stent area (MSA) divided by average lumen area (average of proximal and distal reference lumen area). The following variables were measured: MSA (< 4.5mm2), dissection (> 200 µm in width and < 5 mm from stent segment), malapposition (> 200 µm distance of stent from vessel wall), a thrombus (area > 5% of lumen area) were compared. RESULTS: A total of 151 patients were included; after excluding patients with suboptimal OCT quality, the population with available OCT was classified into 2 groups: under-expanded < 90% (N = 72, 51%) and well-expanded ≥ 90% (N = 67, 49%). In the well-expanded group, a significant number of the proximal vessels had a lumen area < 4.5mm2 (16.1%, p < 0.001) and a greater thrombus burden within stent (56.7%, p = 0.042). The overall 30 day and 1 year major adverse cardiovascular event (MACE) rates were 5% and 6.1%, respectively. CONCLUSION: Irrespective of the degree of stent expansion, the OCT findings, in STEMI patients, and the MACE at 30 days and one year follow up was low; further, well-expanded stents led to a more significant residual thrombotic burden within the stent but seemed to have insignificant clinical impact. Acknowledged stent optimization criteria, traditionally related to worse outcomes in stable patients, do not seem to be associated with worse outcomes in this STEMI population.

Near-Infrared Spectroscopy Intravascular Ultrasound Imaging: State of the Art.

Acute coronary syndromes (ACS) secondary to coronary vessel plaques represent a major cause of cardiovascular morbidity and mortality worldwide. Advancements in imaging technology over the last 3 decades have continuously enabled the study of coronary plaques via invasive imaging methods like intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The introduction of near-infrared spectroscopy (NIRS) as a modality that could detect the lipid (cholesterol) content of atherosclerotic plaques in the early nineties, opened the potential of studying "vulnerable" or rupture-prone, lipid-rich coronary plaques in ACS patients. Most recently, the ability of NIRS-IVUS to identify patients at risk of future adverse events was shown in a prospective multicenter trial, the Lipid-Rich-plaque Study. Intracoronary NIRS-IVUS imaging offers a unique method of coronary lipid-plaque characterization and could become a valuable clinical diagnostic and treatment monitoring tool.

Feasibility of a Porcine Arteriovenous Shunt Model for Assessment of Acute Thrombogenicity in Bifurcation Stenting Technique By Optical Coherence Tomography.

BACKGROUND: Double kissing (DK) crush stenting has been reported as a superior bifurcation stenting strategy compared to culotte stenting. However, the mechanism associated with the reduction of clinical events by DK crush stenting remains unclear. We therefore investigated the thrombogenicity of DK crush stenting and culotte stenting with both bare-metal stents (BMS) and drug-eluting stents (DES) and the feasibility of a novel porcine arteriovenous shunt model. METHODS: High-resolution intracoronary imaging with optical coherence tomography (OCT) evaluated the bifurcation stenting models for thrombogenicity. RESULTS: All porcine models retained continuous circulation without blood leakage. Thrombus was macroscopically demonstrated around the bifurcation in all settings. The volume of thrombus (mm3) with BMS using DK crush/culotte and DES using DK crush/culotte were 1.38/1.19 and 0.09/0.15, respectively. Culotte stenting had more thrombus in the proximal main branch, and DK crush stenting had more at the bifurcation. Unlike DK crush stenting, culotte stenting showed malapposition in the proximal main branch and bifurcation segments. CONCLUSION: The feasibility of a porcine arteriovenous shunt model to assess thrombogenicity by OCT in bifurcation stenting technique was confirmed. OCT detected less thrombogenicity in DES when used in the bifurcation model when compared to BMS.