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Proteomics offers great promise in improving risk prediction of patients with heart failure. In this community-based cohort study, 7289 plasma proteins were measured in 1351 patients to derive a protein risk score to predict mortality. The study showed that the protein score outperformed clinical risk tools in predicting mortality. Studies to further validate the score and determine risk thresholds for intervention now seem necessary. Visual Abstract. Development and Validation of a Protein Risk Score for Mortality in Heart Failure: Proteomics offers great promise in improving risk prediction of patients with heart failure. In this community-based cohort study, 7289 plasma proteins were measured in 1351 patients to derive a protein risk score to predict mortality. The study showed that the protein score outperformed clinical risk tools in predicting mortality. Studies to further validate the score and determine risk thresholds for intervention now seem necessary. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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%. [ABSTRACT FROM AUTHOR]

Takotsubo syndrome (TTS) is an acute cardiac event without epicardial coronary obstruction but often with reversible ventricular motion abnormalities. Quantitative flow ratio (QFR) is a novel approach to evaluate the coronary stenosis significance on the basis of 3-dimensional quantitative coronary angiography (3D-QCA) and contrast flow by Thrombolysis in Myocardial Infarction frame count. This study aimed to evaluate and compare the QFR value in the left anterior descending artery (LAD) and the left circumflex artery (LCx) in patients with TTS. This retrospective and observational study enrolled 30 patients with TTS who underwent coronary angiography. We evaluated the QFR data using the 3D-QCA analysis and compared the QFR data in the LAD and the LCx. No significant differences were observed in terms of flow velocity, percent diameter stenosis, minimum lumen diameter, and reference diameter between LAD and LCx. However, vessel QFR in the LAD was significantly reduced compared with that in the LCx (0.98 [0.94 to 0.99] vs. 1.00 [0.99 to 1.00], P < 0.001). Ejection fraction at baseline and initial troponin-I levels were not correlated with the vessel QFR both in the LAD and the LCx. The QFR value in the LAD was significantly reduced compared to that in the LCx in patients with TTS. [ABSTRACT FROM AUTHOR]

Aims To compare prolonged bivalirudin infusion vs. an intra-procedural only bivalirudin infusion administration in subjects with ST-segment elevation myocardial infarction (STEMI) regarding residual stent strut thrombosis. Methods and results Multivessel STEMI patients undergoing primary percutaneous coronary intervention (PPCI) and scheduled for a staged percutaneous coronary intervention (PCI) before hospital discharge were selected among those allocated to either prolonged bivalirudin or intra-procedural only bivalirudin infusion in the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) Treatment-Duration study. Optical coherence tomography (OCT) of the infarct-related artery was performed at the end of PPCI and 4–5 days thereafter during staged intervention. The predefined endpoint was the percentage difference in the number of stent cross-sections with a thrombotic area >5% at the end of PPCI and at the time of staged PCI (ΔThCS). Between September 2013 and November 2015, 137 were randomized to either intra-procedural only bivalirudin infusion (N  = 64) or prolonged bivalirudin (N  = 73) at 16 European sites. Mean stent area, minimum lumen area, percentage of malapposed struts, and mean percent thrombotic area were comparable after index or staged PCI. The difference in the proportion of frames with percent thrombotic area >5% (ΔTh > 5%) were −7.7 (−22.1 to 5.1) in the intra-procedural bivalirudin infusion group and −8.8 (−23.1 to 2.6) in the prolonged infusion group (P  = 0.994). Time from index to follow-up OCT imaging and the infarct vessel artery did not affect this OCT-based endpoint. Conclusion A strategy of prolonged bivalirudin infusion after PPCI did not reduce residual stent strut thrombosis when compared with intra-procedural only bivalirudin infusion administration (funded by The Medicines Company and Terumo; MATRIX ClinicalTrials.gov number, NCT01433627). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims  Second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) is an alternative novel device for treating coronary lesions. However, the relationship between in-scaffold dimensions after implantation of DREAMS 2G and vessel healing and luminal results at follow-up is unknown. The aim of this study is, therefore, to investigate whether the expansion index after implantation of DREAMS 2G as assessed by optical coherence tomography (OCT) impacts late luminal status and healing of the vessel wall. Methods and results  This study comprises of a total 65 out of 123 patients who were enrolled in the BIOSOLVE-II trial. We assessed both qualitative and quantitative OCT findings and the expansion index of DREAMS 2G after implantation frame by frame using OCT. Expansion index was defined as minimum scaffold area/mean reference lumen area. The over-expansion group was also defined with expansion index >1.0. The total number of analysed frames at post-procedure and 6-month follow-up was 8243 and 8263 frames, respectively. At 6-month follow-up, in-scaffold healing was documented by the reduction of 82% in dissections, 93% in attached intra-luminal mass (ILM), 65% in non-attached ILM, and 76% in jailed side branch. The over-expansion group had significantly greater in-scaffold luminal volume loss (LVL) compared with the non-over-expansion group [over-expansion: 35.0 (18.5–52.1) mm3 vs. non-over-expansion: 21.0 (11.6–37.9) mm3, P  =   0.039]. Conclusion  Excellent in vivo healing process after implantation of DREAMS 2G was observed at 6 months. We found that higher expansion indices were associated with higher in-scaffold LVL at 6 months assessed by OCT. [ABSTRACT FROM AUTHOR]

Measures of sarcopenia, such as low muscle mass measured from the readily available preoperative computed tomography (CT) images, have been recently suggested as a predictor of outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). However, results of these studies are variable and, therefore, we performed a systematic review of current literature to evaluate sarcopenia as a predictor of outcome post TAVR. The search was carried out in electronic databases between 2008 and 2018. We identified studies that reported CT-derived skeletal muscle area (SMA) and survival outcomes post TAVR. Studies were evaluated for the incidence of early (≤ 30 days) and late all-cause mortality (> 30 days) post TAVR. Eight studies with 1881 patients were included (mean age of 81.8 years ± 12, 55.9% men). Mean body mass index was (28.2 kg/m2 ± 1.1), mean Society of Thoracic Surgeons risk score (7.0 ± 0.6), and mean albumin level was (3.8 g/dL ± 0.1). Higher SMA was associated with lower long-term mortality [odds ratio (OR) 0.49, 95% confidence interval (CI) 0.28-0.83, p = 0.049], compared with low SMA. Also, higher SMA was associated with lower early mortality but was not statistically significant (OR 0.72; 95% CI 0.44-1.18; p = 0.285). CT-derived SMA provides value in predicting post-TAVR long-term outcomes for patients undergoing TAVR. This is a simple risk assessment tool that may help in making treatment decisions and help identifying and targeting high-risk patients with interventions to improve muscle mass prior to and following the procedures. [ABSTRACT FROM AUTHOR]

Deoxyribonucleic acid (DNA) damage and repair signaling cascades are related to the development of atherosclerosis. Pathological studies have demonstrated that healed coronary plaque rupture (HCPR) contributes to plaque progression and predisposes to sudden ischemic cardiac death. The objective of this study is to investigate the relationship between HCPR detected by optical coherence tomography (OCT) and DNA ligase. Forty-two patients with both OCT and DNA ligase were prospectively enrolled. The population included patients with stable angina pectoris (SA) and non-ST-elevation myocardial infarction (NSTEMI). It was found that the prevalence of HCPR was greater in subjects with higher DNA ligase activity (correlation coefficient 0.36, p = 0.019). The presence of HCPR in patients with NSTEMI was greater than in patients with SA per OCT analysis; however, there was no statistical difference in this limited population (22.53% versus 12.83%, respectively, p = 0.116). DNA repair activity by DNA ligase was associated with HCPR in advanced coronary artery plaque by OCT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Takotsubo syndrome (TTS) is an acute cardiac event without epicardial coronary obstruction but often with reversible ventricular motion abnormalities. Quantitative flow ratio (QFR) is a novel approach to evaluate the coronary stenosis significance on the basis of 3-dimensional quantitative coronary angiography (3D-QCA) and contrast flow by Thrombolysis in Myocardial Infarction frame count. This study aimed to evaluate and compare the QFR value in the left anterior descending artery (LAD) and the left circumflex artery (LCx) in patients with TTS. This retrospective and observational study enrolled 30 patients with TTS who underwent coronary angiography. We evaluated the QFR data using the 3D-QCA analysis and compared the QFR data in the LAD and the LCx. No significant differences were observed in terms of flow velocity, percent diameter stenosis, minimum lumen diameter, and reference diameter between LAD and LCx. However, vessel QFR in the LAD was significantly reduced compared with that in the LCx (0.98 [0.94 to 0.99] vs. 1.00 [0.99 to 1.00], P < 0.001). Ejection fraction at baseline and initial troponin-I levels were not correlated with the vessel QFR both in the LAD and the LCx. The QFR value in the LAD was significantly reduced compared to that in the LCx in patients with TTS. [ABSTRACT FROM AUTHOR]