Intermediate Lesions Research Articles

Left anterior velocity reserve by adenosine is not related to angiographic severity of isolated left main stenosis: Potential relevance for revascularization decision making.

Abstract Background Revascularization of asymptomatic left main stenosis (LM) estimated by coronary angiography in the range of ambiguity (40-60%) necessitates further documentation by either intravascular imaging or fractional flow reserve. Distal left anterior descending artery velocity reserve (LADVR) by transthoracic Doppler echo has provided efficient prognostic yield for intermediate LAD lesions. Purpose Aim of the study was to assess the relationship between LADVR and LM stenosis and to evaluate the long-term cardiovascular outcome in patients with intermediate LM stenosis, following decision making for revascularization based on an efficient LADVR, on top of the dobutamine stress echo (DSE) result. Methods Eighty nine asymptomatic patients (age: 67±9 years, men/women: 70/19, ejection fraction EF: 52±6%, follow up: 50±25 months) were selected prospectively. They had an isolated intermediate stable LM stenosis (stenosis range 30-70%, with absence of hemodynamically significant LAD stenosis (<50%) and they were referred for DSE with a concomitant evaluation of LADVR after administration of adenosine. All patients had a negative DSE for ischemia with an estimated LADVR >2. Based on these data revasularization was deferred. Distribution of patients according to % LM stenosis was: LM 30-40%: 55 patients /LM 40-50%: 25 patients /LM50-60%: 6 patients /LM60-70%: 3 patients Results LADVR was not related to age or EF and was similar among LM increments: LM30-40%: 2.9±0.6 vs LM40-50%: 2.6±0.4 vs LM50-60%: 2.8±0.8 (distribution of values: figure1) A negative follow up for cardiac events was available in all patients. Moreover, 45 patients had an additional stress test negative for ischemia (either ECG or DSE/ SPECT) (LM30-40%: 30 patients, LM40-50%: 11patients, LM50-60: 2patients, LM60-70%: 2patients). LADVR was estimated during follow-up in 26±45 patients and it was <2 in 2 patients (both with a new significant LAD stenosis). Changes of LADVR during follow up compared to the initial LADVR were not related to LM stenosis ((% differences: figure2) Conclusion LADVR in the presence of an isolated LM disease is not related to the angiographically estimated stenosis. Moreover, evolution of LADVR is independent of the initial severity of LM stenosis. A negative DSE combined with adenosine LADVR>2 provides an efficient prognostic yield for a safe long-term outcome in isolated LM disease.

WHO classification of melanocytic tumours

The update of the World Health Organisation (WHO) classification of skin tumours has led to new aspects in the classification of melanocytic tumours. Presentation of the classification of melanocytic tumours in light of current clinical, histological and genetic data. Review of the classification of melanocytic neoplasms in the fifth edition of the WHO classification of skin tumours, taking into account current disease concepts. Malignant melanoma is characterised by stepwise tumour progression and is aheterogeneous disease. Benign and intermediate precursor lesions with characteristic driver mutations can be defined for the different melanoma subtypes. Melanocytomas represent agrowing group of intermediate neoplasms which, from agenetic point of view, lie between nevi and melanomas and usually have abenign course. With the update of the WHO classification, genetic parameters are becoming increasingly relevant and shape the terminology. New terms such as 'melanocytoma' require amedical understanding of current disease concepts and good physician-patient communication for appropriate reporting of findings and therapy.

Prognostic Value of Postpercutaneous Coronary Intervention Murray-Law-Based Quantitative Flow Ratio: Post Hoc Analysis From FLAVOUR Trial.

Coronary physiology measured by fractional flow reserve (FFR) is superior to angiography for assessing the efficacy of percutaneous coronary intervention (PCI). Yet, the clinical adoption of post-PCI FFR is limited. Murray law-based quantitative flow ratio (μQFR) may represent a promising alternative, as it can quickly compute FFR from a single angiographic view. The authors aimed to investigate the potential role of post-PCI μQFR in predicting clinical outcomes. This was a post hoc blinded analysis of the FLAVOUR trial. Patients with angiographically intermediate lesions randomized 1:1 to receive FFR or intravascular ultrasound-guided PCI were included. Post-PCI μQFR was assessed in successfully stented vessels, blinded to clinical outcomes. Suboptimal physiological outcome post-PCI was defined a priori as post-PCI μQFR<0.90. The primary endpoint was 2-year target vessel failure, including cardiac death, target vessel myocardial infarction, and target vessel revascularization. Secondary endpoints included the diagnostic concordance of pre-PCI μQFR with FFR in the FFR-guidance arm. Post-PCI μQFR was successfully analyzed in 806 vessels from 777 participants (feasibility 97.0% [806 of 831]). Suboptimal physiological outcome post-PCI was identified in 24.7% (199 of 806) of vessels and post-PCI μQFR<0.90 was associated with higher risk of 2-year target vessel failure (6.1% [12 of 199] vs 2.7% [16 of 607]; HR:2.45 [95%CI: 1.14-5.26]; P = 0.022). Pre-PCI μQFR was obtained in 877 of 919 vessels (feasibility 95.4%), showing 90% accuracy,82% sensitivity, and 94% specificity for identifying physiologically significant stenosis defined by pre-PCIFFR≤0.80. In patients with intermediate lesions who underwent PCI with contemporary imaging or physiology guidance, lower post-PCI μQFR values predict subsequent adverse events. (Fractional FLow Reserve And IVUS for Clinical OUtcomes in Patients With InteRmediate Stenosis [FLAVOUR]; NCT02673424).

Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study.

The Fractional Flow Reserve and Intravascular Ultrasound-Guided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography). The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea. ClinicalTrials.gov Identifier: NCT02673424.

Outcomes of Deferring Percutaneous Coronary Intervention Without Physiologic Assessment for Intermediate Coronary Lesions

Outcomes of Deferring Percutaneous Coronary Intervention Without Physiologic Assessment for Intermediate Coronary Lesions

Quantitative flow ratio of the donor coronary artery supplying a chronic total occlusion territory.

Coronary physiology to guide multi-vessel coronary intervention is associated with better outcome. In the presence of a coronary chronic total occlusion (CTO), hemodynamic evaluation of intermediate lesions in the donor coronary artery supplying a CTO territory still has limitations. We aim to evaluate implementing quantitative flow ratio (QFR) in assessing angiographically intermediate lesions of the main donor coronary artery supplying a CTO territory. We recruited 219 patients with a single main donor vessel to a CTO territory from a single-center CTO registry between 2017 and 2020. Angiographically intermediate coronary lesions of the donor vessels were evaluated using offline QFR before and at a median of 6 months after successful percutaneous coronary intervention (PCI) of CTO. The mean age of the study population was 66.9 ± 11.3 years, and 77.6% were males. Three-vessel disease was documented in 49.8%. The mean QFR value increased significantly in the donor vessels after successful CTO revascularization (0.93 ± 0.062 vs. 0.95 ± 0.046, p < 0.001) and was more prominent in donor vessels with angiographically intermediate stenosis (0.88 ± 0.063 vs. 0.92 ± 0.053, p < 0.001). While the change in QFR was not significant in angiographically normal donor vessel (0.97 ± 0.025 vs. 0.97 ± 0.026, p = 0.814). Fifteen patients had hemodynamically significant stenosis in the donor coronary artery (QFR ≤ 0.80) before CTO-PCI. Among those patients, 40% (n = 6) were turned to be non-significant with QFR > 0.80 after CTO recanalization, and 30% (n = 5) patients remained significant and were treated with PCI. QFR overestimates the severity of intermediate coronary lesions of a donor vessel supplying a CTO territory like other invasive modalities for physiology assessment.

Angiographic Predictors for Repeated Revascularization in Patients with Intermediate Coronary Lesions.

Background: Intermediate lesions (ILs) present challenges in making therapeutic decisions. This study aimed to determine the practical coronary angiographic predictors for revascularization in patients with ILs who underwent repeated angiograms. Methods: This study was a retrospective single-center study. The study subjects were divided into two groups according to their target lesion revascularization (TLR) during the follow-up period: the TLR (+) group (n = 135, 30.9%) and the TLR (-) group (n = 302, 69.1%). We evaluated the angiographic characteristics of ILs such as the presence of branches, luminal irregularity, tortuosity, ulcer/erosion, haziness, and calcification in the ILs, with an average follow-up of 34.2 ± 32.0 months. Results: The TLR (+) group had higher percentage of diameter stenoses (47.3 ± 13.5% vs. 44.2 ± 12.2%, p = 0.006) than the TLR (-) group, whereas the lesion length of the ILs showed no significant differences between the two groups. The prevalence of branches (79.0% vs. 69.1%, p = 0.018) and haziness (4.3% vs. 2.6%, p < 0.001) was higher in the ILs of the TLR (+) group than those of the TLR (-) group. Therefore, the angiographic predictors for the TLR of ILs were haziness (hazard ratio = 2.126, 95% confidence interval = 1.240-3.644, p = 0.006) and % diameter stenosis (DS) ≥ 60% (hazard ratio = 1.025, 95% confidence interval = 1.013-1.037, p < 0.001). Conclusions: Angiographic haziness and % DS > 60% were the independent angiographic predictors for TLR in patients with ILs. Our study is the first to present the angiographic findings of vulnerable plaques of ILs. Further studies such as intravascular imaging or physiologic studies should be strongly considered before making treatment decisions in ILs when such angiographic features are observed.

Comparison of exvivo lesion formation for two adjacent radiofrequency applications with very high-power short-duration in various inter-lesion times.

Very high-power and short-duration (vHPSD) ablation with QDOT MICRO™ facilitates speedy and safe ablation for pulmonary vein isolation. A brief time interval between ablating two neighboring sites with vHPSD may potentially influence the size and geometry of the lesions. This study evaluates lesion formation when delivering adjacent applications using vHPSD at various inter-lesion times (ILTs). Radiofrequency applications were conducted by QDOT MICRO™ catheter with 90 W of strength and 4 s duration. Fresh swine heart tissue on the epicardium was ablated with 10 g of the contact force. Lesions were created using a single application (SA) and double applications (DA) of adjacent lesions with a 6 mm distance between them as measured on the 3D mapping system. The DA was performed with various ILTs, 60 s (DA-60 s), 10 s (DA-10 s), 5 s (DA-5 s), and 0 s (DA-0 s). Out of 90 lesions, 79 were analyzed. Eleven lesions were excluded for one steam pop event, seven out of the target distance, and three divided lesions of two applications. There were no significant differences in surface diameter, cross-sectional diameter, and maximal lesion depth in each application among the groups. The intermediate lesion depth was significantly more profound in groups with shorter and immediate ILT (DA-10, 5, and 0 s) compared to the group with a prolonged ILT between two applications (DA-60 s) (2.99, 3.03, 3.16 mm vs. 2.42 mm, respectively; p < .001). Two adjacent radiofrequency applications with vHPSD in short ILT may result in deeper lesions in the middle of combined double lesions.

Inflammation Biomarker-Driven Vertical Visualization Model for Predicting Long-Term Prognosis in Unstable Angina Pectoris Patients with Angiographically Intermediate Coronary Lesions.

Angina, a prevalent manifestation of coronary artery disease, is primarily associated with inflammation, an established contributor to the pathogenesis of atherosclerosis and acute coronary syndromes (ACS). Various inflammatory markers are employed in clinical practice to predict patient prognosis and optimize clinical decision-making in the management of ACS. This study investigated the prognostic significance of integrating commonly used, easily repeatable inflammatory biomarkers within a multimodal preoperative prediction model in patients presenting with unstable Angina Pectoris (UAP) and intermediate coronary lesions. This retrospective analysis included patients diagnosed with UAP and intermediate coronary lesions (50%-70% stenosis) who underwent coronary angiography at our hospital between January 2019 and June 2021. The assessed outcome was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs). The Boruta algorithm was applied to identify potential risk factors and develop a prognostic multimodal model. A total of 773 patients were enrolled and divided into a training cohort (n=463) and validation cohort (n=310). A nomogram was constructed to predict the probability of MACCE-free survival based on five clinical features: diabetes mellitus, current smoking, history of myocardial infarction, neutrophil-to-lymphocyte ratio, and fasting blood glucose. In the training cohort, the area under the curve values for the nomogram at 24, 32, and 40 months were 0.669, 0.707, and 0.718, respectively, while those in the validation cohort were 0.613, 0.612 and 0.630, respectively. The model demonstrated good calibration in both cohorts with predicted outcomes aligning well with actual results at all time points up to 40 months. Furthermore, decision curve analysis showed significant clinical utility of the model across the specified time intervals. The developed preoperative prognostic model visually illustrates the association among inflammation, blood glucose level, established risk factors, and long-term MACCEs in UAP patients with intermediate coronary lesions.

High-risk plaques in non-culprit lesions and clinical outcome after NSTEMI vs. STEMI.

Complete non-culprit (NC) revascularisation may help reduce recurrent events after non-ST-segment elevation myocardial infarction (NSTEMI), especially if NC lesions would harbour high-risk plaque (HRP) features similar to ST-segment elevation myocardial infarction (STEMI). This study aimed to assess differences in fractional flow reserve (FFR)-negative NC plaque morphology in patients presenting with NSTEMI vs. STEMI and assess the association of HRP morphology and clinical outcome. In the prospective PECTUS-obs study, 438 patients presenting with myocardial infarction (MI) underwent optical coherence tomography (OCT) of all FFR-negative intermediate NC lesions. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE, composite of all-cause mortality, non-fatal MI or unplanned revascularisation) at 2-year follow-up. Four hundred and twenty patients had at least one analysable OCT, including 203 (48.3%) with NSTEMI and 217 (51.7%) with STEMI. The prevalence of HRPs, including thin-cap fibroatheromas, plaque rupture, and thrombus, was comparable between groups. MACE occurred in 29 (14.3%) NSTEMI patients and 16 (7.4%) STEMI patients (Puni-variable = 0.025 and Pmulti-variable = 0.270). Incidence of MACE was numerically higher among patients with HRP, irrespective of the clinical presentation at index (Pinteraction = 0.684). Among HRP criteria, plaque rupture was associated with MACE in both NSTEMI (P < 0.001) and STEMI (P = 0.020). Presence of NC HRP is comparable between NSTEMI and STEMI and leads to numerically higher event rates in both. These results call for additional research on complete revascularisation in NSTEMI and treatment of HRP. NCT03857971.

Is there a gender difference in the effects of cardiovascular risk factors on the anatomical localization and severity of obstruction on coronary arteries?

Abstract Background Whether there is a gender difference in the effects of traditional cardiovascular risk factors(CVRF) on the anatomical localization(AL) and severity(AS) of obstruction on coronary arteries(CA) remains unclear. Purpose In our study, we investigated whether there is a gender difference in the relationship between CVRF and obstruction on CA . Methods We included 978 patients(49.9% women, mean age: 61+10.3) with stable chest pain undergoing invasive coronary angiography between 2019-2021 who were recruited from the database of our clinic. We examined the gender difference in hypertension(HT), diabetes mellitus(DM), smoking, hyperlipidemia, previous history of CAD(H.CAD) and family history of premature CAD(F.CAD) and their correlation with the AL and AS of obstruction on CA in both gender. Results Women were older(p&amp;lt;0.001) with higher rates of HT (p=0.001) and DM(p=0.026) and higher TC, LDLC and HDLC levels respectively (rs) as (p=0.001, p=0.001, p=0.001). Whereas H.CAD and smoking rates were higher in men rs as (p=0.001, p=0.009). The incidence of critical stenosis (≥70 obstruction) &amp; intermediate lesions (50-69%) on all CA and Syntax scores were higher in men(p&amp;lt;0,01). In patients with HT, severe CAD was more prominent on circumflex (Cx)(p=0.029) and right coronary artery(RCA)(p=0.002) in women and on the proximal ( p=0.024) and mid portion of left anterior descending artery(LAD) (p=0.045) in men. In patients with DM a statistically significant(ss) correlation was found between the presence of DM and AS in all vessels except for left main coronary artery (LMCA) in women (LAD prox:p=0.001; LAD mid:p=0.001; diagonal artery(Dg):p=0.003; Cx:p=0.001; RCA:p=0.001 ;LMCA:p&amp;gt;0.05). However no such correlation was observed in men(p&amp;gt;0.05). In patients with H.CAD moderate/severe lesions were more common on proximal(p=0.013) and mid portions of LAD(p=0.021), on CX( p=0.006) and on RCA(p=0.016) in men and more common on the proximal portion of LAD(p=0.047), CX(p=0.014) and RCA(p=0.009) in women. For either smoking and F.CAD there was no such correlation in either gender (p&amp;gt;0,05). As for blood lipid levels no correlation was observed between LDLC, HDLC and triglyceride levels and AL&amp;AS in men(p&amp;gt;0,05). However there was a negative, weak correlation between the HDLC levels and obstruction on LAD mid portion(r=-0.140; p=0.003); on Dg(r=-0.100; p=0.034) on CX (r=-0.154; p=0.001) and on RCA (r=-0.151; p=0.001) in women. Conclusion Major traditional CVRFs have a sex specific impact on AL and AS of obstruction on CA. In the era of precisıon medicine we need gender specific risk scoring systems taking these gender differences into account.

Diagnostic performance of coronary computed tomography angiography for coronary in-stent re-stenosis

Abstract Background Through the development of CT equipment and proper preparation before CT scanning, the accuracy of Coronary computed tomography angiography (CCTA) diagnosis of ischemic heart disease (IHD) is improving, and the role of CCTA in treatment decision is gradually expanding. The latest guidelines recommend CCTA as Class IIa to evaluate stent patency and native vessels in patients with chronic coronary disease. However, diagnostic performance of CCTA to evaluate stent patency in patients who underwent coronary stent was not clarified, respectively the role of CCTA in the evaluation of IHD in native coronary artery was established.. Purpose In the present study, we evaluate the agreement between CCTA and CAG in assessing stent patency in patients with de novo ischemic chest pain who underwent percutaneous coronary intervention (PCI) and evaluated which factors contribute to the differences. Methods From January 1, 2010 to December 31, 2020, we analyzed 845 patients who underwent new CCTA and CAG sequentially for the evaluation of chest pain previously underwent PCI. In CAG and CCTA, ISR is equally defined as a stenosis greater than 50% of the vessel diameter of within the stented segment or its edge (5-mm segments adjacent to the stent). The degree of In-stent restenosis was analyzed by an independently by quantitative coronary angiography (QCA). Results A total of 208 stents were analyzed, the pooled sensitivity and specificity for CCTA on the diagnosis of ISR were 0.78 (0.65-0.89) and 0.93 (0.88-0.96), respectively. LR+ and LR- were 11.19 (6.22-20.15) and 0.23 (0.14-0.39). As a result of analyzing the ISR diagnostic agreement of CCTA by dividing into ACS and CCD group, the agreement of CCTA for ISR diagnosis was relatively low in the ACS group (Sensitivity 0.69 (0.48-0.86) vs. 0.88 (0.69-0.97), specificity 0.92 (0.84-0.97) vs. 0.94 (0.86-0.98), LR+ 9 (4-20.24) vs. 13.9 (5.88-32.88), LR- 0.33 (0.19-0.6) vs. 0.13 (0.04-0.37)) (Table 1). As a result of analyzing related factors in cases of discrepancy in ISR diagnosis, the degree of stenosis in both ACS and CCD groups was mostly intermediate stenosis, which often required additional clinical evaluation (Figure 1). Conclusion When new ischemic chest pain occurred in a patient who previously underwent PCI, the diagnostic accuracy of ISR by CCTA differed depending on the patient’s IHD category. In the CCD group, the diagnostic usefulness of CCTA was comparable both native vessels and ISR, but not in the ACS group. As majority of ISR diagnostic discrepancies were in intermediate lesions, even in the ACS group, CCTA may be considered as a diagnostic tool.

TCT-226 Validation of Coronary Angiography–Based FFR Compared With Pressure Wire–Based FFR to Guide Revascularization of Intermediate Coronary Lesions in Nonculprit Vessels in Patients Presenting With ST-Segment Elevation Myocardial Infarction (FAST STEMI II)

TCT-226 Validation of Coronary Angiography–Based FFR Compared With Pressure Wire–Based FFR to Guide Revascularization of Intermediate Coronary Lesions in Nonculprit Vessels in Patients Presenting With ST-Segment Elevation Myocardial Infarction (FAST STEMI II)

Implementation of a new classification and stratification system for solitary bone tumour: osseous tumour radiological and interpretation and management system.

To propose a histological-grades-based Osseous Tumor Radiological and Interpretation and Management System (OT-RIMS) that would simplify the radiological evaluation of bone tumours, categorize key radiological features into severity levels, and inform corresponding patient management actions. This retrospective study between January 2015 and August 2022 evaluated patients with solitary bone tumours confirmed by pathology and imaging follow-up received 2 or 3 imaging modalities of radiographs, CT, or MRI. Three radiologists independently assessed radiological features, categorized bone lesions based on OT-RIMS criteria, and reached a consensus. Kappa statistics and observed agreement were calculated. A total of 341 patients (mean age, 26.0 years; 159 women) were included, with 102 malignant, 177 benign, and 62 intermediate or low-grade malignant bone lesions. Sensitivity and specificity of readers 1, 2, and 3, respectively, in the identification of malignant tumours into OT-RIMS 4 were 93.1% (95 of 102) and 93.3% (223 of 239), 96.1% (98 of 102) and 91.6% (219 of 239), 92.2% (94 of 102) and 89.5% (214 of 239). Inter-reader agreement of OT-RIMS category for 3 readers was considered excellent (Kendall's W = 0.924, P < .001) with a kappa value of reproducibility in categories 1&2, 3, and 4 of 0.764, 0.528, and 0.930, respectively. The OT-RIMS category demonstrated excellent reproducibility despite the reader's expertise level in categorizing the risk stratification of bone tumours and informing patient management, with histological grades used as the reference standard. The OT-RIMS category reliably stratifies bone tumours into 4 categories corresponding to histological grades and standardized patient management.

Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis.

Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment. We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021. We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions. The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies.

Development of machine learning models for fractional flow reserve prediction in angiographically intermediate coronary lesions.

Fractional flow reserve (FFR) represents the gold standard in guiding the decision to proceed or not with coronary revascularization of angiographically intermediate coronary lesion (AICL). Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. We sought to develop machine learning (ML) models based on clinical, angiographic and OCT variables for predicting FFR. Data from a multicenter, international, pooled analysis of individual patient's level data from published studies assessing FFR and OCT on the same target AICL were collected through a dedicated database to train (n = 351) and validate (n = 151) six two-class supervised ML models employing 25 clinical, angiographic and OCT variables. A total of 502 coronary lesions in 489 patients were included. The AUC of the six ML models ranged from 0.71 to 0.78, whereas the measured F1 score was from 0.70 to 0.75. The ML algorithms showed moderate sensitivity (range: 0.68-0.77) and specificity (range: 0.59-0.69) in detecting patients with a positive or negative FFR. In the sensitivity analysis, using 0.75 as FFR cut-off, we found a higher AUC (0.78-0.86) and a similar F1 score (range: 0.63-0.76). Specifically, the six ML models showed a higher specificity (0.71-0.84), with a similar sensitivity (0.58-0.80) with respect to 0.80 cut-off. ML algorithms derived from clinical, angiographic, and OCT parameters can identify patients with a positive or negative FFR.

Change in Pd/Pa: Clinical Implications for Predicting Future Cardiac Events at Deferred Coronary Lesions.

Cardiovascular events still occur at intermediate stenosis with fractional flow reserve (FFR) ≥0.81, underscoring the additional measure to evaluate this residual risk. A reduction in distal coronary artery pressure/aortic pressure (Pd/Pa) from baseline to hyperemia (ie, change in Pd/Pa) reflects lipidic burden within vessel walls. We hypothesized that this physiological measure might stratify the risk of future cardiac events at deferrable lesions. Lesion- (899 intermediate lesions) and patient-based (899 deferred patients) analyses in those with FFR ≥0.81 were conducted to investigate the association between change in Pd/Pa and target lesion failure (TLF) and major adverse cardiac events at 7 years, respectively. The occurrence of TLF and major adverse cardiac events was 6.7% and 13.4%, respectively. The incidence of target lesion-related nonfatal myocardial infarction was 0.6%. Lesions with TLF had a greater change in Pd/Pa (0.11±0.03 versus 0.09±0.04; P=0.002), larger diameter stenosis (51.0±9.2% versus 46.4±12.4%; P=0.048), and smaller FFR (0.84 [0.82-0.87] versus 0.86 [0.83-0.90]; P=0.02). Change in Pd/Pa (per 0.01 increase) predicted TLF (odds ratio, 1.16 [95% CI, 1.05-1.28]; P=0.002) and major adverse cardiac event (odds ratio, 1.08 [95% CI, 1.01-1.16]; P=0.03). Lesions with change in Pd/Pa ≥0.10 had 2.94- and 1.85-fold greater likelihood of TLF (95% CI, 1.30-6.69; P=0.01) and major adverse cardiac event (95% CI, 1.08-3.17; P=0.03), respectively. Lesions with FFR ≤0.85 had a substantially higher likelihood of TLF when there is a change in Pd/Pa ≥0.10 (12.4% versus 2.9%; hazard ratio, 3.60 [95% CI, 1.01-12.80]; P=0.04). However, change in Pd/Pa did not affect TLF risk in lesions with FFR ≥0.86 (3.8% versus 3.7%; hazard ratio, 0.56 [95% CI, 0.06-5.62]; P=0.62). Despite deferrable FFR values, lesions and patients with a change in Pd/Pa ≥0.10 had higher cardiovascular risk. Change in Pd/Pa might help stratify lesion- and patient-level risks of future cardiac events in those with FFR ≥0.81.

Association of vessel fractional flow reserve (vFFR) with luminal obstruction and plaque characteristics as detected by optical coherence tomography (OCT) in patients with NSTE-ACS: the FAST OCT study.

There is a paucity of data on the performance of angiography-derived vessel fractional flow reserve (vFFR) in coronary artery lesions of patients presenting with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Optical coherence tomography (OCT) allows for visualization of lumen dimensions and plaque integrity with high resolution. The aim of this study was to define the association between vFFR and OCT findings in intermediate coronary artery lesions in patients presenting with NSTE-ACS. The FAST OCT study was a prospective, multicenter, single-arm study. Patients presenting with NSTE-ACS with intermediate to severe coronary artery stenosis in one or multiple vessels with TIMI 3 flow suitable for OCT imaging were eligible. Complete pre-procedural vFFR and OCT data were available in 226 vessels (in 188 patients). A significant association between vFFR and minimal lumen area (MLA) was observed, showing an average decrease of 20.4% (95% CI -23.9% to -16.7%) in MLA per 0.10 decrease in vFFR (adjusted P < 0.001). vFFR ≤ 0.80 showed a sensitivity of 56.7% and specificity of 92.5% to detect MLA ≤ 2.5 mm2. Conversely, vFFR had a poor to moderate discriminative ability to detect plaque instability (sensitivity, 46.9%; specificity, 71.6%). In patients with NSTE-ACS, vFFR is significantly associated with OCT-detected MLA, and vFFR ≤ 0.80 is highly predictive of the presence of significant disease based on OCT. Conversely, the sensitivity of vFFR ≤ 0.80 to detect OCT-assessed significant disease was low, indicating that the presence of significant OCT findings cannot be ruled out based on a negative vFFR.

Validation of angiography-derived Murray law-based quantitative flow reserve (μQFR) against pressure-derived instantaneous wave-free ratio for assessing coronary lesions, a single-center study in Egypt

BackgroundInstantaneous wave-free ratio (iwFR) is a well-validated method for functional evaluation of intermediate coronary lesions. A recently developed Murray law-based QFR (µQFR) allows wire-free FFR estimation using a high-quality single angiographic projection. We aim to determine the diagnostic accuracy of µQFR as compared to wire-based iwFR for physiological assessment of coronary lesions in a sample of Egyptian patients.ResultsOver a one-year period, patients who previously underwent iwFR assessment of an intermediate coronary stenosis (40–90%) were retrospectively included. μQFR analysis was then performed offline using a dedicated artificial intelligence (AI)-aided computation software. All the measurements were performed blinded to iwFR results, and the agreement between iwFR and μQFR values was tested. Forty-nine patients (mean age 57.9 ± 9 years, 72.9% males) were included. Mean value of iwFR and μQFR was 0.90 ± 0.075 and 0.79 ± 0.129, respectively. There was a significant moderate positive linear correlation between μQFR and iwFR (r = 0.47, p = 0.001; 95% CI 0.22–0.68) with moderate-to-substantial agreement between the two methods (Kappa 0.6). In assessing the diagnostic accuracy of μQFR, the receiver operating characteristic (ROC) curve yielded an area under the curve (AUC) of 0.84 (95% CI 0.717–0.962) for predicting functionally significant lesions defined as iwFR < 0.89. The sensitivity and specificity of μQFR < 0.8 for detecting physiological significance of coronary lesions were 89% and 74% with positive and negative predictive values of 70 and 91%, respectively.ConclusionµQFR has good diagnostic accuracy for predicting functionally significant coronary lesions with moderate correlation and agreement with the gold standard iwFR. Angiography-derived µQFR could be a promising tool for improving the utilization of physiology-guided revascularization.

Sex differences in plaque characteristics of fractional flow reserve-negative non-culprit lesions after myocardial infarction

Background and aimsRecurrent events after myocardial infarction (MI) are common and often originate from native non-culprit (NC) lesions that are non-flow limiting. These lesions consequently pose as targets to improve long-term outcome. It is, however, largely unknown whether these lesions differ between sexes. The aim of this study was to assess such potential differences. MethodsFrom the PECTUS-obs study, we assessed sex-related differences in plaque characteristics of fractional flow reserve (FFR)-negative intermediate NC lesions in 420 MI-patients. ResultsAmong the included patients, 80 (19.1 %) were female and 340 (80.9 %) male. Women were older and more frequently had hypertension and diabetes. In total, 494 NC lesions were analyzed. After adjustment for clinical characteristics and accounting for within-patients clustering, lesion length was longer in female patients (20.8 ± 10.0 vs 18.3 ± 8.5 mm, p = 0.048) and minimum lumen area (2.30 ± 1.42 vs 2.78 ± 1.54 mm2, p < 0.001) and minimum lumen diameter (1.39 ± 0.45 vs 1.54 ± 0.44 mm, p < 0.001) were smaller. The minimum fibrous cap thickness was smaller among females (96 ± 53 vs 112 ± 72 μm, p = 0.025), with more lesions harboring a thin cap fibroatheroma (39.3 % vs 24.9 %, p < 0.001). Major adverse cardiovascular events at two years occurred in 6.3 % of female patients and 11.8 % of male patients (p = 0.15). ConclusionsFFR-negative NC lesions after MI harbored more high-risk plaque features in female patients. Although this did not translate into an excess of recurrent events in female patients in this modestly sized cohort, it remains to be investigated whether this difference affects clinical outcome.